Scalable and Chromatography-Free Synthesis of Efflux Pump Inhibitor Phenylalanine Arginine β-Naphthylamide for Its Validation in Wild-Type Bacterial Strains.

ABSTRACT: Phenylalanine arginine β-naphthylamine, or PAβN, is a C-terminus capped dipeptide discovered in 1999 as an RND-type efflux pump inhibitor (EPI). Since then, PAβN has become a standard tool compound in EPI research and development. Despite this, PAβN lacks a detailed or efficient synthesis, and standard parameters for its use in wild-type bacterial strains are inconsistent or non-existent. Therefore, a scalable and chromatography-free synthesis of PAβN was developed using streamlined traditional solution-phase peptide coupling chemistry. With this procedure, gram scale quantities of PAβN were synthesized alongside analogues and stereoisomers to build a focused library to evaluate simple structure activity relationships. While most analogues were less active than the broadly utilized L,L-PAβ

SUBMITTER: Russo CM 

PROVIDER: S-EPMC10524873 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature