Metal-bound claMP Tag inhibits proteolytic cleavage.

Biologics can be an improvement to small molecule drugs, providing high specificity for an identified target, lowering toxicity and limiting side effects. To achieve effective delivery, the biologic must have sufficient time to reach the target tissue. A prolonged half-life in the circulating environment is desired, but often serum stability is limited by proteases. Proteolysis in the serum causes degradation and inactivation as the biologic is fragmented and more rapidly cleared from the body. To improve the circulating half-life, large, hydrophilic polymers may be conjugated or stable fusion tags may be engineered to increase the effective size of the peptide and to hinder degradation by proteases. Improved resistance to proteases is essential for effective delivery. Here, a proof of concept study is presented using a metal-binding tripeptide tag known as the claMP Tag to create an inline conjugate and the ability of the tag to inhibit proteolysis was examined.