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  • Structure-Activity Relationship  (31)
  • American Association for the Advancement of Science (AAAS)  (31)
  • Annual Reviews
  • Nature Publishing Group
  • 1980-1984  (31)
  • 1983  (14)
  • 1982  (17)
  • 1939
Collection
Keywords
Publisher
  • American Association for the Advancement of Science (AAAS)  (31)
  • Annual Reviews
  • Nature Publishing Group
Years
  • 1980-1984  (31)
Year
  • 1
    Publication Date: 1982-06-11
    Description: Receptors that selectively bind micromolar concentrations of benzodiazepines are present in rat brain membrane. These micromolar receptors exhibit saturable, stereospecific binding, and the potency of benzodiazepine binding to these receptors is correlated with the ability of the benzodiazepines to inhibit maximum electric shock-induced convulsions. Benzodiazepine receptors with nanomolar affinity differ from the micromolar receptors in their binding, kinetic, and pharmacologic characteristics. The micromolar receptors also bind phenytoin, a non-benzodiazepine anticonvulsant. These results provide evidence for a distinct class of clinically relevant benzodiazepine receptors that may regulate neuronal excitability and anticonvulsant activity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bowling, A C -- DeLorenzo, R J -- NS 1352/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1982 Jun 11;216(4551):1247-50.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6281893" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Benzodiazepines/*metabolism/pharmacology ; Benzodiazepinones/metabolism ; Brain/*metabolism ; Calmodulin/antagonists & inhibitors ; Diazepam/metabolism ; Kinetics ; Ligands ; Protein Kinase Inhibitors ; Rats ; Receptors, Drug/*metabolism ; Receptors, GABA-A ; Structure-Activity Relationship
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  • 2
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1982-11-05
    Description: Simple chemical catalysts have been designed to achieve some desirable features of enzymes. These novel catalysts are not proteins, but they may incorporate the typical enzyme catalytic groups and they achieve selectivity in their reactions by use of geometric control, as do enzymes. Catalysts that carry out geometrically controlled chlorinations of aromatic rings and steroids have been constructed. Other catalysts achieve the selective synthesis of amino acids, and still others imitate ribonuclease in detailed mechanism and hydrolyze RNA. Optimization of geometries has led to a rate acceleration of over 10(8) in one instance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Breslow, R -- New York, N.Y. -- Science. 1982 Nov 5;218(4572):532-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7123255" target="_blank"〉PubMed〈/a〉
    Keywords: Catalysis ; Cyclodextrins ; *Enzymes ; Kinetics ; Models, Chemical ; Ribonucleases ; Structure-Activity Relationship ; Substrate Specificity ; Transaminases
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  • 3
    Publication Date: 1982-01-08
    Description: (+/-)-N-Allylnormetazocine is a benzomorphan opioid with psychotomimetic effects. The pure stereoisomers of this compound, as well as the racemic mixture, were compared to phencyclidine for their behavioral effects on squirrel monkeys and rats trained to discriminate phencyclidine from saline. Dose-response determinations were made for responses to phencyclidine, to a racemic mixture of N-allylnormetazocine, and to the pure levo and dextro isomers of N-allylnormetazocine. In both rats and monkeys, the dextro isomer and the racemic mixture produced dose-dependent responses appropriate for phencyclidine; the levo isomer did not produce the responses appropriate for phencyclidine at any of the doses tested. In both species, the levo isomer was more potent than the dextro isomer in decreasing the rate of responding. Thus racemic N-allylnormetazocine is a mixture of compounds that produce different behavioral effects.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brady, K T -- Balster, R L -- May, E L -- DA-00490/DA/NIDA NIH HHS/ -- DA-01442/DA/NIDA NIH HHS/ -- New York, N.Y. -- Science. 1982 Jan 8;215(4529):178-80.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6274022" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Behavior, Animal/*drug effects ; Male ; Naloxone/pharmacology ; Phenazocine/*analogs & derivatives/pharmacology ; Phencyclidine/pharmacology ; Rats ; Rats, Inbred Strains ; Receptors, Opioid/drug effects ; Saimiri ; Stereoisomerism ; Structure-Activity Relationship
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  • 4
    Publication Date: 1982-09-10
    Description: Alkyl-Substituted gamma-butyrolactones were synthesized and tested for their convulsant and anticonvulsant actions in mice and guinea pigs. The alpha-substituted compounds, alpha, alpha-dimethyl-, and alpha-ethyl-alpha-methyl-gamma-butyrolactone were anticonvulsant compounds with a spectrum of activity similar to that of ethosuximide. In contrast, beta-substituted compounds were convulsant agents similar to picrotoxinin. The alpha-substituted-gama-butyrolactones represent a new class of anticonvulsant drug with experimental and clinical potential.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Klunk, W E -- McKeon, A -- Covey, D F -- Ferrendelli, J A -- GM-07200/GM/NIGMS NIH HHS/ -- GM-24483/GM/NIGMS NIH HHS/ -- NS-14834/NS/NINDS NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1982 Sep 10;217(4564):1040-2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6810462" target="_blank"〉PubMed〈/a〉
