| 摘要 |
2068651 9205188 PCTABS00011 The present invention relates to processes for producing multimeric glycoproteins involving the steps of: 1) oxidizing a solution including glycosylated polypeptides to produce aldehyde-functional glycoproteins; 2) reacting the aldehyde-functional glycoproteins with an aminothiol compound to produce thiol-functional glycoproteins; and 3) chemically coupling two or more thiol-functional glycoproteins through a direct disulfide bond or through a homobifunctional cross-linking agent. This invention also relates to multimeric glycoproteins having the general formula: P1G1-(N1)-R1-S-X-S-R2-(N2)-G2P2, wherein: P1 and P2 represent the same or different polypeptides; G1 and G2 represent the same or different glycosyl moieties on the polypeptides P1 and P2, respectively; (N1) and (N2) represent, independently, a linkage between G1 and R1 or G2 and R2, respectively, through a secondary or tertiary amine nitrogen atom, i.e., (N1) and (N2) may either represent an imino (-NH-) or anaza (=N- or -N=) linkage between the glycosyl moieties (G1, G2) and the R1 and R2 moieties; R1 and R2 represent the same or different organic radicals of 1-16 carbon atoms or polypeptides of up to 20 amino acids; S is sulfur; and X is a direct bond or is a divalent organic radical of from 1-16 carbon atoms. This invention also relates to multimeric forms of soluble CD4, soluble LFA3 and soluble VCAM-1b proteins.
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