An Orally Active Bradykinin B1 Receptor Antagonist Engineered as a Bifunctional Chimera of Sunflower Trypsin Inhibitor

  • J Med Chem. 2017 Jan 12;60(1):504-510. doi: 10.1021/acs.jmedchem.6b01011.
Yibo Qiu  1 ,  Misako Taichi  2 ,  Na Wei  3 ,  Huan Yang  4 ,  Kathy Qian Luo  5 ,  James P Tam  1
Affiliations
  • 1. School of Biological Sciences, Nanyang Technological University , 60 Nanyang Drive, 637551, Singapore.
  • 2. Biofunctional Synthetic Chemistry Laboratory , RIKEN 2-1 Hirosawa, Wako-shi, Saitama, 351-0198, Japan.
  • 3. School of Chemical and Biomedical Engineering, Nanyang Technological University , 62 Nanyang Drive, 637459, Singapore.
  • 4. School of Pharmacy, Jiangsu University , 301 Xuefu Road, Zhenjiang, Jiangsu 212013, P. R. China.
  • 5. Faculty of Health Sciences, University of Macau , Taipa, Macau, P. R. China.
PMID: 27977181 DOI: 10.1021/acs.jmedchem.6b01011
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.