Poly(dehydroalanine): Synthesis, Properties, and Functional Diversification of a Fluorescent Polypeptide

Via the design of a new, soluble poly(S-alkyl-L-cysteine) precursor, a route was developed for the successful preparation of long-chain poly(dehydroalanine), ADH, as well as the incorporation of dehydroalanine residues and A(DH) segments into copolypeptides. Based on experimental and computational data, A(DH) was found to adopt a previously unobserved "hybrid coil" structure, which combines the elements of 2(5)-helical and 3(10)-helical conformations. Analysis of the spectroscopic properties of A(DH) revealed that it possesses a strong inherent blue fluorescence, which may be amenable for use in imaging applications. A(DH) also contains reactive electrophilic groups that allowed its efficient modification to functionalized polypeptides after reactions under mild conditions with thiol and amine nucleophiles. The combined structural, spectroscopic, and reactivity properties of A(DH) make it a unique reactive and fluorescent polypeptide component for utilization in self-assembled biomaterials.