Development of Nonfouling Zwitterionic Copolymerized Peptides Based on Glutamic Acid and Lysine Dimers for Adjustable Enzymatic Degradation

Nonspecific protein adsorption-resistant materials, the so-called nonfouling materials, are crucial biomaterials in biomedical applications. Up-to-date, little attention was paid to the biodegradability of these materials. In this work, nonfouling zwitterionic copolymerized peptides composed of the N-l-glumatyl-l-lysine dimer (EK) and δ-l-lysinyl-l-glutamic acid dimer (E-K, glutamic acid with the lysine side chain) at various ratios were synthesized to investigate the enzymatic degradation rate. Two types of proteases (trypsin and alkaline protease), which represent a site-specific and less site-specific cleavage protease, respectively, were used to demonstrate the adjustable degradability by tracking the molecular weight (Mw) at different digestion times. Results showed that higher compositions of the E-K dimer lead to slower degradation rates by both proteases and larger fragments after 120 min digestion. With the composition of the E-K dimer over 50%, the degradation of copolymerized peptides by both proteases becomes very slow. This indicated that the bulky lysinyl side chain on E-K can alter the enzymolysis process for adjusting the enzymatic degradability of the newly synthesized zwitterionic copolymerized peptides, which could be promising candidates for biomedical applications in vivo.