Efficient Microwave-Enhanced Solid Phase Peptide Synthesis of Secretin Hormones Amenable for Rapid Library Design and Lead Optimization
Year: 2026
Type: preprint
Abstract: Microwave-enhanced solid phase peptide synthesis of complex, therapeutically relevant, aspartimide-prone secretin hormones was achieved under optimized conditions with economical and commercially available protected amino acids. In order to determine robust and general methods, standard Fmoc SPPS conditions, Oxyma-buffered deprotection solution, Fmoc-(Dmb)Gly-OH, Fmoc-Asp(OMpe)-OH, and combinations thereof were systematically evaluated for crude purity using LC-MS. Aspartimide formation was significantly reduced, and syntheses were completed in a single run without the need for expensive, commercially inaccessible, or diversity-limiting peptide fragments or pseudoprolines, supplying methods amenable for rapid library generation, hit-to-lead endeavors, and lead optimization.
Source: ChemRxiv
Institution: Purdue University West Lafayette
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7220711914