18O/16O‐Encoding Strategy for Microscale Stereochemical Determination of Peptidic Natural Products. Issue 17 (16th July 2021)

• Record Type: Journal Article
• Authors: Takeuchi, Aoi; Itoh, Hiroaki; Inoue, Masayuki
• Is Part Of: Chemistry, an Asian journal. Volume 16:Issue 17(2021)
• Page Start: 2447
• Page End: 2452
• Publication Date: 2021-07-16
• Subjects: configuration determination -- natural products -- peptides -- solid-phase synthesis -- stable isotope labeling; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/asia.202100674
• Languages: English
• ISSNs: 1861-4728

Abstract

Abstract: The demand for more efficient methods of establishing the undetermined stereochemistries of peptidic natural products continues unabated. A new method for microscale stereochemical determination was devised by integrating solid‐phase synthesis, split‐and‐mix randomization, 18 O/ 16 O‐encoding of d /l ‐configurations, tandem mass spectrometry, and biological evaluation. Here we applied gramicidin A as the molecule for a blind test. Gramicidin A and its 31 diastereomers were randomly prepared in microgram scale with 18 O/ 16 O‐stereochemical encoding and subjected to MS/MS‐structural determination and cytotoxicity assay. Only the parent gramicidin A was selected from among the 32 stereoisomers, validating the high reliability of the present strategy. Abstract : A novel 18 O/ 16 O‐encoding strategy for microscale stereochemical determination of peptidic natural products has been devised. The strategy integrates the one‐bead‐one‐compound (OBOC) strategy, 18 O/ 16 O‐stereochemical encoding, tandem mass (MS/MS) spectrometry, and biological evaluation. Its application enabled the correct identification of gramicidin A from 32 stereoisomers randomly prepared in microgram scale, thereby validating the high reliability.