PEGylation extends circulation half-life while preserving in vitro and in vivo activity of tissue inhibitor of metalloproteinases-1 (TIMP-1).

ABSTRACT: Excess proteolytic activity of matrix metalloproteinases (MMPs) contributes to the development of arthritis, cardiovascular diseases and cancer progression, implicating these enzymes as therapeutic targets. While many small molecule inhibitors of MMPs have been developed, clinical uses have been limited, in part by toxicity and off-target effects. Development of the endogenous tissue inhibitors of metalloproteinases (TIMPs) as recombinant biopharmaceuticals represents an alternative therapeutic approach; however, the short plasma half-life of recombinant TIMPs has restricted their potential in this arena. To overcome this limitation, we have modified recombinant human TIMP-1 (rhTIMP-1) by PEGylation on lysine residues. We analyzed a mixture of mono- and di-PEGylated rhTIMP-1 species modifi

SUBMITTER: Batra J 

PROVIDER: S-EPMC3502186 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature