The present invention relates to a water-soluble polymeric reagent of the structure: wherein: POLY is a water soluble polymer Y has the formula -(CR R )n-, where n is 3 to 8, and each of R1 and R2 is independently selected from hydrogen, lower alkyl, lower alkenyl, and a non-interfering substituents, where two groups R1 and R2 on different carbon atoms may be linked to form a cycloalkyl-, or aryl group S is a sulfur atom attached to an sp3 hybridized carbon of Y S-W is a thiol, protected thiol, or thiol-reactive thiol derivative x = 1 - 25 and if POLY is a linear polyethylene glycol, x=l, and Y is a linear alkyl chain then 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.