Solid phase peptide synthesis: new resin and new protecting group.

Abstract

Solid phase peptide synthesis is the common approach used today in synthesizing peptides in a research scale and production. Success in this approach are governed by several factors. These are; (1) the solid support on which synthesis is to be carried out, (2) linker/spacer on which the first amino acid is linked to the support to allow stepwise growth of the peptide chain, (3) protecting groups of amino acids to allow a clean synthesis without disruption of the growing peptide chain and (4) coupling reagents for improved amide bond formation yielding peptides in the shortest amount of time and with the highest quality. The following thesis shows work conducted on some of these aspects. Chapter two is based on the application of a novel resin Fmoc-Rink-Amide PEG Octagel surface resin. Chapter three describes the development of a novel protecting group for histidine amino acid. A new PEG-PS based resin called Octagel has been developed by Aapptec. Fmoc-Rink-Amide Octagel PEG surface resin is a unique highly uniform surface-active resin. To study the resin’s performance, two peptides Aib-enkephalin pentapeptide and Aib-ACP decapeptide were synthesized and results were compared to Polystyrene and ChemMatrix resins. Swelling and microscope imaging studies were also conducted on each of the resins to highlight their performance associated with Solid Phase Peptide Synthesis. Results have demonstrated that Octagel resin has the potential to synthesize peptide sequences with high purity and therefore to be a good alternative to those currently in the market. Histidine is an important amino acid used in SPPS. It contains a reactive imidazole side group that can cause side reactions in SPPS if left unprotected. Fmoc-based SPPS is the most commonly used strategy in synthesizing peptides today. A protecting group was created for Fmoc-Histidine. SPPS was carried out on the protected histidine and results show that the group is stable in acidic conditions.