Application of the highly sensitive labeling reagent to the structural confirmation of readily isomerizable peptides

AbstractThioamycolamide A (1) is a biosynthetically unique cytotoxic cyclic microbial lipopeptide that bears ad-configured thiazoline, a thioether bridge, a fatty acid side chain, and a reduced C-terminus. It has gained attention for its unique structure, and very recently we reported the total synthesis of1 via a biomimetic route. The NMR spectra of synthetic1 agreed with those of natural1. However, structural identity between peptidic natural and synthetic compounds is often difficult to confirm by comparison of NMR spectra because their NMR spectra vary depending on the conditions in the NMR tube, which often result in the structural misassignment of peptidic compounds. Especially, our total synthesis based on the putative biomimetic route potentially gives1 as a diastereomixture at the final step. The problem is that the diastereomers of peptidic mid-sized molecules often exhibit similar properties (such as NMR spectra and bioactivities), and their separation procedures are often laborious. Herein we report the structural confirmation of synthetic1 by the LC –MS-based chromatographic comparison with the use of our highly sensitive labeling reagentl-FDVDA; the highly sensitive-advanced Marfey ’s method (HS-advanced Marfey’s method). This work demonstrated the utility of our highly sensitive labeling reagent for the structural determination of not only scarce natural products but also readily isomerizable synthetic compounds.

Source: Journal of Natural Medicines - January 2, 2021 Category: Drugs & Pharmacology Source Type: research