Projects / Synthetic strategies / Optimized strategies for the synthesis of bio molecules

Innovative methodologies in SPPS

Profiles

Efficiency and speediness represent critical factors for the growing demand of synthetic peptides by combinatorial and medicinal chemistry, strongly affecting the process of drug discovery. Solid-phase peptide synthesis (SPPS) represents the leading strategy for peptide synthesis, as confirmed by the rapid progress both in the development of different reagents, such as resins and coupling reagents, and in the technology of instrumentations.

Difficult peptide syntheses can present several complications as result of internal aggregation of resin-bound peptides during elongation steps, reducing reagents penetration, and significantly decreasing reaction rates in both acylation and deprotection steps. Such events strongly affect purity of the crude peptides and therefore, final yield.

Therefore we investigated on the use of alternative synthetic strategies such as using microwave (MW) irradiation or developing new triazine-based coupling reagents (TBCRs) to apply to SPPS of complex peptides. Such methodologies exhibit several advantages improving coupling rates, and as a consequence the synthesis of difficult peptide sequences (i.e. glycosylated, citrullinated, multiple antigenic, amyloidogenic peptides, etc.) in terms of crude purity, final yield, and time-consuming compared to conventional protocols.

A peptide backbone (a) before and (b) during microwave irradiation. Reproduced by permission of The Royal Society of Chemistry and © 2006, CEM Corporation.