    Keywords: *4-Butyrolactone/analogs & derivatives/*therapeutic use/toxicity ; Animals ; *Anticonvulsants ; Chemical Phenomena ; Chemistry ; Convulsants ; Drug Evaluation, Preclinical ; Electroencephalography ; Epilepsy, Absence/drug therapy ; Ethosuximide/pharmacology ; *Furans/*therapeutic use ; Guinea Pigs ; Mice ; Structure-Activity Relationship ; Trimethadione/pharmacology
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  • 5
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1982-07-02
    Description: Inosine peripherally administered to rats markedly suppressed spontaneous food intake and food intake induced by diazepam, muscimol, insulin, and food deprivation. The purines 2-deoxyguanosine and 2-deoxyinosine also suppressed food deprivation-induced feeding, whereas 7-methylinosine, which does not bind to the benzodiazepine binding site in vitro, had no effect on food intake when compared with controls. These results suggest that purines may represent endogenous substances that regulate food intake through interactions with the benzodiazepine receptor.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Levine, A S -- Morley, J E -- New York, N.Y. -- Science. 1982 Jul 2;217(4554):77-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7046046" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Appetite/*drug effects ; Deoxyguanosine/pharmacology ; Diazepam/pharmacology ; Eating/*drug effects ; Food Deprivation ; Inosine/analogs & derivatives/pharmacology ; Insulin/pharmacology ; Male ; Muscimol/pharmacology ; Purines/*pharmacology ; Rats ; Rats, Inbred Strains ; Structure-Activity Relationship
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  • 6
    Publication Date: 1982-05-28
    Description: The photosynthesis of previtamin D3 from 7-dehydrocholesterol in human skin was determined after exposure to narrow-band radiation or simulated solar radiation. The optimum wavelengths for the production of previtamin D3 were determined to be between 295 and 300 nanometers. When human skin was exposed to 295-nanometer radiation, up to 65 percent of the original 7-dehydrocholesterol content was converted to previtamin D3. In comparison, when adjacent skin was exposed to simulated solar radiation, the maximum formation of previtamin D3 was about 20 percent. Major differences in the formation of lumisterol3, and tachysterol3 from previtamin D3 were also observed. It is concluded that the spectral character of natural sunlight has a profound effect on the photochemistry of 7-dehydrocholesterol in human skin.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉MacLaughlin, J A -- Anderson, R R -- Holick, M F -- AM 27334/AM/NIADDK NIH HHS/ -- New York, N.Y. -- Science. 1982 May 28;216(4549):1001-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6281884" target="_blank"〉PubMed〈/a〉
    Keywords: Cholecalciferol/*biosynthesis/metabolism ; Dehydrocholesterols/radiation effects ; Ergosterol/metabolism ; Humans ; In Vitro Techniques ; Isomerism ; Photochemistry ; Skin/*metabolism ; Spectrum Analysis ; Structure-Activity Relationship ; Ultraviolet Rays
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  • 7
    Publication Date: 1982-05-07
    Description: Intracerebroventricular administration of oxytocin to virgin female rats that had been ovariectomized and primed with estrogen 48 hours previously induced a rapid onset of full maternal behavior. The maternal behavior persisted and its incidence was dose-related. Tocinoic acid, the ring structure of oxytocin, also rapidly induced the onset of persistent, full maternal behavior. Arginine vasopressin induced persistent maternal behavior, but this behavior had a later onset. Prostaglandin F2 alpha induced strong partial maternal behavior, which showed early onset but did not persist. Many other peptides, ovarian steroids, and prostaglandin E2 were no more effective than saline. These findings suggest that the release of oxytocin and prostaglandin F2 alpha during labor may promote maternal behavior in rats.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pedersen, C A -- Ascher, J A -- Monroe, Y L -- Prange, A J Jr -- MH-22536/MH/NIMH NIH HHS/ -- MH-32316/MH/NIMH NIH HHS/ -- MH-34933/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 1982 May 7;216(4546):648-50.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7071605" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arginine Vasopressin/pharmacology ; Brain/physiology ; Female ; Injections, Intraventricular ; *Maternal Behavior ; Oxytocin/administration & dosage/*pharmacology ; Rats ; Structure-Activity Relationship
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  • 8
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1982-11-12
