Chemical conjugates for targeted degradation under reducing conditions

摘要

The present invention is related to compositions which can undergo targeted degradation under certain physiological reducing conditions. The compositions may, for example, be hydrogels in which maleimide-functionalized low molecular weight heparin is cross-linked with various thiol-functionalized polyethylene glycol multi-arm star polymers. Both the gelation and degradation of the hydrogels can be modified by careful selection of the thiol. For example, hydrogels prepared from aryl thiol-maleimide adducts can undergo a retro Michael addition-type reaction, leading to degradation of the composition and release of the bioactive molecule.

主权项

1. A composition comprising a bioactive molecule and a second component, wherein the bioactive molecule and the second component are linked by one or more linking units comprising a thioether structural unit having the structural formula -A-S—R— where A is an aryl moiety or a heteroaromatic ring moiety and R is a succinimide moiety and obtained by Michael-type addition of a thiol to a maleimide group and wherein the thiol has a pKa of less than 8, and wherein the composition is capable of undergoing a retro Michael-type addition reaction under physiological conditions.