Automated Synthesis of Heavily Phosphorylated Peptides. Issue 26 (13th July 2021)

• Record Type: Journal Article
• Authors: Grunhaus, Dana; Friedler, Assaf; Hurevich, Mattan
• Is Part Of: European journal of organic chemistry. Issue 26(2021)
• Page Start: 3737
• Page End: 3742
• Publication Date: 2021-07-13
• Subjects: Automated synthesis -- Heavily phosphorylated peptide -- Phosphorylation pattern -- SPPS; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.202100691
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract: Multi phosphorylated peptides are key tools in understanding the biological roles of protein phosphorylation patterns. In this work, we focused on multi phosphorylated peptides with over four, clustered, phosphorylation sites that are termed herein heavily phosphorylated peptides (HPPs). The synthesis of heavily phosphorylated peptides is extremely difficult and requires the use of a wide temperature range. Standard peptide synthesizers are incapable of both cooling and heating, which impedes the automated synthesis of those peptides. Herein, we used the oligosaccharide synthesizer Glyconeer 2.1 to develop a protocol for the automated synthesis of heavily phosphorylated peptides. The Glyconeer 2.1 is able to both cool and heat, which enabled the development of highly controlled coupling and deprotection conditions that were used for the automated synthesis of four different heavily phosphorylated peptides with five or more, clustered, phosphorylation sites. Our approach paves the way for an easy automated synthesis of a variety of heavily phosphorylated peptides. Abstract : The Glyconeer 2.1, originally developed for oligosaccharides assembly, was transformed into a unique phosphopeptide synthesizer utilizing tight temperature control to provide peptides with five, seven, and nine clustered phosphorylation sites in an entirely automated fashion.