New manufacturing process to produce highly uniform resins with excellent performances in Solid Phase Peptide Synthesis
OTHMAN AL MUSAIMI1,2, SIMONA SERBAN3, YAHYA E. JAD1,2, ZHICHAO MA3, ASHISH KUMAR1,2, CHENG JI3, BEATRIZ G. DE LA TORRE2, NATHAN R. EAST3, ALESSANDRA BASSO3*, FERNANDO ALBERICIO1,4*
*Corresponding authors
1. Peptide Science Laboratory, School of Chemistry and Physics, University of KwaZulu-Natal, Durban, South Africa
2. 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
3. Purolite, Llantrisant, United Kingdom
4. CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine and Department of Organic Chemistry,
University of Barcelona, Spain
Abstract
Peptides are an important class of Active Pharmaceutical Ingredients. Thanks to the implementation of the solid phase synthesis methodology pioneered by the Nobel Laureate R. Bruce Merrifield in the 20th century, it is now possible to synthesize peptides with up to forty amino acids in a multi- kilogram scale.
Herein, we describe a new manufacturing process to produce highly uniform resins that can be successfully applied to solid phase peptide synthesis (SPPS). The resins were employed for the synthesis of between 5 and 28mer peptides using either automatic heat-assisted microwave systems or manual mode. Excellent results are reported when PuroSynth™ CTC/S, PuroSynth™ Wang/S, PuroSynth™ Rink Amide/S and PuroSynth™ MBHA/S are used for SPPS.
INTRODUCTION
Fifty years ago, it was unthinkable to consider that chemically synthesized peptides could become part of the drug arsenal. The synthetic methodology available in that time did not allow for the preparation of these compounds at the multi-Kg
scale, with the purity required by the corresponding drug agencies.
This paradigm started to change when, in the 1960s, R. Bruce Merrifield described the solid phase peptide synthesis (SPPS) methodology. Merrifield realized that anchoring the growing peptide chain to an insoluble polymeric support enhances the synthetic process (1).
Today, it is possible to produce multiple Kgs of a 10-40 amino acid peptide for the drug market; as has been the case for many years for so-called small molecules (< 500-700 Da).
As a result, almost 100 peptides are in the market and, more importantly, more than 300 peptides are being evaluated in clinical trials. This assures that in the near future the number of peptide ...