    Description: Transfer RNA's are probably very strongly selected for translational efficiency. In this article, the argument is presented that the coding performance of the triplet anticodon is enhanced by selection of a matching anticodon loop and stem sequence. the anticodon plus these nearby sequence features (the extended anticodon) therefore contains more coding information than the anticodon alone and can perform more efficiently and accurately at the ribosome. This idea successfully accounts for the relative efficiencies of many transfer RNA's.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yarus, M -- New York, N.Y. -- Science. 1982 Nov 12;218(4573):646-52.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6753149" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Escherichia coli/genetics ; Kinetics ; Nucleic Acid Conformation ; *Protein Biosynthesis ; RNA, Transfer/*genetics ; Ribosomes/metabolism ; Structure-Activity Relationship ; Suppression, Genetic
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  • 9
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1983-11-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kolata, G -- New York, N.Y. -- Science. 1983 Nov 4;222(4623):495-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6623088" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Dna ; Eukaryota/genetics ; Humans ; *Nucleic Acid Conformation ; Species Specificity ; Structure-Activity Relationship
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  • 10
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1983-02-11
    Description: Contrary to previous predictions, relatively short synthetic peptides that mimic part of a protein sequence are routinely capable of eliciting an antiserum that reacts with the partially mimicked protein. Peptides capable of eliciting protein-reactive serums are frequently represented in the primary sequence of a protein, can be characterized by a set of simple chemical rules, and are confined neither to immunodominant regions of intact proteins nor to the amino or carboxyl terminals. As such, synthetic peptide immunogens are valuable for eliciting reagents with predetermined specificity that can be used for basic research. In addition, some synthetic peptides are capable of mimicking regions of virus proteins and eliciting immune responses in animals that are protective against the viral agents. Such peptides may thus serve as the basis for safe, chemically defined synthetic vaccines.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sutcliffe, J G -- Shinnick, T M -- Green, N -- Lerner, R A -- R01 AI 18509/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1983 Feb 11;219(4585):660-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6186024" target="_blank"〉PubMed〈/a〉
    Keywords: *Antibody Specificity ; Cross Reactions ; *Epitopes ; Peptides/immunology ; Proteins/*immunology ; Structure-Activity Relationship ; Vaccines/immunology
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  • 11
    Publication Date: 1983-11-18
    Description: Hybridoma technology has made it possible to introduce into continuous culture normal antibody-forming cells and to obtain large amounts of the immunoglobulin produced by each of these cells. Examination of the structure of a number of monoclonal antibodies that react with a single antigen has provided new information on the structural basis of the specificity and affinity of antibodies. Comparisons of families of monoclonal antibodies derived from a single germ line gene revealed the importance of somatic mutation in generating antibody diversity. Monoclonal antibodies that react with variable regions of other monoclonals allow the further dissection and modulation of the immune response. Finally, the continued somatic instability of immunoglobulin genes in cultured antibody-forming cells makes it possible to determine the rate of somatic mutation and to generate mutant monoclonal antibodies that may be more effective serological reagents.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Teillaud, J L -- Desaymard, C -- Giusti, A M -- Haseltine, B -- Pollock, R R -- Yelton, D E -- Zack, D J -- Scharff, M D -- 5T32GM7288/GM/NIGMS NIH HHS/ -- AI05231/AI/NIAID NIH HHS/ -- AI10702/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1983 Nov 18;222(4625):721-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6356353" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antibodies, Monoclonal/genetics/*immunology ; *Antibody Diversity ; Antibody Specificity ; Genes ; Hybridomas/immunology ; Immunoglobulin Idiotypes/immunology ; Immunoglobulin Variable Region/genetics ; Mice ; Mutation ; Protein Conformation ; Structure-Activity Relationship
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  • 12
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1983-10-28
    Description: Morphological abnormalities including extra compound eyes, extra heads, and distally duplicated legs were generated in cricket embryos by treating eggs with single doses of either benz[g]isoquinoline-5,10-dione or benzo[h]quinoline-5,6-dione. Slight structural modifications of the molecules resulted in a loss of teratogenic activity, although embryotoxicity occurred. These potent insect teratogens can be used for analysis of developmental events during embryogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Walton, B T -- Ho, C -- Ma, C Y -- O'Neill, E G -- Kao, G L -- New York, N.Y. -- Science. 1983 Oct 28;222(4622):422-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6623081" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Isoquinolines/*toxicity ; Orthoptera/*embryology ; Quinolines/*toxicity ; *Quinolones ; Structure-Activity Relationship ; *Teratogens
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  • 13
