期刊
VIROLOGY
卷 433, 期 2, 页码 308-319出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2012.08.007
关键词
Feglymycin; Alanine scan; CD4/gp120 inhibitor; CD4 receptor; Gp120; HIV; Resistance; Surface plasmon resonance (SPR)
类别
资金
- KU Leuven (GOA) [10/014, PF/10/018]
- FWO [G.485.08]
- European Commission (CHAARM) [242135, CM0804]
- Dormeur Services Inc.
- Deutsche Forschungsgemeinschaft (DFG) [SU 239/9-1]
- Fonds der Chemischen Industrie
Feglymycin (FGM), a natural Streptomyces-derived 13mer peptide, consistently inhibits HIV replication in the lower mu M range. FGM also inhibits HIV cell-to-cell transfer between HIV-infected T cells and uninfected CD4(+) T cells and the DC-SIGN-mediated viral transfer to CD4(+) T cells. FGM potently interacts with gp120 (X4 and R5) as determined by SPR analysis and shown to act as a gp120/CD4 binding inhibitor. Alanine-scan analysis showed an important role for L-aspartic acid at position 13 for its anti-HIV activity. In vitro generated FGM-resistant HIV-1 IIIB virus (HIV-1 IIIBFGMres) showed two unique mutations in gp120 at positions I153L and K457I. HIV-1 IIIBFGMres virus was equally susceptible to other viral binding/adsorption inhibitors with the exception of dextran sulfate (9-fold resistance) and cyclotriazadisulfonamide (> 15-fold), two well-described compounds that interfere with HIV entry. In conclusion, FGM is a unique prototype lead peptide with potential for further development of more potent anti-HIV derivatives. (C) 2012 Elsevier Inc. All rights reserved.
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