Date of Award


Document Type



Santa Clara : Santa Clara University, 2022.



First Advisor

Ian Carter-O'Connell

Second Advisor

Bill Lu


Poly (ADP-ribose) polymerases, PARPs, are comprised of a family of 17 human enzymes that share a conserved catalytic domain that transfers ADP-ribose from nicotinamide adenine dinucleotide (NAD+) to target proteins. While significant proteomic-based efforts in the field have uncovered a host of potential targets for each of the various active PARP enzymes, an outstanding question remains as to what extent proximal versus distal interactions with the protein substrates govern target selection. In this work, we describe the use of tandem mass spectrometry to identify specific residues that are auto-modified in both PARP14 and PARP15 as well as their preferred modification sites on their shared target, PARP13. Peptide fragment screening of these potential proximal sites was performed using TLC-MALDI-TOF to isolate the minimal proximal motifs required for PARP family member-specific labeling. From these efforts, we identified a 6 amino-acid fragment of a PARP14 specific peptide target that retains selective modification. We further describe the chemical modification of this peptide to derive biomimetics that aims to selectively inhibit individual PARP family members specifically PARP14.