OLIVIER LUDEMANN-HOMBOURGER¹, NICOLAS PETITJEAN²
1. Global Director Innovation & Technology, PolyPeptide Group, Strasbourg, France 
2. Project Manager, Ypso-Facto, Nancy, France

Abstract

This article highlights a new way of thinking for the optimization of Peptide Synthesis. The concept is based on numerical tools to assist the peptide chemists for the choice of the manufacturing route. Process development can be shortened without compromising on process performance and robustness, through the development of unique predictive tools and the use of numerical models to better understand the reaction mechanisms.

INTRODUCTION

The field of Solid Phase Peptide Synthesis (SPPS) has boomed over the last decades. This development has been made possible, largely influenced by the chemist’s expertise at the laboratory scale, whose philosophy is still embedded in the industrial processes of peptide synthesis. Indeed, the first needs for peptides in large scale lead to a simple scale-up of laboratory procedures. The growing demand in the peptide market, the development and greater availability of new raw materials (e.g. Fmoc-protected amino acids) together with an increasing competition has brought costs down and allowed the synthesis of peptides at an industrial scale. The overall quest remains producing high-quality peptides at lower costs while meeting customers’ expectations such as reducing solvent consumption (or other environmental impact) without affecting the product quality (1).

Although SPPS has existed for more than five decades, the available literature still does not provide a clear understanding of peptide synthesis concerning the contributions of different fundamental physical and chemical phenomena like chemical kinetics, resin-liquid equ ...