| Autor: |
Eckert, Debra M., Malashkevich, Vladimir N., Hong, Lily H., Carr, Peter A., Kim, Peter S. |
| Jazyk: |
angličtina |
| Předmět: |
|
| Zdroj: |
Cell. (1):103-115 |
| ISSN: |
0092-8674 |
| DOI: |
10.1016/S0092-8674(00)80066-5 |
| Popis: |
The HIV-1 gp41 protein promotes viral entry by mediating the fusion of viral and cellular membranes. A prominent pocket on the surface of a central trimeric coiled coil within gp41 was previously identified as a potential target for drugs that inhibit HIV-1 entry. We designed a peptide, IQN17, which properly presents this pocket. Utilizing IQN17 and mirror-image phage display, we identified cyclic, D-peptide inhibitors of HIV-1 infection that share a sequence motif. A 1.5 Å cocrystal structure of IQN17 in complex with a D-peptide, and NMR studies, show that conserved residues of these inhibitors make intimate contact with the gp41 pocket. Our studies validate the pocket per se as a target for drug development. IQN17 and these D-peptide inhibitors are likely to be useful for development and identification of a new class of orally bioavailable anti-HIV drugs. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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