Joseph Denby from CPC Scientific delivered this presentation on green approaches to peptide manufacturing, focusing on sustainable practices in peptide synthesis and oligonucleotide conjugation. He began by introducing peptide-oligonucleotide conjugates (POCs), which are effective for targeting cancer cells and delivering therapeutic components. These conjugates offered advantages such as enhanced tissue penetration, reduced toxicity, and improved pharmacokinetics.
Denby outlined the 12 principles of green chemistry, emphasising the importance of reducing waste and hazardous materials in chemical processes. He highlighted solid phase peptide synthesis (SPPS) as a method that offers benefits over liquid phase synthesis but requires protection of certain amino acids. Minimising protection could enhance atom economy and reduce the use of hazardous solvents.
Two case studies demonstrated minimal protection strategies in SPPS. The first case study involved the synthesis of a peptide-small molecule conjugate, comparing solvent utilisation and atom economy between standard SPPS and minimal protection SPPS. The second case study showcased the synthesis of a goserelin peptide API impurity, using unprotected side chains of histidine, tryptophan, and arginine.
Denby discussed conjugation strategies, particularly the use of click chemistry for POC assembly. He explained how mild conditions and copper-free methods could be employed for effective conjugation. The presentation also explored the advantages of macrocyclic peptides, including enhanced stability and binding affinity, and various cyclisation methods.
