Total chemical synthesis and high-resolution crystal structure of the potent anti-HIV protein AOP-RANTES.
Chem Biol
; 6(1): 43-51, 1999 Jan.
Article
em En
| MEDLINE
| ID: mdl-9889151
ABSTRACT
BACKGROUND:
RANTES is a CC-type chemokine protein that acts as a chemoattractant for several kinds of leukocytes, playing an important pro-inflammatory role. Entry of human immunodeficiency virus-1 (HIV-1) into cells depends on the chemokine receptor CCR5. RANTES binds CCR5 and inhibits HIV-1 entry into peripheral blood cells. Interaction with chemokine receptors involves a distinct set of residues at the amino terminus of RANTES. This finding was utilized in the development of a chemically modified aminooxypentane derivative of RANTES, AOP-RANTES, that was originally produced from the recombinant protein using semisynthetic methods.RESULTS:
AOP-RANTES has been produced by a novel total chemical synthesis that provides efficient, direct access to large amounts of this anti-HIV protein analog. The crystal structure of chemically synthesized AOP-RANTES has been solved and refined at 1.6 A resolution. The protein is a dimer, with the amino-terminal pentane oxime moiety clearly defined.CONCLUSIONS:
Total chemical synthesis of AOP-RANTES provides a convenient method of producing the multi-milligram quantities of this protein needed to investigate the molecular basis of receptor binding and antiviral activity. This work provides the first truly high-resolution structure of a RANTES protein, although the structure of RANTES was known from previous nuclear magnetic resonance (NMR) determinations.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quimiocina CCL5
/
Fármacos Anti-HIV
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Chem Biol
Assunto da revista:
BIOLOGIA
/
BIOQUIMICA
/
QUIMICA
Ano de publicação:
1999
Tipo de documento:
Article
País de afiliação:
Estados Unidos