Quinoxapeptins: novel chromodepsipeptide inhibitors of HIV-1 and HIV-2 reverse transcriptase. I. The producing organism and biological activity

R B Lingham; A H Hsu; J A O'Brien; J M Sigmund; M Sanchez; M M Gagliardi; B K Heimbuch; O Genilloud; I Martin; M T Diez; C F Hirsch; D L Zink; J M Liesch; G E Koch; S E Gartner; G M Garrity; N N Tsou; G M Salituro

doi:10.7164/antibiotics.49.253

Quinoxapeptins: novel chromodepsipeptide inhibitors of HIV-1 and HIV-2 reverse transcriptase. I. The producing organism and biological activity

J Antibiot (Tokyo). 1996 Mar;49(3):253-9. doi: 10.7164/antibiotics.49.253.

Authors

R B Lingham¹, A H Hsu, J A O'Brien, J M Sigmund, M Sanchez, M M Gagliardi, B K Heimbuch, O Genilloud, I Martin, M T Diez, C F Hirsch, D L Zink, J M Liesch, G E Koch, S E Gartner, G M Garrity, N N Tsou, G M Salituro

Affiliation

¹ Merck Research Laboratories, Rahway, NJ 07065, U.S.A.

PMID: 8626240
DOI: 10.7164/antibiotics.49.253

Abstract

Quinoxapeptin A and B are novel chromodepsipeptides which were isolated from a nocardioform actinomycete with indeterminant morphology. Quinoxapeptins A and B are potent inhibitors of HIV-1 and HIV-2 reverse transcriptase and almost equally active against two single mutants forms as well as a double mutant form of HIV-1 reverse transcriptase. Quinoxapeptin A and B are specific inhibitors of HIV-1 and HIV-2 reverse transcriptase because they did not inhibit human DNA polymerase alpha, beta, gamma and delta. Quinoxapeptin A and B are structurally similar to luzopeptin A which was also active against HIV-1 and HIV-2 reverse transcriptase.

Publication types

Comparative Study

MeSH terms

Actinomycetales / classification
Actinomycetales / metabolism
HIV Reverse Transcriptase
HIV-1 / enzymology*
HIV-1 / genetics
HIV-2 / enzymology*
Humans
Hydroxyquinolines / chemistry
Hydroxyquinolines / pharmacology
In Vitro Techniques
Kinetics
Molecular Structure
Mutation
Nucleic Acid Synthesis Inhibitors
Peptides, Cyclic / chemistry
Peptides, Cyclic / metabolism*
Peptides, Cyclic / pharmacology*
Quinoxalines / chemistry
Quinoxalines / metabolism*
Quinoxalines / pharmacology*
RNA-Directed DNA Polymerase / genetics
RNA-Directed DNA Polymerase / metabolism*
Reverse Transcriptase Inhibitors / chemistry
Reverse Transcriptase Inhibitors / metabolism*
Reverse Transcriptase Inhibitors / pharmacology*

Substances

Hydroxyquinolines
Nucleic Acid Synthesis Inhibitors
Peptides, Cyclic
Quinoxalines
Reverse Transcriptase Inhibitors
quinoxapeptin A
quinoxapeptin B
BBM-928 A
reverse transcriptase, Human immunodeficiency virus 2
HIV Reverse Transcriptase
RNA-Directed DNA Polymerase