Elucidation of pharmacological effects of antibiotics against genetic diseases caused by nonsense mutations and development of new therapeutic agents

2016 Fiscal Year Final Research Report

• Project/Area Number: 26860025
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Physical pharmacy
• Research Institution: Sophia University
• Principal Investigator: Kondo Jiro 上智大学, 理工学部, 准教授 (10546576)
• Research Collaborator: Hanessian Stephen モントリオール大学, 教授 ; Baasov Timor テクニオン・イスラエル工科大学, 教授 ; Ennifar Eric フランス国立科学研究機構, 研究部長 ; Auffinger Pascal フランス国立科学研究機構, 研究部長
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: ナンセンス変異型遺伝性疾患 / 抗生物質 / リボソーム / Ｘ線結晶解析 / ドラッグデザイン

Outline of Final Research Achievements

In order to develop new therapeutic agents against genetic diseases, I have performed structural studies of the ribosomal RNA molecular switches of several different organisms/cells by X-ray analysis and have designed and synthesized new drug compounds based on the obtained structural data. We have succeeded to design and synthesize several compounds possessing high readthrough, antiprotozoal or antibacterial activity and less toxicity against human. Especially, one of the designed/synthesized fluorinated aminoglycosides specifically binds to the RNA molecular switches of eukaryote and antibiotic-resistant bacteria. This compound can be a potent therapeutic agent against genetic diseases caused by nonsense mutations.

Free Research Field

構造生命科学