title: Trp-Arg-Xaa tripeptides act as uncompetitive-type inhibitors of human dipeptidyl peptidase IV.
abstract: Human dipeptidyl peptidase IV (hDPPIV, alternative name: CD26) inhibitors provide an effective strategy for the treatment of type 2 diabetes. Recently, our research group discovered a non substrate-mimic inhibitory dipeptide, Trp-Arg, by the systematic analysis of a dipeptide library. In the present study, a tripeptide library Trp-Arg-Xaa (where Xaa represents any amino acid) was analyzed to investigate the interactions of peptidergic inhibitors with hDPPIV. Trp-Arg-Glu showed the highest inhibitory effect toward hDPPIV (Ki=130 μM). All of the tested 19 Trp-Arg-Xaa tripeptides showed unique uncompetitive-type inhibition. The inhibition mechanism of Trp-Arg-Xaa is discussed based on the crystal structure of hDPPIV. The information obtained by this study suggests a novel concept for developing hDPPIV inhibitory peptides and drugs.
authors: Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Yada 52-1, Suruga-ku, Shizuoka 422-8526, Japan.
authors: Vu Thi Tuyet
authors: VT
authors: Lan
authors: Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Yada 52-1, Suruga-ku, Shizuoka 422-8526, Japan. Electronic address: sukeito@u-shizuoka-ken.ac.jp.
authors: Keisuke
authors: K
authors: Ito
authors: Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Yada 52-1, Suruga-ku, Shizuoka 422-8526, Japan.
authors: Sohei
authors: S
authors: Ito
authors: Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Yada 52-1, Suruga-ku, Shizuoka 422-8526, Japan.
authors: Yasuaki
authors: Y
authors: Kawarasaki
mesh_terms: D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D019151:Peptide Library; D010455:Peptides; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4