Nakajima H, Schramm HJ, Schramm W, Wakayama E, Yamamoto N; International Conference on AIDS.
Int Conf AIDS. 1991 Jun 16-21; 7: 112 (abstract no. W.A.1083).
Yamaguchi University, Yamaguchi, Japan
OBJECTIVE: Active HIV PR consists of two identical subunits. The prevention of dimerization of the subunits or the labilization of the dimer structure by suitable agents should yield a very selective inhibition of PR. Since the homodimer is mainly connected by a four-stranded antiparallel beta sheet formed by the 2 N termini and the 2 C termini, two synthetic peptides derived from the N and C terminus, respectively, were tested for inhibitory activity against HIV-1. METHODS: The two octapeptides were kindly supplied by Green Cross Company (Osaka, Japan); Ia = Ac-Q-I-G-M-T-L-N-F-OH (92-99), Ib = Ac-P-Q-I-T-L-W-Q-R-OH (1-18). The inhibitory activity was assayed according to Pauwels et al. The cell line was MT-4, the HIV strain III(B). RESULTS AND CONCLUSIONS: Weak inhibitory activity of Ia and Ib was observed, comparing with AZT or dextran sulfate. The 50% effective dose ED50 (mug/ml) was 27.5 for Ia and 64.5 for Ib (for comparison: dextran sulfate ED50 = 2.47 mug/ml). The cytotoxicity (50% cytotoxic dose CD50 = greater than 200 mug/ml) against uninfected cells could not be tested above 200 mug/ml because of low solubility. Although the inhibition is low, the results confirm the value of the approach. Dimerization inhibitors of HIV PR might also act on other homologous retroviral proteases. More peptides are being synthesized and tested.
Publication Types:
Keywords:
- Chromosomes
- Dimerization
- Endopeptidases
- HIV Protease
- HIV Protease Inhibitors
- HIV-1
- Japan
- Peptides
- genetics
Other ID:
UI: 102192275
From Meeting Abstracts