Peptide ligand screening of transthyretin protein-protein interaction inhibitor using phage display system

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K18875
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: Kumamoto University
• Principal Investigator: SATO Takashi 熊本大学, 大学院生命科学研究部(薬), 助教 (70555755)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: トランスサイレチン / 家族性アミロイドポリニューロパチー / ファージディスプレイ

Outline of Final Research Achievements

Familial Amyloidotic Polyneuropathy (FAP) is one of the systemic amyloidosis, which is caused by a point mutation in transthyretin (TTR). Because mutant TTR forms amyloid fibrils after secretion from the cells, we believed that secretory inhibition of mutant TTR followed by their intracellular degradation could be a potential drug target for FAP. We previously demonstrated that inhibition of TTR tetramerization in the endoplasmic reticulum blocks secretion of mutant TTR. In this study, we aimed to determine peptides that could inhibit TTR tetramerization using the phage display system. Here, we identified three cyclic peptides that bind to TTR. Two of the three peptides could destabilize conformations of tetrameric and monomeric TTRs.

Free Research Field

生物系薬学