    Publication Date: 1983-09-30
    Description: Carbocyclic arabinofuranosyladenine (cyclaradine), a novel nucleoside analog with such desired features as hydrolytic and enzymatic stability, adenosine deaminase resistance, and low systemic toxicity, inhibited the replication of herpes simplex virus types 1 and 2. The 5'-methoxyacetate prodrug form exhibited significant efficacy in the topical treatment of genital infections by herpes simplex virus type 2.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vince, R -- Daluge, S -- Lee, H -- Shannon, W M -- Arnett, G -- Schafer, T W -- Nagabhushan, T L -- Reichert, P -- Tsai, H -- CA 23263/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1983 Sep 30;221(4618):1405-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6684328" target="_blank"〉PubMed〈/a〉
    Keywords: Acyclovir/therapeutic use ; Animals ; Disease Models, Animal ; Female ; Guinea Pigs ; Herpes Genitalis/*drug therapy ; Male ; Structure-Activity Relationship ; Vidarabine/*analogs & derivatives/therapeutic use
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  • 14
    Publication Date: 1983-11-11
    Description: Nicarbazin, a drug used to control the protozoal disease coccidiosis in poultry, is a complex of the highly insoluble drug 4,4'-dinitrocarbanilide with 2-hydroxy-4,6-dimethylpyrimidine. The structures of this and other 4,4'-dinitrocarbanilide complexes have not been determined, but an analogous 2:1 complex of 4,4'-dinitrodiphenylamine with 1,4-diacetylpiperazine has been prepared in which the only possible bonds are hydrogen bonds between the amide carbonyls and amino hydrogens. Scanning electron microscopy revealed that micron-size crystals of nicarbazin disintegrate in water to form much smaller dinitrocarbanilide crystals. Similar complex dissolution in the gut of poultry may account for the greater effectiveness of dinitrocarbanilide when administered as complexed rather than uncomplexed drug. Particle size problems associated with other highly insoluble drugs and pesticides may be resolved by the use of nicarbazin-like complexes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rogers, E F -- Brown, R D -- Brown, J E -- Kazazis, D M -- Leanza, W J -- Nichols, J R -- Ostlind, D A -- Rodino, T M -- New York, N.Y. -- Science. 1983 Nov 11;222(4624):630-2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6635662" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Carbanilides/*administration & dosage ; Chickens ; Coccidiostats ; Crystallization ; Intestinal Absorption ; Nicarbazin/*administration & dosage ; Poultry Diseases/*prevention & control ; Solubility ; Structure-Activity Relationship
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  • 15
    Publication Date: 1983-12-16
    Description: Aplysiatoxin and debromoaplysiatoxin, which are isolated from the seaweed, Lyngbya gracilis, differ in their chemical structure only by the presence or absence of a bromine residue in the hydrophilic region. The function and the structure-activity relation of the hydrophilic region are not known. Aplysiatoxin increased malignant transformation, stimulated DNA synthesis, and inhibited the binding of phorbol-12,13-dibutyrate and epidermal growth factor to cell receptors. Debromoaplysiatoxin inhibited the binding of these two substances as strongly as aplysiatoxin but did not increase malignant transformation or stimulate DNA synthesis. These results indicate that a slight change in the chemical structure of the hydrophilic region of aplysiatoxin affects its abilities to increase cell transformation and stimulate DNA synthesis and that the abilities of the tumor promoters to inhibit the binding of phorbol-12,13-dibutyrate and epidermal growth factor are dissociable from their abilities to increase cell transformation and stimulate DNA synthesis under some circumstances.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shimomura, K -- Mullinix, M G -- Kakunaga, T -- Fujiki, H -- Sugimura, T -- New York, N.Y. -- Science. 1983 Dec 16;222(4629):1242-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6316505" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Caenorhabditis elegans Proteins ; Carcinogens/*pharmacology ; Carrier Proteins ; Cell Line ; Cell Transformation, Neoplastic/*drug effects ; Chemical Phenomena ; Chemistry ; DNA/biosynthesis ; Epidermal Growth Factor/metabolism ; Lactones/analysis/*pharmacology ; *Lyngbya Toxins ; Mice ; Phorbol 12,13-Dibutyrate ; Phorbol Esters/metabolism ; *Protein Kinase C ; Receptor, Epidermal Growth Factor ; Receptors, Cell Surface/metabolism ; *Receptors, Drug ; Structure-Activity Relationship
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  • 16
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1982-11-19
    Description: Odors of ten compounds were characterized by approximately 150 subjects who used a list of 146 descriptors. Duplicate profiles correlated highly (P less than .001) and consistently higher than profiles of different odors. Profiles also agreed with those obtained previously. Thus, profiles based on combined responses of many subjects are stable constructs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dravnieks, A -- New York, N.Y. -- Science. 1982 Nov 19;218(4574):799-801.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7134974" target="_blank"〉PubMed〈/a〉
