AIDSWEEKLY Plus; December 9, 2002
Michael Greer, Senior Medical Writer

Bouchaib Bahbouhi and colleagues at Paul Sabatier University in Toulouse, France, the Laboratory of Biochemical Neuroendocrinology in Montreal, and the University of Barcelona investigated the "capacity of synthetic L- and D-peptides encompassing the HIV-1_BRU gp160 REKR cleavage site to interfere with HIV and simian immuno-deficiency virus (SIV) replication and maturation of the envelope glycoprotein (Env) precursors."

An REKR-based D-peptide demonstrated potent antiviral activity and low cytotoxicity, Bahbouhi and coauthors found.

The researchers evaluated the utility of 6 synthetic peptides containing the REKR sequence and up to 11 additional amino acids. Each peptide was constructed with an extra N-terminal decanoyl group for enhanced cell penetration, according to the report.

The D-peptide sequence decTKAKRRVVQREKRV (dec14D) significantly suppressed Env maturation and Env-associated viral activity - including replication and syncytium induction - by HIV-1, HIV-2, and SIV strains. A dec14D variant with an additional C-terminal chloromethane group produced similar results, although truncated versions of the dec14D sequence had no significant antiviral effects, study data showed. With or without the added chloromethane group, dec14D acted by inhibiting the convertase enzyme PC7 (K_i = 4.6 micromoles).

The L-peptide counterpart to dec14D targeted furin, an enzyme similar in function to PC7; however, all of the L-peptides tested were cytotoxic at low doses (Effects of L- and D-REKR amino acid-containing peptides on HIV and SIV envelope glycoprotein precursor maturation and HIV and SIV replication. Biochem J 2002 Sep 15;366(Pt 3):863-72.

"The fact that PC7 and furin are the major prohormone convertases reported to be expressed in T4 lymphocytes, the principal cell targets of HIV, suggests that they are involved in the maturation of HIV and SIV Env precursors," Bahbouhi and colleagues concluded.

The corresponding author for this report is Elmostafa Bahraoui, Laboratoire d'Immuno-Virologie, EA 30-38 Universite Paul Sabatier, UFR/SVT, 118 route de Narbonne 31062, Toulouse, France. E-mail: bahraoui@cict.fr.

A search at www.NewsRx.net using the search term "AIDS and HIV therapy" yielded 1,193 articles in 29 specialized reports.

Key points reported in this study include:

• Synthetic REKR-based peptides can suppress HIV replication

• A 14-amino acid D-peptide containing the REKR sequence inhibited the prohormone convertase PC7

• A similar L-peptide targeted the related enzyme furin, but was cytotoxic at low doses

This article was prepared by AIDS Weekly editors from staff and other reports.

Reference

Bahbouhi B, Chazal N, Seidah NG, et al., "Effects of L- and D-REKR amino acid-containing peptides on HIV and SIV envelope glycoprotein precursor maturation and HIV and SIV replication", Biochem J 2002 Sep 15;366(Pt 3):863-72

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