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SSPC Impact Case Study: Sustainability

Solid-Phase Synthesis of Peptides and Conjugates

Project Lead:

Prof. Marc Devocelle, Royal College of Surgeons Ireland

Project Partner:

MSD

Areas of Impact:

Economic, Environmental, Health

Scientific Domains:

Small Molecule / Drug Product

Lead
Solid Phase Peptide Synthesis (SPPS) is best positioned to meet the need for synthetic peptides, which represent one of the fastest growing classes of new drugs. However, its sustainability on an industrial scale is threatened by its reliance on organic solvents such as DMF and NMP, both placed on the Candidate REACh List of substances of very high concern for Authorisation. Led by Prof. Marc Devocelle, the greenest option for SPPS, aiming for its implementation in aqueous media, is investigated in this project through the development of a protection and coupling strategies compatible with this solvent.

Aim
The overall aim of this project is to investigate new methods in peptide chemistry, which can contribute in addressing some of the current shortcomings and needs of synthetic peptides and their conjugates.

Objectives
The main research objectives of this project are to develop methods which: 1) improve the sustainability of Solid Phase Peptide Synthesis (SSPS); complement techniques of peptide conjugation/modification and circumvent some of their limitations, for the preparation of 2) drug conjugates; 3) lipidated sequences; 4) polymer conjugates.

SPPS is best positioned to meet the need for synthetic peptides, which represent one of the fastest growing classes of new drugs, but is currently not sustainable on an industrial scale. Its main limitation is a reliance on organic solvents already placed on the REACh list of undesirable substances. The greenest option for SPPS, aiming its implementation in aqueous media, necessitate the development of a protection and coupling strategies compatible with this solvent. These are investigated through the replacement of the N-protecting group 9-fluorenylmethyloxycarbonyl (Fmoc) by a sulfonyl-based N-protection, in conjunction with the use of N-carboxyanhydrides (NCAs), as a coupling reagent-free chemistry.

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