Peptide are a promising class of therapeutics due to their high selectivity and efficacy while being safe and tolerated by the body in relation to many small molecule counterparts. With several high revenue peptide-based drugs on the market and a library of potential candidates, there is a great demand for highly robust and efficient synthetic methods. Microwave assisted SPPS has established itself as the primary chemical method to produce high quality peptides while drastically reducing synthesis time and waste. Recent developments in the area of microwave assisted SPPS has drastically reduced synthesis time and waste while improving peptide purities and yields. Here, we will a review of current and recent methodology, as well as recent development efforts of highly active, universal resins for preparing C-terminal peptide acids.<br/> <br/>Key features of the improved methodology include increased purity and suppressed side reactions, simple synthetic parameters for standard and non-standard (cyclic, branched, stapled, etc.) sequences, one-pot coupling and deprotection processes, and reduction of up to 95% generated waste when compared to conventional methods. Together, these features reduce entire cycle times to under 3 minutes, allowing for difficult 10-mer peptides to be synthesized within 30 minutes with less than 100 mL waste. The hyper-acid sensitive Cl-TCP linker expands the application of this technology, providing unique stability and protection against C-terminal side reactions at elevated temperatures compared to well-known 2-Cl-Trt and Trityl (TCP) linkers.

Recent developments in microwave-assisted SPPS

ACS Spring Meeting 2021

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