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Abstract
SMALL l- AND d-AMINO ACID PEPTIDES ANTAGONIZE HIV-1 REPLICATION
C. Boggiano, S.B. Blondelle
Torrey Pines Institute for Molecular Studies, San Diego, CA, USA
A number of reports have now not only demonstrated the potential of HIV-1 peptide antagonists as drug candidates, but also the flexibility of peptides to specifically antagonize separate steps of HIV-1 life cycle. In particular, clinical trials have shown that the 36-amino acid long peptide T20, corresponding to a region of HIV-1 glycoprotein gp41, reduces HIV-1 viremia to undetectable levels. Using synthetic peptide combinatorial libraries, we have identified novel l-amino acid nonapeptides that inhibit HIV-1 replication with IC50 values ranging from 0.4 to 10ÁM. Inhibition of replication was observed for both X4 and R5 viruses, including a AZT-resistant clinical isolate. Since d-peptides, by their nature, are much more stable to proteolysis and are attractive alternate drug candidates to natural l-peptides, a library of d-amino acid decapeptides was also screened for inhibition of HIV-1 replication. Individual d-amino acid decapeptides were identified from this library, which inhibit HIV-1 replication with IC50 values ranging from 1 to 10ÁM. Inhibitory specificity to HIV-1 entry was demonstrated using pseudotyped non-competent replication viruses. Interestingly, a common motif from the C-terminal region of gp41 was found in a number of the active peptides. Elucidation of the peptides mechanisms and/or sites of inhibition was initiated by means of circular dichroism spectroscopy, flow cytometry, and luciferase-based assays. The identification of the peptides as well as the evaluation of their biological effects and mechanisms will be presented.
The 2nd IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
525
Suggested Citation
" C. Boggiano, et al.
SMALL l- AND d-AMINO ACID PEPTIDES ANTAGONIZE HIV-1 REPLICATION.
Poster:
The 2nd IAS Conference on HIV Pathogenesis and Treatment:
Abstract no.
525"
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