OTHMAN AL MUSAIMI^1,2, BENJAMIN D. SUMMERS³, MAHAMA ALHASSAN^1,2, BEATRIZ G. DE LA TORRE¹, FERNANDO ALBERICIO^2,4* SIMONA SERBAN³, ALESSANDRA BASSO³*
*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, Llantrisant, United Kingdom 
4. CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine and Department of Organic Chemistry, University of Barcelona, Barcelona, Spain

Abstract

Solid-phase peptide synthesis has become an important technique as the method of choice to deliver high quality peptide entities at both laboratory and production scale. The polymeric support (i.e. the resin) is the most essential part of the process as it covalently holds the growing peptide through the various synthetic steps. Several key features of the resin must be addressed before initiation of the synthesis to ensure successful generation of the desired peptide. In this paper, several PuroSynthTM peptide synthesis resins were examined for a range of aspects including morphological characteristics, mechanical stability and distribution of functional groups. Additionally, to demonstrate the effect of these aspects, the Purosynth™ CTC resin was used to synthesise a heptapeptide analogue to the antibiotic darobactin with >95 % purity.

INTRODUCTION

Peptides have reached an important status among drugs authorized by the corresponding regulatory agencies, mainly the U.S. Food and Drugs Administration and the European Medicines Agency. Currently, more than 80 peptides are in the market from simple dipeptides to large peptides containing more than 40 amino acids.

The key to the approval of medium and large peptides by the agencies was the development of the solid phase peptide synthesis (SPPS) technology by Merrifield (1).  Although the synthesis can be achieved on a large and diverse class of solid supports, the polystyrene (PS) resin is the only one suitable for production in large batches while fulfilling the requirements of good manufacturing practice (GMP) associated with active pharmaceutical ingredient generation.

The most important factor in determining the optimization of the SPPS, and therefore the success of a production campaign, is the support. Herein, the efforts carried out for the manufacture of PS resins and the quality control required to ensure their best performance is discussed.

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