Organic Chemistry — Prelim Defense

About the event

Speaker: Ryanne Ballard

Group: Prof. Berkman

Title: Traceless Phosphoryl Mediated Isopeptide Crosslinking

Abstract: The phosphorylation of canonical Tyr, Thr, and Ser (pTyr, pThr, pSer) residues following dysregulation of kinase activity have been well documented in a wide variety of cancer types. However, recent studies regarding environmental organophosphorus (OP) toxicants suggest that the phosphorylation of Glu, Asp, and Lys (pGlu, pAsp, pLys) serve as the initiator to inter- and intra-molecular isopeptide crosslinking in proteins. Due to these non-canonical phosphorylation marks being dislodged following the crosslinking events between Glu/Asp residues and their neighboring Lys residues, they are considered “traceless adducts”, but their impact on cancer risk remains unknown. While phosphoryl adducts caused by environmental toxicants and those caused by non-specific kinase activity may seem unrelated, it’s reasoned that these processes can result in the same outcome of traceless phosphoryl-mediated isopeptide crosslinks, which can potentially serve as indicators for cancer risk. This proposal will discuss the synthetic methods in which these vulnerable peptide sequences can be prepared and used to probe this unknown mechanism by means of 31P NMR, mass spectrometry, and HPLC. Furthermore, it will focus on the identification of peptide sequences exceptionally vulnerable to these traceless crosslinking interactions.