Multi-armed, monofunctional, and hydrolytically stable derivatives of poly(ethylene glycol) and related polymers for modification of surfaces and molecules
First Claim
1. A method for preparing a branched, monofunctional, water-soluble polymer, the method comprising:
- (i) reacting a monomethoxypoly(ethylene glycol)polymer comprising a single reactive moiety, W, and having the structure mPEG-W, where W is the single reactive moiety, with a linker molecule comprising from 1 to 10 carbon atoms and having the structure X—
C(Y)(R)—
Z,where X and Y each independently comprise reactive groups that can react with W to form hydrolytically stable linkage fragments P and Q, respectively,Z is a moiety that (a) comprises a single ionizable reactive site that is capable of reacting with ion exchange chromatography media, and (b) is not reactive with either X or Y, andR is H, methyl or another alkyl group,under conditions effective to provide an impure branched monofunctional, water-soluble polymer having the structure;
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Abstract
Multi-armed, monofunctional, and hydrolytically stable polymers are described having the structure
wherein Z is a moiety that can be activated for attachment to biologically active molecules such as proteins and wherein P and Q represent linkage fragments that join polymer arms polya and polyb, respectively, to central carbon atom, C, by hydrolytically stable linkages in the absence of aromatic rings in the linkage fragments. R typically is hydrogen or methyl, but can be a linkage fragment that includes another polymer arm. A specific example is an mPEG disubstituted lysine having the structure
where mPEGa and mPEGb have the structure CH3O—(CH2CH2O)nCH2CH2— where n may be the same or different for polya- and polyb- and can be from 1 to about 1,150 to provide molecular weights of from about 100 to 100,000.
28 Citations
20 Claims
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1. A method for preparing a branched, monofunctional, water-soluble polymer, the method comprising:
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(i) reacting a monomethoxypoly(ethylene glycol)polymer comprising a single reactive moiety, W, and having the structure mPEG-W, where W is the single reactive moiety, with a linker molecule comprising from 1 to 10 carbon atoms and having the structure X—
C(Y)(R)—
Z,where X and Y each independently comprise reactive groups that can react with W to form hydrolytically stable linkage fragments P and Q, respectively, Z is a moiety that (a) comprises a single ionizable reactive site that is capable of reacting with ion exchange chromatography media, and (b) is not reactive with either X or Y, and R is H, methyl or another alkyl group, under conditions effective to provide an impure branched monofunctional, water-soluble polymer having the structure; - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20)
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Specification