期刊
ACS COMBINATORIAL SCIENCE
卷 13, 期 3, 页码 310-320出版社
AMER CHEMICAL SOC
DOI: 10.1021/co200006z
关键词
combinatorial libraries; peptide dendrimer; hydrolysis; isobutyryl fluorescein; enzyme models
资金
- University of Berne
- Swiss National Science Foundation
- Marie Curie Training Network IBAAC
Two 6750-membered one-bead-one-compound peptide dendrimer combinatorial libraries L (X-4)(8)(LysX(3))(4)(LysX(2))(2)LysX(1) (X1-4 = 14 different amino acids or deletion, Lys = branching lysine residue) and AcL (with N-terminal acetylation) were prepared by split-and-mix solid phase peptide synthesis. Screening toward fluorogenic substrates for esterase and aldolase activities using the in silica off-bead assay (N. Maillard et al., J. Comb. Chem. 2009, 11, 667-675) and bead decoding by amino acid analysis revealed histidine containing sequences active against fluorescein diacetate. Isobutyryl fluorescein, a related hydrophobic fluorogenic substrate, was preferentially hydrolyzed by dendrimers from library AcL containing hydrophobic residues such as ACH3 (AcHis)(8)(LysLeu)(4)(LysVal)(2)LysLysOH, compared to simple oligohistidine peptides as reference catalysts. Polycationic dendrimers from library L with multiple free N-termini such as H8 (His)(8)(Lys beta Ala)(4)(LysThr)(2)LysaProNH(2) (aPro = (2S,4S)-4-aminoproline) showed stronger reactivity toward 8-acetoxypyrene-1,3,6-trisulfonate with partial acylation of N-termini. These experiments highlight the role of noncatalytic amino acids to determine substrate selectivity in peptide dendrimer esterase models.
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