Integration of C-Acylation in the Solid-Phase Synthesis of Peptides and Peptidomimetics Employing Meldrum’s Acid, Phosphorus, and Sulfur Ylides

Abstract

Modification of native peptides to peptidomimetics is an important goal in medicinal chemistry and requires in many cases the integration of C-acylation steps involving amino acids with peptide synthesis. Many classical C-acylation protocols involving Claisen condensations or the use of ylides are not compatible with peptide synthesis, mostly due to the requirement of strong bases leading to epimerization or deprotection of peptides. Meldrum’s acid as well as several specific phosphorus and sulfur ylides, however, are acidic enough to provide reactive C-nucleophiles at mildly basic conditions tolerated during peptide synthesis. This review provides an overview of peptide-compatible C-acylations of Meldrum´s acid, phosphorus and sulfur ylides and their application in the medicinal chemistry of peptides.

Enhancing activity of food protein‐derived peptides: An overview of pretreatment, preparation, and modification methods

“…O‐acylation entails the attachment of the acyl group to the oxygen atom of a serine or threonine residue within the peptide (Wiktorowicz et al., 2012). Lastly, C‐acylation is the attachment of the acyl group to the sulfur atom of a cysteine residue within the peptide (Ahsanullah et al., 2022). These modifications can improve the functional properties of peptides by altering the charge balance within their structure.…”