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 five 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.