Progress Towards a Method for the Solid Phase Synthesis of Pyrophosphorylated Peptides

Abstract

Pyrophosphorylation has been identified as a posttranslational modification(PTM) that is thought to control important cellular functions such as insulin signaling and fat accumulation. In order to fully understand the effects of this PTM, it is necessary to have methods, such as affinity reagents or mass spectrometry techniques, to detect and study it in vivo. Synthetic pyrophosphorylated peptide sequences are necessary for the development of these techniques. This thesis focuses on synthesizing a solid-phase peptide synthesis (SPPS) compatible pyrophosphoserine that could be used to synthesize such peptide sequences. A mono-β-benzyl pyrophosphoserine analog was synthesized in order to study the chemical stability of the mono-β-benzyl pyrophosphate moiety in SPPS resin cleavage and Fmoc-deprotection conditions. The stability studies show that a pyrophosphoserine could be stable under SPPS conditions. A synthetic approach to an Fmoc-protected pyrophosphoserine was developed. This amino acid is to be incorporated in peptide sequences through SPPS.