Methods for preparing functionalized polymers from polymer alcohols
The present invention provides, among other things, compounds that include a water-soluble and non-peptidic polymer as well as a maleimidyl group. The compounds are useful as, among other things, polymeric reagents.
1. A method for forming a purified composition of monosubstituted methoxy poly(ethylene glycol) (mPEG) comprising a single functional group, Y, from a mixture of mPEG and PEG diol, comprising the steps of:
(a) reacting a mixture comprising mPEG and PEG diol, in one or more reaction steps, with one or more functionalizing reagents to effect the introduction of an ionizable functional group, Y, to form a composition comprising (i) monosubstituted mPEG comprising a single Y group, and (ii) disubstituted PEG, under conditions effective to convert substantially all hydroxyl groups in the mixture to Y groups; and
(b) purifying the composition from step (a) to provide the purified composition of monosubstituted mPEG comprising a single Y group substantially free from disubstituted PEG.
2. The method of claim 1 , wherein the PEG diol concentration in the mixture comprising mPEG and PEG diol in step (a) is from about 0.5% to about 40%.
3. The method of claim 1 , wherein the purifying step comprises passing the composition from step (a) through an ion exchange column to provide an eluate, wherein said passing step is carried out under conditions effective to adsorb substantially all of said disubstituted PEG onto the column.
4. The method of claim 3 , wherein monosubstituted mPEG comprising a single Y group is recovered from the eluate.
5. The method of claim 1 , wherein Y is a carboxylic acid.
6. The method of claim 1 , wherein Y is an amine.
7. The method of claim 1 , further comprising the step of converting the Y group of the monosubstituted mPEG comprising a single Y group to a hydroxyl group or a hydroxyl-containing group.