New Technologies for Sustainable Peptide Syntheses
Symposium Organizers: Michael Kopach, Senior Research Advisor, Synthetic Molecule Design and Development, Lilly
Co-Sponsor: ACS Green Chemistry Institute Pharmaceutical Roundtable
The first therapeutic synthetic peptide oxytocin was introduced in 1962, and as of 2020 over 60 peptide drugs have been approved in the U.S., Europe and Japan, more than 150 drugs are currently in active clinical development, and >260 have been tested in human clinical trials. Peptides have gained increased interest as therapeutics over the past few decades, largely due to their advantageous properties including high specificity and affinity, as well as superior safety and tolerance. Merrifield’s landmark invention of solid-phase peptide synthesis (SPPS) consisting of anchoring and growing the peptide on polymetric solid support has enabled the synthesis of longer peptides that were previously unobtainable and allows for facile incorporation of non-coded components. However, recent studies have revealed that at least 10 metric tons of solvent and materials are used to synthesize 1 kg of peptide drug substance produced by SPPS which is orders of magnitude higher than most small molecule syntheses. In addition, many of the reagents and solvents utilized in peptide syntheses are classified as environmentally problematic substances by the ECHA (European Chemicals Agency) under the REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals) regulation. Current and impending regulation by REACH could result in future disruption of industrial production of therapeutic peptides.
Recognizing the unmet environmental needs the ACS Green Chemistry Institute Pharmaceutical Roundtable recently founded a team focused on improving sustainability practices in peptide development and has funded academic research over the past five years. The groups initial contribution is focused on stimulating innovations in peptide syntheses (J. Org. Chem., 2019, 84 (8), pp 4615–4628).
Several new technologies are now in development to address these unmet environmental needs such as tag assisted liquid phase peptide synthesis, chemoenzymatic peptide synthesis, alternative purification strategies and use of green solvents. The aim of this session is to highlight some of the recent developments in these areas and the potential benefits they bring to peptide sustainability. We invite abstracts on the topic of improving peptide sustainability from interested parties in academia and industry.