AbstractBowman-Birk type proteinase inhibitors (BBIs) is a typical family of canonical serine protease inhibitors specially derived from plants which can inhibit serine proteases, like trypsin and chymotrypsin. BBIs have various functions, such as for suppress cancer cell proliferation and decrease inflammatory responses, etc. Recent developments in the field of BBIs have led to a renewed interest in amphibian skin-derived BBIs which have a much shorter chain and remarkable inhibitory effect.
In this study, a bioactive peptide, QUB-1904, was discovered from skin secretion of Pelophylax esculentus by shotgun cloning of a novel biosynthetic precursor encoded cDNA smoothly. Through the bioinformatic analysis, the amino-acid sequences of mature peptide was determined as SAPRGCWTKSYPPKPCK and ended with a C terminal amide. After chemically synthesis, RP-HPLC and MALDI were subjected to the detection and purification of QUB-1904. The lyophilised pure peptide replicates were subjected to different assays and examinations were operated to evaluate different aspects of bioactivity of QUB-1904. The results appeal that QUB-1904 is a potential trypsin inhibitor, with a Ki value of 0.2504 µM. Whilst, this peptide possesses no antimicrobial activity on S. aureus, E. coli and C. albicans neither anti-proliferation activity on the human cancer cells, H-157, PC-3, U251MG and MCF-7. Although QUB-1904 is not a multifunctional bioactive peptide discovered from amphibian skin secretion, it could be used as a template for development of new trypsin inhibitory drugs.
|Date of Award||07 Aug 2018|
|Supervisor||Tianbao Chen (Supervisor), Lei Wang (Supervisor), Mei Zhou (Supervisor), Christopher Shaw (Supervisor) & Xinping Xi (Supervisor)|