    Keywords: *Alcohols ; Anisoles ; Hexanols ; Humans ; *Odors ; Pyridines ; *Smell ; Structure-Activity Relationship
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  • 17
    Publication Date: 1982-03-26
    Description: Morphine, methadone, meperidine, fentanyl, and clonidine rapidly depressed transmission through sympathetic preganglionic neurons in cats with the spinal cord transected. Naloxone promptly antagonized this effect of the opiates but not that of clonidine which was reversed by alpha 2-adrenergic receptor antagonists. The independent depression of preganglionic neurons by clonidine may contribute to the ability of this drug to depress the symptoms of opiate withdrawal that are characterized by sympathetic hyperactivity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Franz, D N -- Hare, D B -- McCloskey, K L -- GM-07579/GM/NIGMS NIH HHS/ -- HL-24085/HL/NHLBI NIH HHS/ -- RR-05428/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 1982 Mar 26;215(4540):1643-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6280276" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cats ; Clonidine/*pharmacology/therapeutic use ; Evoked Potentials/drug effects ; Humans ; Narcotics/pharmacology ; Receptors, Drug/drug effects ; Reflex/drug effects ; Spinal Cord/cytology ; Structure-Activity Relationship ; Substance Withdrawal Syndrome/*drug therapy ; Sympathetic Nervous System/*drug effects ; Synaptic Transmission/*drug effects
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  • 18
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1982-05-07
    Description: The conformation and dynamics of the d(CGCGAATTCGCG) duplex, its analogs containing mismatched base pairs and helix interruptions, and its complexes with actinomycin and Netropsin, bound separately and simultaneously, have been investigated by nuclear magnetic resonance spectroscopy in aqueous solution. Structural information has been deduced from chemical shift and nuclear Overhauser effect parameters, while the kinetics have been probed from line width and saturation recovery experiments on proton and phosphorus markers at the individual base pair level. These studies lead to an improved understanding of the role of nucleic acid sequence on the structure, flexibility, and conformational interconversions in the duplex state. The nuclear magnetic resonance measurements readily identify helix modification and antibiotic binding sites on the nucleic acid and estimate the extent to which the observed conformational and dynamic perturbations are transmitted to adjacent base pair regions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Patel, D J -- Pardi, A -- Itakura, K -- New York, N.Y. -- Science. 1982 May 7;216(4546):581-90.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6280281" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Dna ; Dactinomycin ; Hydrogen Bonding ; Magnetic Resonance Spectroscopy ; Motion ; Netropsin ; *Nucleic Acid Conformation ; Oligodeoxyribonucleotides ; Protons ; Structure-Activity Relationship ; Temperature
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  • 19
    Publication Date: 1982-10-29
    Description: Saturable and stereospecific binding sites for (+)-[3H]amphetamine were demonstrated in membrane preparations from rat brain. The density of these binding sites varies among brain regions and is highest in the hypothalamus and brainstem. Specific (+)-[3H]amphetamine binding in hypothalamus is largely confined to synaptosomal membranes, rapidly reversible, and sensitive to both heat and proteolytic enzymes. Scatchard analysis of the equilibrium binding data revealed two distinct sites with apparent affinity constants of 93 and 300 nanomoles per liter, respectively. The effects of various psychotropic drugs as well as a number of putative neurotransmitters and related agonists and antagonists in displacing specific (+)-[3H]amphetamine binding demonstrate that these binding sites are not associated with any previously described neurotransmitter or drug receptors, but are specific for amphetamine and related phenylethylamine derivatives. Furthermore, the relative affinities of a series of phenylethylamine derivatives for (+)-[3H]amphetamine binding sites in hypothalamic membranes is highly correlated to their potencies as anorexic agents. These results suggest the presence of specific receptor sites in hypothalamus that mediate the anorexic activity of amphetamine and related drugs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Paul, S M -- Hulihan-Giblin, B -- Skolnick, P -- New York, N.Y. -- Science. 1982 Oct 29;218(4571):487-90.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7123250" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anorexia/physiopathology ; Appetite Depressants/*pharmacology ; Cell Membrane/metabolism ; Dextroamphetamine/*metabolism ; Hypothalamus/drug effects/*metabolism/physiology ; Male ; Phenethylamines/metabolism ; Rats ; Receptors, Drug/*metabolism ; Structure-Activity Relationship
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  • 20
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1982-12-10
