Project goal

Validate a streamlined hybrid route to produce semaglutide suitable for pilot‐scale manufacturing, using microwave‐assisted SPPS and site‐selective bioconjugation.

Description of Activities (Stages)

• 1.

  Microwave-Assisted Fragment Synthesis SPPS of peptide segments in a microwave reactor, shortening cycle times, lowering solvent consumption and preserving stereochemical integrity.

• 2.

  Custom Protecting-Group Development Design and laboratory evaluation of bespoke protecting groups to streamline deprotection, eliminate redundant washing steps and reduce chemical waste.

• 3.

  Ligation via Intein Intein-mediated ligation of a synthetic peptide fragment (prepared via microwave- assisted SPPS) to a fermentation-derived peptide chain (which was likewise synthesized via SPPS for the feasibility study), enabling efficient synergy of chemical synthesis and biosynthetic production.

• 4.

  Bill of Materials & Pilot-Scale Technology Assessment Compilation of a detailed BOM.

• 5.

  Process Efficiency & Waste Reduction Implementation of minimal-wash protocols, reduced solvent volumes and inline monitoring of key quality attributes to lower the environmental footprint.

Resources used

Microwave reactor, HPLC, NMR – spectrometers. Relevant chemicals for chemical synthesis of polypeptide chains.

Analytical Confirmation

Analytical verification of a 424 mg test batch of semaglutide against authentic reference material using HPLC retention time.