Ultrasonication is a low-cost and eco-friendly source of energy that in chemistry (sonochemistry) has been widely applied in both homogenous and heterogeneous reactions.1 To date, very few examples of sonochemical-assisted transformations in solid-phase peptide synthesis (SPPS), a heterogeneous reaction system par excellence, have been reported.2 Herein, we demonstrated that ultrasonication can improve the performance of SPPS,3 by providing evidence that it reduces both reaction time (up to 93% compared to standard protocols) and reagent equivalents (up to 50% compared to standard protocols) required to assembly peptides on the solid support, without exacerbating the main side reactions, such as aspartimide formation and racemization. Moreover, we decoupled the role of the heating and sonication in accelerating the reaction rates, excluding that the observed beneficial effects were ascribable to the ultrasound-related increment of reaction temperature. Our study culminated in the setting of an ultrasonication assisted method for SPPS (US-SPPS), whose reliability was tested on the synthesis of peptides endowed with “difficult sequences”, including Aib-Enkephaline, ACP 65-74, JR-10 and αβ 1-42, which are commonly employed as standards to validate new synthetic SPPS protocols. Altogether, our results place the US-SPPS among the current high-efficient peptide synthetic strategies, encouraging the extensive application of low-frequency ultrasounds to SPPS to further unveil the potential of their cooperation.

Boosting solid-phase peptide synthesis by ultrasonication

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.