    Description: Intracerebroventricular administration of dynorphin produced potent and long-lasting effects on motor function and the electroencephalogram in rats. In addition, local iontophoretic or pressure ejection of dynorphin consistently inhibited hippocampal unit activity. None of these effects were significantly affected by naloxone even at high doses. Moreover, a fragment of dynorphin that failed to displace any of a number of tritiated narcotics from rat brain homogenates produced similar effects on these physiological measures in vivo. On the basis of a variety of criteria for "opiate action," the results suggest that a second biologically active site within the dynorphin sequence is capable of quite potent but nonopiate effects.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Walker, J M -- Moises, H C -- Coy, D H -- Baldrighi, G -- Akil, H -- 1F32DA04183/DA/NIDA NIH HHS/ -- DA02265/DA/NIDA NIH HHS/ -- New York, N.Y. -- Science. 1982 Dec 10;218(4577):1136-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6128791" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Amino Acid Sequence ; Animals ; Dynorphins ; Endorphins/*physiology ; Hippocampus/*physiology ; Male ; Pain/*physiopathology ; Rats ; Structure-Activity Relationship
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  • 21
    Publication Date: 1983-09-23
    Description: A peptide that accumulated as the major product during the proteolysis of arginine vasopressin by rat brain synaptic membranes was isolated and its structure was shown to be the hexapeptide pGlu-Asn-Cys(Cys)-Pro-Arg-Gly-NH2. When administered intracerebroventricularly in extremely low doses, this vasopressin fragment and its desglycinamide derivative facilitated memory consolidation in a passive avoidance situation. These vasopressin metabolites, which are devoid of pressor activity, constitute highly potent neuropeptides with selective effects on memory and related processes; they are activated via proteolytic processing of vasopressin by brain peptidases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Burbach, J P -- Kovacs, G L -- de Wied, D -- van Nispen, J W -- Greven, H M -- New York, N.Y. -- Science. 1983 Sep 23;221(4617):1310-2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6351252" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Arginine Vasopressin/*metabolism/physiology ; Avoidance Learning/physiology ; Brain/*metabolism ; Dose-Response Relationship, Drug ; Male ; Memory/*physiology ; Oligopeptides/metabolism ; Peptide Hydrolases/metabolism ; Rats ; Structure-Activity Relationship
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  • 22
    Publication Date: 1982-02-26
    Description: The glucagon analog [l-N alpha-trinitrophenylhistidine, 12-homoarginine]-glucagon (THG) was examined for its ability to lower blood glucose concentrations in rats made diabetic with streptozotocin. In vitro, THG is a potent antagonist of glucagon activation of the hepatic adenylate cyclase assay system. Intravenous bolus injections of THG caused rapid decreases (20 to 35 percent) of short duration in blood glucose. Continuous infusion of low concentrations of the inhibitor led to larger sustained decreases in blood glucose (30 to 65 percent). These studies demonstrate that a glucagon receptor antagonist can substantially reduce blood glucose levels in diabetic animals without addition of exogenous insulin.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Johnson, D G -- Goebel, C U -- Hruby, V J -- Bregman, M D -- Trivedi, D -- AM21085/AM/NIADDK NIH HHS/ -- AM25318/AM/NIADDK NIH HHS/ -- New York, N.Y. -- Science. 1982 Feb 26;215(4536):1115-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6278587" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Diabetes Mellitus, Experimental/*drug therapy ; Glucagon/*analogs & derivatives/*antagonists & inhibitors/therapeutic use ; Hyperglycemia/*drug therapy ; Male ; Rats ; Receptors, Cell Surface/*drug effects ; Receptors, Glucagon ; Structure-Activity Relationship
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  • 23
    Publication Date: 1982-02-26
    Description: A multineurotransmitter neuronal system that synthesizes and secretes both acetylated and deacetylated forms of alpha-melantropin and beta-endorphin is present in rat and human brain. The N-acetylated from of alpha-melanotropin had more potent behavioral effects than the deacetylated alpha-melanotropin. In the case of beta-endorphin, however, the deacetylated form has been shown to be more potent than the acetylated form. Enzymatic N-acetylation appears to be an important regulatory process for modulating the behavioral activity of peptides secreted from the opiomelanotropinergic multineurotransmitter neuron.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉O'Donohye, T L -- Handelmann, G E -- Miller, R L -- Jacobowitz, D M -- New York, N.Y. -- Science. 1982 Feb 26;215(4536):1125-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7063845" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Animals ; Behavior, Animal/drug effects ; Brain/*metabolism ; Humans ; Melanocyte-Stimulating Hormones/*metabolism/pharmacology ; Neurons/metabolism ; Rats ; Structure-Activity Relationship
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  • 24
    Publication Date: 1982-01-22
