title: An Orally Active Bradykinin B1Receptor Antagonist Engineered as a Bifunctional Chimera of Sunflower Trypsin Inhibitor.
abstract: An orally active and metabolically stable peptide TIBA was successfully engineered as a chimera by fusing an analgesic bradykinin receptor antagonist peptide and the trypsin inhibitory loop of sunflower trypsin inhibitor-1. As a fusion cyclic peptide, the metabolically labile analgesic peptide is protected from degradation by exopeptidases as well as the endopeptidases, and its serum half-life extended from <5 min to >6 h as a chimera. Moreover, the chimera TIBA was also found to be orally active in an animal pain model using a hot plate assay.
authors.affiliation: School of Biological Sciences, Nanyang Technological University , 60 Nanyang Drive, 637551, Singapore.
authors.forename: Yibo
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Biofunctional Synthetic Chemistry Laboratory , RIKEN 2-1 Hirosawa, Wako-shi, Saitama, 351-0198, Japan.
authors.forename: Misako
authors.initials: M
authors.lastname: Taichi
authors.affiliation: School of Chemical and Biomedical Engineering, Nanyang Technological University , 62 Nanyang Drive, 637459, Singapore.
authors.forename: Na
authors.initials: N
authors.lastname: Wei
authors.affiliation: School of Pharmacy, Jiangsu University , 301 Xuefu Road, Zhenjiang, Jiangsu 212013, P. R. China.
authors.forename: Huan
authors.initials: H
authors.lastname: Yang
authors.affiliation: Faculty of Health Sciences, University of Macau , Taipa, Macau, P. R. China.
authors.forename: Kathy Qian
authors.initials: KQ
authors.lastname: Luo
authors.affiliation: School of Biological Sciences, Nanyang Technological University , 60 Nanyang Drive, 637551, Singapore.
authors.forename: James P
authors.identifier: 0000-0003-4433-198X
authors.initials: JP
authors.lastname: Tam
mesh_terms: D000284:Administration, Oral; D065169:Bradykinin B1 Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D056148:Chromatography, Reverse-Phase; D006368:Helianthus / Q000737:chemistry*; D014361:Trypsin Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D065169:Bradykinin B1 Receptor Antagonists; D014361:Trypsin Inhibitors