Thiol-selective water-soluble polymer derivatives
View Patent ↗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, as well as methods for preparing the water-soluble, polymer derivatives having a thiol-selective terminus.
1. A polymer having the following structure:
POLY-L 0,1 -X—Y—S—S—Y—X-L 0,1 -POLY
wherein:
POLY is an end-capped polyalkylene oxide;
L is an optional linker;
X is selected from the group consisting of amide, carbamate, carbonate ester, ether and thioester;
Y is selected from the group consisting of alkylene, substituted alkylene, cycloalkylene, substituted cycloalkylene, aryl, and substituted aryl, comprising from about 2 to about 10 carbon atoms; and
S is a sulfur atom.
2. The polymer of claim 1 , wherein L 1 is a linker selected from the group consisting of C 1 -C 10 alkyl and C 1 -C 10 substituted alkyl.
3. The polymer of claim 1 , wherein L 1 is a linker selected from the group consisting of (CH 2 ) 1, 2, 3, 4 and 5 .
4. The polymer of claim 1 , wherein L is —CH 2 —.
5. The polymer of claim 1 , wherein POLY is a polyethylene glycol having the structure H 3 CO—(CH 2 CH 2 O) n CH 2 CH 2 — wherein n ranges from 10 to about 4,000.
6. The polymer of claim 1 , wherein L is absent (L 0 ).