Synthesis and Characterization of Highly Thiolated Silk Fibroin

Abstract Covalent attachment of thiols to the tyrosine residues of silk fibroin is accomplished with a high degree of functionalization through the reaction of a pyridyldithiol‐containing N‐hydroxysuccinimidal‐ester and an amino‐tyrosine silk intermediate. The extent of thiol modification is characterized by 1 H NMR and UV–vis spectroscopy. Further modification of the thiol groups is probed by reacting with an iodoacetamide‐containing small molecule resulting in a novel fluorescent silk derivative. Last, the ability of the thiolated silk to form hydrogels in situ is investigated.