HUSCAP logo Hokkaido Univ. logo

Hokkaido University Collection of Scholarly and Academic Papers >
Faculty of Pharmaceutical Sciences >
Peer-reviewed Journal Articles, etc >

Discovery of Biologically Optimized Polymyxin Derivatives Facilitated by Peptide Scanning and In Situ Screening Chemistry

Files in This Item:
TDA scanning_2023-01-13-1.pdf2.23 MBPDFView/Open
Please use this identifier to cite or link to this item:

Title: Discovery of Biologically Optimized Polymyxin Derivatives Facilitated by Peptide Scanning and In Situ Screening Chemistry
Authors: Kaguchi, Rintaro Browse this author
Katsuyama, Akira Browse this author →KAKEN DB
Sato, Toyotaka Browse this author →KAKEN DB
Takahashi, Satoshi Browse this author
Horiuchi, Motohiro Browse this author →KAKEN DB
Yokota, Shin-ichi Browse this author
Ichikawa, Satoshi Browse this author →KAKEN DB
Issue Date: 28-Jan-2023
Publisher: American Chemical Society
Journal Title: Journal of the American Chemical Society
Volume: 145
Issue: 6
Start Page: 3665
End Page: 3681
Publisher DOI: 10.1021/jacs.2c12971
Abstract: Peptides can be converted to highly active compounds by introducing appropriate substituents on the suitable amino acid residue. Although modifiable residues in peptides can be systematically identified by peptide scanning methodologies, there is no practical method for optimization at the scanned position. With the purpose of using derivatives not only for scanning but also as a starting point for further chemical functionalization, we herein report the scanning and direct derivatization strategy through chemoselective acylation of embedded threonine residues by a serine/threonine ligation (STL) with the help of in situ screening chemistry. We have applied this strategy to the optimization of the polymyxin antibiotics, which were selected as a model system to highlight the power of the rapid derivatization of active scanning derivatives. Using this approach, we explored the structure-activity relationships of the polymyxins and successfully prepared derivatives with activity against polymyxin-resistant bacteria and those with Pseudomonas aeruginosa selective antibacterial activity. This strategy opens up efficient structural exploration and further optimization of peptide sequences.
Rights: This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of the American Chemical Society, copyright c American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see
Type: article (author version)
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 勝山 彬

Export metadata:

OAI-PMH ( junii2 , jpcoar_1.0 )

MathJax is now OFF:


 - Hokkaido University