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Titolo:
A MODEL ALLOWING THE DESIGN OF MODIFIED NUCLEOSIDES AS HIV-RT INHIBITORS
Autore:
PEPE G; MEYER M; FAURY P; GRACIET JC; CHERMANN JC; KRAUS JL;
Indirizzi:
LAB UNIV AIX MARSEILLE 2,CRMC2,CNRS,CAMPUS UNIV LUMINY,CASE 913 F-13288 MARSEILLE 9 FRANCE LAB UNIV AIX MARSEILLE 3,CRMC2,CNRS F-13288 MARSEILLE 9 FRANCE INSERM U322,UNITE RETROVIRUS & MALAD ASSOCIEES F-13273 MARSEILLE 9 FRANCE FAC SCI LUMINY,LAB CHIM BIOMOL F-13288 MARSEILLE 9 FRANCE
Titolo Testata:
European journal of medicinal chemistry
fascicolo: 10, volume: 31, anno: 1996,
pagine: 775 - 786
SICI:
0223-5234(1996)31:10<775:AMATDO>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
IMMUNODEFICIENCY-VIRUS-INFECTION; REVERSE-TRANSCRIPTASE; CRYSTAL-STRUCTURE; ANGSTROM RESOLUTION; COMPUTER-PROGRAM; NUCLEIC-ACIDS; SIMILARITY; ANALOGS; 3'-AZIDO-3'-DEOXYTHYMIDINE; INDUCTION;
Keywords:
HIV RT; INHIBITOR; NUCLEOSIDE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
47
Recensione:
Indirizzi per estratti:
Citazione:
G. Pepe et al., "A MODEL ALLOWING THE DESIGN OF MODIFIED NUCLEOSIDES AS HIV-RT INHIBITORS", European journal of medicinal chemistry, 31(10), 1996, pp. 775-786

Abstract

A chemical, structural, molecular electrostatic potential (MEP) analysis of modified nucleosides allows the understanding of how nucleosides interact with different receptors. The interaction with kinases is sensitive to base modifications, while the interaction with the reversetranscriptase receptor HIV active site is more affected by ribose modifications, The model herein indicates a geometrical lower limit in the width of the modified sugar that corresponds to the 3' erythro position. This characteristic allows one to predict a potential activity ofthe 3' substituted compounds. The 4'-hydroxymethyl group position with respect to the nucleic base is also important for antiviral activity. The model gives the geometric parameters of this position (related to kinetic effects) that corresponds to an increase in the activation energy required to fit the active site of the kinases and the RT. Our model is compatible with the 3D structure of the HIV RT active site. Itallows the design of potent new active compounds where the sugar can be substituted by any group answering to the defined parameters.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 11:54:31