home
***
CD-ROM
|
disk
|
FTP
|
other
***
search
/
Shareware Overload Trio 2
/
Shareware Overload Trio Volume 2 (Chestnut CD-ROM).ISO
/
dir26
/
med9408c.zip
/
M9480622.TXT
< prev
next >
Wrap
Text File
|
1994-08-20
|
3KB
|
41 lines
Document 0622
DOCN M9480622
TI Modification of CD4 immunoadhesin with monomethoxypoly(ethylene glycol)
aldehyde via reductive alkylation.
DT 9410
AU Chamow SM; Kogan TP; Venuti M; Gadek T; Harris RJ; Peers DH; Mordenti J;
Shak S; Ashkenazi A; Department of Process Science, Genentech, Inc.,
South San; Francisco, California 94080.
SO Bioconjug Chem. 1994 Mar-Apr;5(2):133-40. Unique Identifier : AIDSLINE
MED/94304966
AB 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 the
systemic 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.
DE Alkylation Animal CD4 Immunoadhesins/*CHEMISTRY Electrophoresis,
Polyacrylamide Gel Human HIV Envelope Protein gp120/METABOLISM
IgG/CHEMISTRY Male Nuclear Magnetic Resonance Oxidation-Reduction
Peptide Mapping Polyethylene Glycols/*CHEMISTRY/CHEMICAL SYNTHESIS
Rats Rats, Sprague-Dawley Recombinant Proteins/CHEMISTRY Sequence
Analysis JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).