HIV-1 resistance mechanism to an electrostatically constrained peptide fusion inhibitor that is active against T-20-resistant strains
| Autor: | Kentaro Watanabe, Kazuya Shimura, Yasuko Sakagami, Mitsuo Kaku, Fusako Miyamoto, Kazuki Shimane, Nobutaka Fujii, Stefan G. Sarafianos, Shinya Oishi, Kumi Kawaji, Eiichi Kodama, Masao Matsuoka |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Enfuvirtide
Lysine Molecular Sequence Data Static Electricity Glutamic Acid Peptide Biology Gp41 Antiviral Agents Protein Structure Secondary HIV Fusion Inhibitors Cell Line Tumor Static electricity Drug Resistance Viral medicine Humans Pharmacology (medical) Amino Acid Sequence Peptide sequence Pharmacology chemistry.chemical_classification Fusion Glutamic acid HIV Envelope Protein gp41 Peptide Fragments Infectious Diseases Biochemistry chemistry Amino Acid Substitution HIV-1 medicine.drug |
| Zdroj: | Antimicrobial agents and chemotherapy. 57(8) |
| ISSN: | 1098-6596 |
| Popis: | T-20EK is a novel fusion inhibitor designed to have enhanced α-helicity over T-20 (enfuvirtide) through engineered electrostatic interactions between glutamic acid (E) and lysine (K) substitutions. T-20EK efficiently suppresses wild-type and T-20-resistant variants. Here, we selected T-20EK-resistant variants. A combination of L33S and N43K substitutions in gp41 were required for high resistance to T-20EK. While these substitutions also caused resistance to T-20, they did not cause cross-resistance to other known fusion inhibitors. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|