    Description: 7-Hydroxymethyl-12-methylbenz[alpha]anthracene (7-HMBA), a carcinogenic major metabolite of 7,12-dimethylbenz[alpha]anthracene (DMBA) in liver, was transformed by liver cytosolic sulfotransferase to reactive 7-HMBA sulfate, which is mutagenic toward Salmonella typhimurium strain TA98. The mutagenicity of 7-HMBA in the presence of hepatic sulfotransferase was much higher than that of DMBA or 7-HMBA in the presence of hepatic monooxygenase.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Watabe, T -- Ishizuka, T -- Isobe, M -- Ozawa, N -- New York, N.Y. -- Science. 1982 Jan 22;215(4531):403-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6800033" target="_blank"〉PubMed〈/a〉
    Keywords: 9,10-Dimethyl-1,2-benzanthracene/analogs & derivatives/*metabolism/pharmacology ; Benz(a)Anthracenes/*metabolism ; Biotransformation ; Mutagenicity Tests ; *Mutagens ; Salmonella typhimurium/drug effects ; Structure-Activity Relationship ; Sulfuric Acids
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  • 25
    Publication Date: 1983-08-26
    Description: Ivermectin is the 22,23-dihydro derivative of avermectin B1, a macrocyclic lactone produced by an actinomycete, Streptomyces avermitilis. It is active at extremely low dosage against a wide variety of nematode and arthropod parasites, apparently by virtue of its action on the mediation of neurotransmission by gamma-aminobutyric acid. It is now in commercial use in various countries for the treatment and control of parasites in cattle, horses, and sheep, and is expected to become available for use in swine and dogs. Since studies with the drug in man are in a preliminary stage, it is not yet known whether ivermectin will be useful in human medicine.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Campbell, W C -- Fisher, M H -- Stapley, E O -- Albers-Schonberg, G -- Jacob, T A -- New York, N.Y. -- Science. 1983 Aug 26;221(4613):823-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6308762" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Anthelmintics ; Arthropods/drug effects ; Humans ; Insecticides/therapeutic use ; Ivermectin ; Lactones/metabolism/pharmacology/*therapeutic use ; Nematode Infections/*drug therapy ; Streptomyces/physiology ; Structure-Activity Relationship ; Synaptic Transmission/drug effects
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  • 26
    Publication Date: 1983-09-30
    Description: The potent alpha-cyano-3-phenoxybenzyl pyrethroids, including cypermethrin, deltamethrin, and fenvalerate, act stereospecifically to inhibit binding to rat brain synaptic membranes of sulfur-35-labeled t-butylbicyclophosphorothionate, a new radioligand for the picrotoxinin binding site. Scatchard analysis indicates that picrotoxinin inhibition of t-butylbicyclophosphorothionate binding is competitive whereas cypermethrin inhibition possibly involves a closely associated site in the gamma-aminobutyric acid receptor-ionophore complex. Studies with 37 pyrethroids reveal an absolute correlation, that is, no false positives or negatives, between mouse intracerebral toxicity and in vitro inhibition: all toxic cyano compounds but none of their nontoxic stereoisomers are inhibitors; cis isomers are more potent than trans isomers as both toxicants and inhibitors; and noncyano pyrethroids are much less potent or are inactive.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lawrence, L J -- Casida, J E -- P01 ES00049/ES/NIEHS NIH HHS/ -- New York, N.Y. -- Science. 1983 Sep 30;221(4618):1399-401.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6310756" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bicyclo Compounds/metabolism ; *Bicyclo Compounds, Heterocyclic ; Binding, Competitive ; Brain/metabolism ; Insecticides/*pharmacology ; Ionophores/antagonists & inhibitors ; Picrotoxin/metabolism ; Protein Binding ; Pyrethrins/metabolism/*pharmacology ; Rats ; Receptors, Cell Surface/*drug effects/metabolism ; Receptors, GABA-A ; Stereoisomerism ; Structure-Activity Relationship ; Synaptic Membranes/metabolism
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  • 27
    Publication Date: 1983-03-04
    Description: Six structural homologs of spermidine and five of its precursor, putrescine, were studied for their ability to prevent cytostasis of cultured L1210 leukemia cells induced by alpha-difluoromethylornithine (DFMO), a specific inhibitor of putrescine biosynthesis. High-performance liquid chromatography and competition studies with spermidine indicated that the homologs, which vary in the length of the carbon chain separating the amines, penetrated the cells. The structural specificity of the spermidine carrier was defined. Three of the six spermidine homologs supported cell growth during a 48-hour incubation in the presence of DFMO, indicating that a two-carbon extension of spermidine structure was tolerated for biological function. Two of the five putrescine homologs supported growth after being converted by the cells to their respective spermidine homologs. The central nitrogen of spermidine appears to be essential for function since diamines of chain length comparable to that of spermidine did not prevent DFMO cytostasis. No more than 15 percent of the spermidine normally present in L1210 cells was required for cell proliferation in the presence of DFMO.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Porter, C W -- Bergeron, R J -- CA-22153/CA/NCI NIH HHS/ -- CA-24538/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1983 Mar 4;219(4588):1083-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6823570" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Division ; *Cell Physiological Phenomena ; Eukaryotic Cells/*physiology ; Leukemia L1210/pathology ; Mice ; Ornithine Decarboxylase Inhibitors ; Putrescine/physiology ; Spermidine/analogs & derivatives/*physiology ; Structure-Activity Relationship
