Publication Date:
1993-03-12
Description:
This article summarizes methods for the synthesis of phosphorodithioate-linked deoxyoligonucleotides and details an analysis of one of the distinctive properties of phosphorodithioate DNA oligomers, their ability to strongly inhibit human immunodeficiency virus type-1 reverse transcriptase (HIV-1 RT). Mechanistic studies indicate that oligomers of this type interfere with enzyme function by binding tightly to the active site for primer-template, which results in low or subnanomolar inhibitory constants. Although many of these studies have used deoxyoligocytidine analogs, a rationally designed approach has led to the discovery of a very active phosphorodithioate deoxyoligonucleotide inhibitor. This type of inhibitor, which binds strongly to the primer-template active site of HIV-1 RT, provides another type of potential therapeutic agent against HIV-1.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marshall, W S -- Caruthers, M H -- GM21120/GM/NIGMS NIH HHS/ -- GM25680/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1993 Mar 12;259(5101):1564-70.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Biochemistry, University of Colorado, Boulder 80309.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7681216" target="_blank"〉PubMed〈/a〉
Keywords:
Antiviral Agents/*chemical synthesis/pharmacology
;
Base Sequence
;
HIV Reverse Transcriptase
;
HIV-1/drug effects/*enzymology
;
Kinetics
;
Molecular Sequence Data
;
Oligodeoxyribonucleotides/*chemical synthesis/pharmacology
;
Organothiophosphates/*chemical synthesis/pharmacology
;
*Reverse Transcriptase Inhibitors
;
Structure-Activity Relationship
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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