Synthesis of Ser-Ala-Ala Cyclic Desmosine

Abstract

Elastin is present in the extracellular matrix of various tissues, most abundantly in the aorta and major vascular vessels, and is formed by self-assembly followed by concomitant crosslinkers of tropoelastin, an elastin precursor. Desmosine is a pyridinium-based tetrafunctional amino acid that serves as an important crosslinker to bind the polymeric chains of peptides in the 3D network of elastin. Despite its significance, the detailed structure of elastin has not been elucidated. In this work, we report the synthesis of a cyclic desmosine peptide designed to mimic elastin, which could serve as a compound for mass spectrometric analysis to elucidate crosslinking structures. The synthesis involved stepwise and regioselective palladium-catalyzed cross-couplings, and inter- and intramolecular condensations.