The Journal of Antibiotics
Online ISSN : 1881-1469
Print ISSN : 0021-8820
ISSN-L : 0021-8820
L-696, 474, A NOVEL CYTOCHALASIN AS AN INHIBITOR OF HIV-1 PROTEASE
III. BIOLOGICAL ACTIVITY
RUSSELL B. LINGHAMAMY HSUKEITH C. SILVERMANGERALD F. BILLSANNE DOMBROWSKIMARK E. GOLDMANPAUL L. DARKELEE HUANGGREGORY KOCHJOHN G. ONDEYKAMICHAEL A. GOETZ
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1992 Volume 45 Issue 5 Pages 686-691

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Abstract

L-696, 474, an inhibitor of the HIV-1 protease, was discovered in extracts of the fungal culture Hypoxylon fragiforme (MF5511; ATCC 20995). L-696, 474 is a novel cytochalasin with a molecular weight of 411 and an empirical formula of C30H39NO4. L-696, 474 inhibited HIV-1 protease activity with an IC50 of 3μM and the mode of inhibition was competitive with respect to substrate (apparent Ki=1μM). Furthermore, L-696, 474 was not a slow-binding inhibitor. The inhibition due to L-696, 474 was also independent of the HIV-1 protease concentration. L-696, 474 was inactive against pepsin, another aspartyl protease; stromelysin, a zinc-metalloproteinase; papain, a cysteine-specific protease or human leucocyte elastase, a serine-specific protease. Two other novel cytochalasins (L-697, 318 and L-696, 475) isolated from the same culture were inactive against the HIV-1 protease. Commercially available cytochalasins B, C, D, E, F, H and J were inactive while cytochalasin A was as active as L-696, 474 against the HIV-1 protease.

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© Japan Antibiotics Research Association
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