ALBERT

All Library Books, journals and Electronic Records Telegrafenberg

feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of computer aided molecular design 8 (1994), S. 709-730 
    ISSN: 1573-4951
    Keywords: Arg-Gly-Asp peptides ; Adhesion antagonista ; Peptide templates ; Conformational restriction ; Vector analysis ; Structure-activity relationships
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary Structurally guided design approaches to low-molecular-weight platelet aggregation antagonists addressing the platelet-associated heterodimeric cell surface receptor gpIIb/IIIa rely on comparative studies of an ensemble of conformationally and biologically characterized compounds, since no high-resolution structure of the receptor system is available. We report a classical indirect and comparative pharmacophore refinement approach based on a series of small cyclic Arg-Gly-Asp (RGD) peptides as gpIIb/IIIa-fibrinogen interaction antagonists. These peptides have previously been investigated as potent and selective tumor cell adhesion inhibitors. The definition of geometrical descriptors classifying the RGD peptide conformations and their subsequent analysis over selected RGD- and RXD-containing protein structures allows for a correlation of distinct structural features for platelet aggregation inhibition. An almost parallel alignment of the Arg and Asp side chains was identified by a vector analysis as being present in all active cyclic hexa-and pentapeptides. This orientation is induced mainly by the constraint of backbone cyclization and is not of any covalent tripeptide-inherent origin, which was rationalized by a 500 ps high-energy MD simulation of a sequentially related linear model peptide. The incorporation of the recognition tripeptide Arg-Gly-Asp into the cyclic peptide templates acted as a filter mechanism, restricting the otherwise free torsional relation of both side chains to a parallel orientation. Based on the derived results, several detailed features of the receptor binding site could be deduced in terms of receptor complementarity. These findings should govern the design of next-generation compounds with enhanced activities. Furthermore, the complementary stereochemical characteristics of the substrate can be used as boundary conditions for pseudoreceptor modelling studies that are capable of reconstructing a hypothetical binding pocket, qualitatively resembling the steric and electronic demands of gpIIb/IIIa. It is interesting to note that these features provide clear differentiation to requirements for inhibition of % MathType!MTEF!2!1!+-% feaafiart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn% hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr% 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq-Jc9% vqaqpepm0xbba9pwe9Q8fs0-yqaqpepae9qq-f0-yqaqVeLsFr0-vr% 0-vr0db8meaabaqaciGacaGaaeqabaWaaeaaeaaakeaacaqGXoWaaS% baaSqaaiaabAfadaWgaaadbaaabeaaaSqabaGccaqGYoWaaSbaaSqa% aiaaiodaaeqaaaaa!3DDC!\[{\text{\alpha }}_{{\text{V}}_{} } {\text{\beta }}_3 \] substrate binding. This can account for the extremely high selectivity and activity of some of our constrained peptides for either the % MathType!MTEF!2!1!+-% feaafiart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn% hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr% 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq-Jc9% vqaqpepm0xbba9pwe9Q8fs0-yqaqpepae9qq-f0-yqaqVeLsFr0-vr% 0-vr0db8meaabaqaciGacaGaaeqabaWaaeaaeaaakeaacaqGXoWaaS% baaSqaaiaab+bbcaqGIbaabeaakiaabk7adaWgaaWcbaGaaG4maaqa% baaaaa!3E56!\[{\text{\alpha }}_{{\text{b}}} {\text{\beta }}_3 \] or the % MathType!MTEF!2!1!+-% feaafiart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn% hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr% 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq-Jc9% vqaqpepm0xbba9pwe9Q8fs0-yqaqpepae9qq-f0-yqaqVeLsFr0-vr% 0-vr0db8meaabaqaciGacaGaaeqabaWaaeaaeaaakeaacaqGXoWaaS% baaSqaaiaabAfaaeqaaOGaaeOSdmaaBaaaleaacaaIZaaabeaaaaa!3DA4!\[{\text{\alpha }}_{\text{V}} {\text{\beta }}_3 \] receptor.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 2
    ISSN: 0009-2940
    Keywords: Arene complexes / Antimony(III) complexes / Organoantimony compounds / Dihydroanthracene ; Chemistry ; Inorganic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Crystals of a 1:2 complex of 9,10-dihydroanthracene and antimony tribromide are obtained from toluene solutions of the components. In the crystal the complex forms corrugated sheets of an inorganic (SbBr3)n coordination polymer, which are cross-linked by antimony coordination to the benzene rings of the dihydroanthracene molecules are also arranged in folded layers. The dihydroanthracene molecules reside on centers of inversion and their carbon skeleton is planar within the limits of the experiment. With contacts from opposite sides of the molecular plane, the dihydroanthracene is η6,(η6)'-coordinated to the Sb(III) centers at distances of 3.25 Å. In a very irregular geometry the coordination sphere of the crystallographically equivalent antimony atoms contains bromine neighbours at different distances. - Antimony trichloride and dihydroanthracene form a complex of ambiguous stoichiometry, while bismuth trichloride again gives a 2;1 complex, the structure of which has not yet been determined.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...