2010 Fiscal Year Final Research Report

Basic research of new local treatment for inflammatory diseases using molecular-targeting chimera peptide

Research Project

Project/Area Number	21790111
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Single-year Grants
Research Field	Drug development chemistry
Research Institution	Kyoto University
Principal Investigator	KOHNO Masayuki Kyoto University, 大学院・医学研究科, 客員研究員 (00437203)
Research Collaborator	HORIBE Tomohisa 京都大学, 大学院・医学研究科, 特定助教 (20467468)
Project Period (FY)	2009 – 2010
Keywords	医薬分子設計 / ペプチド創薬 / 分子標的 / 局所投与 / DDS
Research Abstract	We investigated the possibility of new powerful therapy for inflammatory diseases using chimera peptides that have a binding sequence to inflammatory cytokine receptors and an adhesion sequence to cell membrane without cytotoxic activity. As a result of pre-survey, we selected TNFα, TLR4, and TGFβ1 as the target molecules, and determined the promising candidates among various antagonist peptides and chimera peptides by the in vitro assay systems. Inhibitory effect of TNFα-antagonist peptide was increased by chimera conjugation with a membrane-adhesion sequence. Local treatment of TGFβ1-antagonist peptide by intratracheal nebulization decreased the levels of fibrotic factors in lung tissue in bleomycin-induced lung fibrosis rat model.