Employing complementary spectroscopies to study the conformations of an epimeric pair of side-chain stapled peptides in aqueous solution.

ABSTRACT: Understanding the conformational preferences of free ligands in solution is often necessary to rationalize structure-activity relationships in drug discovery. Herein, we examine the conformational behavior of an epimeric pair of side-chain stapled peptides that inhibit the FAD dependent amine oxidase lysine specific demethylase 1 (LSD1). The peptides differ only at a single stereocenter, but display a major difference in binding affinity. Their Raman optical activity (ROA) spectra are most likely dominated by the C-terminus, obscuring the analysis of the epimeric macrocycle. By employing NMR spectroscopy, we show a difference in conformational behavior between the two compounds and that the LSD1 bound conformation of the most potent compound is present to a measurable extent in aqueous sol

SUBMITTER: Bogaerts J 

PROVIDER: S-EPMC8694311 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature