OTHMAN AL MUSAIMI^1,2, BENJAMIN D. SUMMERS³, ALESSANDRA BASSO³, BEATRIZ G. DE LA TORRE¹, FERNANDO ALBERICIO^2,4* SIMONA SERBAN³*
*Corresponding authors
1. KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
2. Peptide Science Laboratory, School of Chemistry and Physics, University of KwaZulu-Natal, Durban, South Africa
3. Purolite, Unit D Llantrisant Business Park, United Kingdom
4. CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine and Department of Organic Chemistry, University of Barcelona, Spain

Abstract

In recent years, peptides have gained an important position in the drug arena for a variety of treatments. Solid-phase peptide synthesis (SPPS) continues to have a significant impact in both R&D as well as in production of commercial peptides. The combination of SPPS with reverse-phase (RP) chromatographic separations allowed for the peptides to be purified to levels suitable for drug usage.

Thanks to their chemical and physical stability to high pressure, chemicals, temperature and oxidising reagents, polystyrene / divinyl benzene (PS/DVB) resins are the main solid support for peptide synthesis as well as being suitable for the chromatographic purification of the peptides by RP and ion exchange (IEX). Depending on the application, the optimal cross-linking changes, as do the optimal particle size, the uniformity in particle size distribution and the porosity of the resin. The characteristics and applications of the PS/DVB resins are explored in this paper for the synthesis and purification of peptides of commercial interest.

INTRODUCTION

Peptides are becoming an important class of Active Pharmaceutical Ingredients (APIs). When the Nobel Laureate Vincent Du Vigneaud reported in 1954 (1), the first synthesis of a peptide with biological activity,  oxytocin, few analysts had predicted that today peptides would constitute 5-10% of the new chemical entities accepted by the FDA each year (2). The excellent properties of peptides, such as high activity and specificity, low toxicity, low accumulation in tissues, minimization of drug-drug interactions, biological and chemical diversity are sufficient to justify the importance of peptides in the drug arena.

Two factors proved crucial in the materialization of peptides as drugs. First, it was the development of the solid-phase peptide synthesis (SPPS) methodology by the Nobel Laureate R. Bruce Merrifield (3). SPPS technology signified a revolution in the field due to the possib ... ...