Identification of a D-amino acid decapeptide HIV-1 entry inhibitor

Journal Article · Fri Sep 08 04:00:00 EDT 2006 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2006.06.150· OSTI ID:20854447

Boggiano, Cesar ^[1]; Shibo, Jiang ^[2]; Hong, Lu ^[2]; Qian, Zhao ^[2]; Shuwen, Liu ^[2]; Binley, James ^[1]; Blondelle, Sylvie E ^[1]

---

1. Torrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San Diego, CA 92121 (United States)
2. Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10021 (United States)

Entry of human immunodeficiency virus type 1 (HIV-1) virion into host cells involves three major steps, each being a potential target for the development of entry inhibitors: gp120 binding to CD4, gp120-CD4 complex interacting with a coreceptor, and gp41 refolding to form a six-helix bundle. Using a D-amino acid decapeptide combinatorial library, we identified peptide DC13 as having potent HIV-1 fusion inhibitory activity, and effectively inhibiting infection by several laboratory-adapted and primary HIV-1 strains. While DC13 did not block binding of gp120 to CD4, nor disrupt the gp41 six-helix bundle formation, it effectively blocked the binding of an anti-CXCR4 monoclonal antibody and chemokine SDF-1{alpha} to CXCR4-expressing cells. However, because R5-using primary viruses were also neutralized, the antiviral activity of DC13 implies additional mode(s) of action. These results suggest that DC13 is a useful HIV-1 coreceptor antagonist for CXCR4 and, due to its biostability and simplicity, may be of value for developing a new class of HIV-1 entry inhibitors.

• OSTI ID: 20854447
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 4 Vol. 347; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AIDS
AIDS VIRUS
AMINO ACIDS
IMMUNITY
MONOCLONAL ANTIBODIES
PEPTIDES