| 現在までの達成度 (区分) |
現在までの達成度 (区分)
1: 当初の計画以上に進展している
理由
In the first year of my JSPS DC2 fellowship, I focused on ribosomally constructing a bicyclic DRP library with globular conformation using protected cysteines and successfully screened the library against mouse asialoglycoprotein receptor (mASGR) using in vitro selection. Since it’s our first time to control the complicated disulfide conformation during in vitro translation, the original plan that I set for the first year was to establish and optimize the selection system for bicyclic DRP library, however, even under the condition of reduced working time due to COVID-19, I’ve finished the real selection and successfully obtained a target binding bicyclic peptide with designed structure. Furthermore, I’m moving on to evaluation of the binding peptide with cell-internalization experiments.
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| 今後の研究の推進方策 |
After successfully constructing and selecting the bicyclic library, I'm moving on to designing a constrained tricyclic DRP library with the desired knotted disulfide connectivity. In addition to Acm group, an orthogonal cysteine protecting group, phenylacetamidomethyl (Phacm), will be introduced to facilitate the stepwise deprotection and formation of 2 disulfide bonds. The library will be screened against therapeutic target proteins and the target-binding peptides will be chemically synthesized. Their disulfide connectivity and peptide conformation will be determined by LC-MS and their bioactivities will be evaluated by biological assays.
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