Thiol-selective water-soluble polymer derivatives

摘要

The present invention provides water-soluble, polymer derivatives having a thiol-selective terminus suitable for selective coupling to thiol groups, such as those contained in the cysteine residues of proteins.

主权项

1. A method for preparing a thiol-selective derivative of a water-soluble polymer comprising the steps of:
(i) providing an electrophilically-activated polymer, POLY-L0,1-E, wherein:
POLY is a water-soluble polymer segment,L is an optional linker,E is an electrophile, and (ii) reacting the POLY-L0,1-E with a symmetrical disulfide reagent, (NU-Y-S-)2, wherein:
NU is a nucleophile, andY is alkylene, substituted alkylene, cycloalkylene, substituted cycloalkylene, aryl, or substituted aryl, comprising from about 2 to about 10 carbon atoms, under conditions effective to promote reaction between E and NU to thereby form POLY-L0,1-X-Y-S-S-Y-X-L0,1-POLY, wherein X is a group resulting from the reaction between E and NU.