title: Nonpeptide-Based Small-Molecule Probe for Fluorogenic and Chromogenic Detection of Chymotrypsin.
abstract: We report herein a nonpeptide-based small-molecule probe for fluorogenic and chromogenic detection of chymotrypsin, as well as the primary application for this probe. This probe was rationally designed by mimicking the peptide substrate and optimized by adjusting the recognition group. The refined probe 2 exhibits good specificity toward chymotrypsin, producing about 25-fold higher enhancement in both the fluorescence intensity and absorbance upon the catalysis by chymotrypsin. Compared with the most widely used peptide substrate (AMC-FPAA-Suc) of chymotrypsin, probe 2 shows about 5-fold higher binding affinity and comparable catalytical efficiency against chymotrypsin. Furthermore, it was successfully applied for the inhibitor characterization. To the best of our knowledge, probe 2 is the first nonpeptide-based small-molecule probe for chymotrypsin, with the advantages of simple structure and high sensitivity compared to the widely used peptide-based substrates. This small-molecule probe is expected to be a useful molecular tool for drug discovery and chymotrypsin-related disease diagnosis.
authors.affiliation: Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University , Wuhan 430079, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wu
authors.affiliation: Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University , Wuhan 430079, P.R. China.
authors.forename: Shu-Hou
authors.initials: SH
authors.lastname: Yang
authors.affiliation: Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University , Wuhan 430079, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Xiong
authors.affiliation: Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University , Wuhan 430079, P.R. China.
authors.forename: Jia-Qian
authors.initials: JQ
authors.lastname: Yang
authors.affiliation: Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University , Wuhan 430079, P.R. China.
authors.forename: Jun
authors.identifier: 0000-0002-2097-5054
authors.initials: J
authors.lastname: Guo
authors.affiliation: Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University , Wuhan 430079, P.R. China.
authors.forename: Wen-Chao
authors.identifier: 0000-0002-6722-0441
authors.initials: WC
authors.lastname: Yang
authors.affiliation: Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University , Wuhan 430079, P.R. China.|Collaborative Innovation Center of Chemical Science and Engineering, Tianjin 30071, P.R. China.
authors.forename: Guang-Fu
authors.identifier: 0000-0003-4384-2593
authors.initials: GF
authors.lastname: Yang
mesh_terms: D002918:Chymotrypsin / Q000032:analysis*; D005456:Fluorescent Dyes / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D054852:Small Molecule Libraries / Q000737:chemistry*
chemical_list: D005456:Fluorescent Dyes; D010455:Peptides; D054852:Small Molecule Libraries; D002918:Chymotrypsin