Enabling faster and greener peptide purification in discovery chemistry

Abstract

Peptides are attracting broad interest across the pharmaceutical industry owing to their vast therapeutic potential for drugging high-value targets and flexible dosing and formulation options to improve patient access. As the industry increases focus on peptide-based discovery programs, fast, high-throughput, and green purification methods have become increasingly valuable. Due to the vast sequence and physicochemical diversity of peptides, expedited purification of large libraries has remained a challenge. Herein, we describe the development of a High-Throughput Purification (HTP) approach for peptides wherein each purification is achieved in 6 min or less, representing a substantial reduction in time and solvent consumption compared with conventional methods, all while maintaining high purity levels. This approach relies on Reversed-Phase High-Performance Liquid Chromatography (RP-HPLC), leveraging a dual pump preparative system and short focused solvent gradients to reduce purification times and achieve highly efficient and accelerated high-throughput purification.