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Titolo:
MODIFICATION OF CD4 IMMUNOADHESIN WITH MONOMETHOXYPOLY(ETHYLENE GLYCOL) ALDEHYDE VIA REDUCTIVE ALKYLATION
Autore:
CHAMOW SM; KOGAN TP; VENUTI M; GADEK T; HARRIS RJ; PEERS DH; MORDENTI J; SHAK S; ASHKENAZI A;
Indirizzi:
GENENTECH INC,DEPT PROC SCI,460 POINT SAN BRUNO BLVD S SAN FRANCISCO CA 94080 GENENTECH INC,DEPT BIOORGAN CHEM S SAN FRANCISCO CA 94080 GENENTECH INC,DEPT BIOORGAN CHEM S SAN FRANCISCO CA 94080 GENENTECH INC,DEPT MED & ANALYT CHEM S SAN FRANCISCO CA 94080 GENENTECH INC,DEPT GENE THERAPY & PULM RES S SAN FRANCISCO CA 94080 GENENTECH INC,DEPT EXPTL THERAPEUT & MOLEC BIOL S SAN FRANCISCO CA 94080
Titolo Testata:
Bioconjugate chemistry
fascicolo: 2, volume: 5, anno: 1994,
pagine: 133 - 140
SICI:
1043-1802(1994)5:2<133:MOCIWM>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN-IMMUNODEFICIENCY-VIRUS; RECOMBINANT SOLUBLE CD4; AIDS-RELATED COMPLEX; POLYETHYLENE-GLYCOL; POLY(ETHYLENE GLYCOL); COVALENT ATTACHMENT; CIRCULATING LIFE; ENVELOPE GLYCOPROTEIN; BIOLOGICAL PROPERTIES; CHEMICAL MODIFICATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
53
Recensione:
Indirizzi per estratti:
Citazione:
S.M. Chamow et al., "MODIFICATION OF CD4 IMMUNOADHESIN WITH MONOMETHOXYPOLY(ETHYLENE GLYCOL) ALDEHYDE VIA REDUCTIVE ALKYLATION", Bioconjugate chemistry, 5(2), 1994, pp. 133-140

Abstract

CD4 immunoadhesin (CD4-IgG) is a chimeric glycoprotein molecule comprised of the gp120-binding portion of human CD4 fused to the hinge and Fc portions of human IgG. As a candidate for human therapeutic use, CD4-IgG represents an important advance over soluble CD4, insofar as thesystemic clearance in humans of CD4-IgG is significantly slower. In an effort to prolong its in vivo residence time even further, we have modified CD4-IgG chemically by attaching monomethoxypoly(ethylene glycol) (MePEG) moieties to lysine residues via reductive alkylation. We synthesized MePEG aldehyde and investigated reaction conditions for adding a range of MePEG moieties per protein molecule. At neutral pH in the presence of sodium cyanoborohydride, the reaction was sufficiently slow to allow for significant control over the extent of MePEGylation. Addition of 7.7 or 14.4 MePEG moieties to CD4-IgG resulted in an approximately 4- or 5-fold increase, respectively, in the persistence of the protein in rats, as compared with unmodified CD4-IgG. These results suggest that the therapeutic utility of a human receptor IgG chimera can be improved by MePEGylation technology, provided that the modified immunoadhesin retains its biological activity in vivo. Such modification can lead to a significant additional increase in the in vivo residence time of the protein.

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Documento generato il 05/12/20 alle ore 20:11:27