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  • 28
    Publication Date: 1982-01-01
    Description: Extended analogs of adenosine triphosphate (ATP) and guanosine triphosphate (GTP), in which a peroxide bridge replaces the terminal bridge-oxygen of the triphosphate chain, have been synthesized. The ability of beta, gamma-peroxy-ATP to inhibit or substitute for ATP in representative enzyme systems and that of beta, gamma-peroxy-GTP, for FTP in protein synthesis was tested.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rosendahl, M S -- Leonard, N J -- GM-05829/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1982 Jan 1;215(4528):81-2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7053563" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/*analogs & derivatives/chemical synthesis/metabolism ; Guanosine Triphosphate/*analogs & derivatives/chemical synthesis/metabolism ; Kinetics ; Peroxides ; Protein Biosynthesis/drug effects ; Structure-Activity Relationship
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  • 29
    Publication Date: 1983-08-19
    Description: Heparin or a heparin fragment administered with cortisone inhibited angiogenesis, caused regression of large tumor masses, and prevented metastases. Oral administration of heparin resulted in the release of non-anticoagulant heparin fragments in the serum which, in the presence of cortisone, had similar anti-angiogenic and antitumor effects. Of all the heparin fragments tested, the most potent inhibition of angiogenesis in the presence of cortisone was provided by a hexasaccharide with a molecular weight of about 1600.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Folkman, J -- Langer, R -- Linhardt, R J -- Haudenschild, C -- Taylor, S -- EY04002/EY/NEI NIH HHS/ -- GM25810/GM/NIGMS NIH HHS/ -- R01-CA14019/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1983 Aug 19;221(4612):719-25.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6192498" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Antineoplastic Agents ; Chick Embryo ; Cortisone/*pharmacology ; Heparin/*pharmacology ; Inflammation ; Neoplasm Metastasis ; Neoplasms, Experimental/blood supply ; Neovascularization, Pathologic/*physiopathology ; Oligosaccharides/pharmacology ; Rabbits ; Structure-Activity Relationship
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  • 30
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1983-04-22
    Description: The inactive methadone analog threo-5-methylmethadone has a solid-state conformation in which the nitrogen is antiperiplanar to the tertiary carbon C(4). Since threo-5-methylmethadone exhibits no opioid agonism either in vivo or in vitro, methadone analogs probably do not have this conformation when bound to an opioid receptor. The potent agonist (-)-erythro-5-methylmethadone has a solid-state conformation in which the nitrogen atom is rotated back toward the phenyl rings on the quarternary carbon, suggesting that this unusual conformation is the active one.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Duax, W L -- Smith, G D -- Griffin, J F -- Portoghese, P S -- RR-05716/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 1983 Apr 22;220(4595):417-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6301007" target="_blank"〉PubMed〈/a〉
    Keywords: Methadone/analogs & derivatives/*pharmacology ; Molecular Conformation ; Receptors, Opioid/metabolism ; Stereoisomerism ; Structure-Activity Relationship
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  • 31
    Publication Date: 1983-11-18
    Description: Three mutations of the enzyme dihydrofolate reductase were constructed by oligonucleotide-directed mutagenesis of the cloned Escherichia coli gene. The mutations--at residue 27, aspartic acid replaced with asparagine; at residue 39, proline replaced with cysteine; and at residue 95, glycine replaced with alanine--were designed to answer questions about the relations between molecular structure and function that were raised by the x-ray crystal structures. Properties of the mutant proteins show that Asp-27 is important for catalysis and that perturbation of the local structure at a conserved cis peptide bond following Gly-95 abolishes activity. Substitution of cysteine for proline at residue 39 results in the appearance of new forms of the enzyme that correspond to various oxidation states of the cysteine. One of these forms probably represents a species cross-linked by an intrachain disulfide bridge between the cysteine at position 85 and the new cysteine at position 39.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Villafranca, J E -- Howell, E E -- Voet, D H -- Strobel, M S -- Ogden, R C -- Abelson, J N -- Kraut, J -- CA17374/CA/NCI NIH HHS/ -- F32 GM09375/GM/NIGMS NIH HHS/ -- GM10928/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1983 Nov 18;222(4625):782-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6356360" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Disulfides ; Escherichia coli/genetics ; Gene Expression Regulation ; Genes ; Genes, Bacterial ; *Mutation ; Structure-Activity Relationship ; Tetrahydrofolate Dehydrogenase/*genetics
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