Gilles Goetz
Pfizer, USA
Title: EPSA: A Novel Supercritical Fluid Chromatography Technique Enabling the Design of Permeable Cyclic Peptides
Biography
Biography: Gilles Goetz
Abstract
Applications of a new chromatographic method using SFC technology developed recently at Pfizer are described here. The EPSA method, as readout of polarity, correlates retention on a specific stationary phase with the exposed polarity of a molecule. Changes in retention can be interpreted by changes in polarity induced by the presence of Intra-molecular Hydrogen Bonding (IMHB): indeed, IMHBs tend to impact molecular conformation, inducing hidden polarity that results in a decrease in analyte retention on the EPSA support. We demonstrate here the impact of this method on multiple Beyond Rule of 5 projects (NS5A, Oxytocin Receptor, CXCR7 Modulator, others). Given that conformational changes (induced and/or stabilized by the formation of IMHB) increases potential for membrane permeability, we show here that EPSA, and the EPSA prediction model, have significant impact in peptide drug design.