摘要
Enzyme-instructed self-assembly （EISA） offers a facile approach to explore the supramolecular assemblies of small molecules in cellular milieu for a variety of biomedical applications. One of the commonly used enzymes is phosphatase, but the study of the substrates of phosphatases mainly focuses on the phos- photyrosine containing peptides. In this work, we examine the EISA of phosphoserine containing small peptides for the first time by designing and synthesizing a series of precursors containing only phosphoserine or both phos- phoserine and phosphotyrosine. Conjugating a phospho- serine to the C-terminal of a well-established self- assembling peptide backbone, （naphthalene-2-1y）-acetyl- diphenylalanine （NapFF）, affords a novel hydrogelation precursor for EISA. The incorporation ofphosphotyrosine, another substrate of phosphatase, into the resulting precursor, provides one more enzymatic trigger on a single molecule, and meanwhile increases the precursors＇ propensity to aggregate after being fully dephosphorylated. Exchanging the positions of phosphorylated serine and tyrosine in the peptide backbone provides insights on how the specific molecular structures influence self-assembling behaviors of small peptides and the subsequent cellular responses. Moreover, the utilization of D-amino acids largely enhances the biostability of the peptides, thus providing a unique soft material for potential biomedical applications.
Enzyme-instructed self-assembly （EISA） offers a facile approach to explore the supramolecular assemblies of small molecules in cellular milieu for a variety of biomedical applications. One of the commonly used enzymes is phosphatase, but the study of the substrates of phosphatases mainly focuses on the phos- photyrosine containing peptides. In this work, we examine the EISA of phosphoserine containing small peptides for the first time by designing and synthesizing a series of precursors containing only phosphoserine or both phos- phoserine and phosphotyrosine. Conjugating a phospho- serine to the C-terminal of a well-established self- assembling peptide backbone, （naphthalene-2-1y）-acetyl- diphenylalanine （NapFF）, affords a novel hydrogelation precursor for EISA. The incorporation ofphosphotyrosine, another substrate of phosphatase, into the resulting precursor, provides one more enzymatic trigger on a single molecule, and meanwhile increases the precursors＇ propensity to aggregate after being fully dephosphorylated. Exchanging the positions of phosphorylated serine and tyrosine in the peptide backbone provides insights on how the specific molecular structures influence self-assembling behaviors of small peptides and the subsequent cellular responses. Moreover, the utilization of D-amino acids largely enhances the biostability of the peptides, thus providing a unique soft material for potential biomedical applications.
