Differential inhibition of polymerase and strand-transfer activities of HIV-1 reverse transcriptase.
A new class of inhibitors of HIV-1 reverse transcriptase obtained by the systematic structural simplification of epicatechin and epigallocatechin gallates are also shown here to inhibit DNA-strand-transfer, a process critical to the completion of the HIV-1-RT reproduction and to recombination-associated mutation of the virus. Up to 80-fold selectivity for DNA-strand-transfer inhibition over polymerase inhibition was observed for a defined subset of these agents. Such specific DNA-strand-transfer inhibitors may have important therapeutic potential.
Tillekeratne
L M Viranga
LM
Department of Medicinal and Biological Chemistry, College of Pharmacy, University of Toledo, Toledo, OH 43606, USA.
Sherette
Angela
A
Fulmer
Jennifer A
JA
Hupe
Lynn
L
Hupe
Donald
D
Gabbara
Sam
S
Peliska
James A
JA
Hudson
Richard A
RA
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002392:Catechin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D004277:DNA, Single-Stranded / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D016914:Ribonuclease H / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
D019380:Anti-HIV Agents; D004277:DNA, Single-Stranded; D005707:Gallic Acid; D002392:Catechin; D054303:HIV Reverse Transcriptase; D016914:Ribonuclease H; C057580:gallocatechol