A multi-functional peptide as an HIV-1 entry inhibitor based on self-concentration, recognition, and covalent attachment.
Org Biomol Chem
; 10(32): 6512-20, 2012 Aug 28.
Article
em En
| MEDLINE
| ID: mdl-22760295
ABSTRACT
HIV entry is mediated by the envelope glycoproteins gp120 and gp41. The gp41 subunit contains several functional domains the N-terminal heptad repeat (NHR) domains fold a triple stranded coiled-coil forming a meta-stable prefusion intermediate. The C-terminal heptad repeat (CHR) subsequently folds onto the hydrophobic grooves of the NHR coiled-coil to form a stable 6-helix bundle, which juxtaposes the viral and cellular membranes for fusion. A conserved salt bridge between Lys(574) in NHR and Asp(632) in CHR plays an essential role in the formation of the six-helix bundle. A multi-functional peptide inhibitor for anti-HIV derived from the CHR of gp41 has been designed. It bears a cholesterol group (Chol) at the C-terminal through which the inhibitor can anchor in the cell membrane, and carries an isothiocyanate (NCS) group at the side chain of Asp(632) through which the inhibitor can bind to target covalently at Lys(574) in NHR. The dual functionalized peptide (NCS-C34-Chol) shows high antiviral activity in vitro and in vivo. The inhibitor reacts specifically and rapidly to NHR from gp41. In addition, it exhibits better stability under the digestion of the Proteinase K than C34 and T20.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
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Desenho de Fármacos
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Proteína gp41 do Envelope de HIV
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Fármacos Anti-HIV
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Inibidores da Fusão de HIV
Limite:
Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article