Glycosylated enfuvirtide: a long-lasting glycopeptide with potent anti-HIV activity.
J Med Chem
; 58(3): 1372-9, 2015 Feb 12.
Article
en En
| MEDLINE
| ID: mdl-25594223
ABSTRACT
Many peptide-based therapeutics have short circulatory half-lives. We report here that the pharmacokinetics of an anti-HIV peptide drug enfuvirtide (ENF) can be dramatically improved by a chemical glycosylation approach. A set of glycosylated ENFs with varying glycosylation sites and glycan structures were synthesized. Among these, a sialic acid-introduced peptide (SL-ENF) demonstrated a 15-fold extended half-life in rats relative to ENF (T1/2 23.1 vs 1.5 h), and its antiviral potency was comparable to that of ENF (EC50 2 vs 3 nM). SL-ENF bound to a functional fragment of the HIV fusogenic protein gp41 and formed complexes with high affinity and α-helicity, revealing the mechanism behind its potent antiviral activity. Because it is widely accepted in biology that glycosylation protects proteins from denaturation and proteases, our approach may be useful for the development of novel protein and peptide drugs with enhanced pharmaceutical properties.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fragmentos de Péptidos
/
Glicopéptidos
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Proteína gp41 de Envoltorio del VIH
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VIH
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Fármacos Anti-VIH
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
2015
Tipo del documento:
Article
País de afiliación:
China