Stabilized polymeric thiol reagents
AssigneeNektar Therapeutics
InventorsAntoni Kozlowski, Samuel McManus
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Abstract
Disclosed are water soluble polymeric conjugates comprising the structure POLY-[Y—S—S-A]x, where POLY is a water soluble polymer; Y is a hydrocarbon-based spacer group, x is 1 to 25, S—S is a disulfide group attached to an sp3 hybridized carbon of Y; and A is a covalently linked residue of a pharmacologically active molecule. Preferably, the water soluble polymer is a PEG polymer. Also disclosed are polymeric reagents useful to prepare such conjugates, and methods of their formation and use.
Claims16
A polymer conjugate comprising the structure:
- POLY-[Y—S—S-A]x
- wherein:
- POLY is a water soluble polymer;
- Y has the formula —(CR1R2)n—, where n is 4 to 8, each of R1 and R2 is independently selected from hydrogen, lower alkyl, lower alkenyl, and a non-interfering substituent, where two groups R1 and R2 on different carbon atoms may be linked to form a cycloalkyl or aryl group;
- S—S is a disulfide group attached to an sp3 hybridized carbon of Y;
- and
- A is a covalently linked residue of a pharmacologically active molecule;
- and
- x is 1-25, and
- if POLY is a linear polyethylene glycol, x=1, and Y is a linear alkyl chain, the POLY has a molecular weight of at least 500,
- wherein when S—W is the disulfide linkage ortho-pyridyl disulfide and POLY is a linear polyethylene glycol, at least one R1 on a carbon adjacent to said disulfide linkage is lower alkyl.
The conjugate of claim 9, wherein each of R1 and R2 is independently selected from hydrogen and methyl.
Dependencies are inferred from the claim text.