An exhaustive search of new bioactive peptides based on prediction by bioinformatics using human genome structures

点击翻译按钮获取中文摘要

1) Based on biosynthetic rules of known peptide hormones, we tried to predict candidate bioactive peptides from human genome structure as peptide ligands for orphan G protein-coupled receptors (GPCRs).2) We developed a program to predict bioactive peptide ligands and predicted 1750 candidate peptides for GPCRs and synthesized them by chemical synthesis.3) To find out new ligands for orphan GPCRs, we measured bioactivity of these synthetic peptides using 26 kinds of cells for detecting changes in their intracellular calcium concentration induced by these peptides.4) We detected 140 peptides, which had activity. However, it was found that all these peptides are active on cells only in a range of high concentrations (more than 10^<-6> M).5) It seemed that candidate peptides crossed-acted on orphan GPCRs and produced a intracellular calcium signal, and it was estimated that these were not true GPCR ligands because known bioactive peptides are active in a concentration range of 10^<-9> -10^<-8> M.6) Further improvement of program software to predict candidate peptides from genome structures is needed, and it seems that development of new screening methods to detect bioactive peptides effectively, in addition to the intracellular calcium assay, is essential.