Please use this identifier to cite or link to this item: https://scholarbank.nus.edu.sg/handle/10635/139523
Title: BEYOND PARP: CHEMICAL BIOLOGY STUDY OF PARP SUBFAMILY AND OPTIMIZATION OF MICROARRAY
Authors: PENG BO
Keywords: PARP, Chemical Biology, Microarray, MSN, High Throughput Screening
Issue Date: 17-Aug-2017
Citation: PENG BO (2017-08-17). BEYOND PARP: CHEMICAL BIOLOGY STUDY OF PARP SUBFAMILY AND OPTIMIZATION OF MICROARRAY. ScholarBank@NUS Repository.
Abstract: Poly (ADP-ribose) polymerases (PARPs) are key enzymes in a variety of cellular processes. Most small-molecule PARP inhibitors developed to date have been against PARP1, and suffer from poor selectivity. We have developed a small molecule microarray (SMM)-based strategy for high-throughput synthesis, screening of more than 1,000 potential bidentate inhibitors against 10 PARPs. Finally we discovered the first bidentate inhibitor of PARP14, which is a poorly characterized PARP subfamily member, but known to be involved in inflammation and cancers. With the encouraging result, we designed and conducted a combination of metabolic incorporation and “bump-hole” strategy, to study the in vivo biological substrates of PARP14 and PARP16. At the same time, we further optimized traditional SMM technology, which was not suitable for cell arrays. By integrating nanoparticle technology with SMM, the new platform (termed as MSN-on-a-chip) resolved several key problems of previously developed methods, and has facilitated phenotypic screening of a 141-member natural product library with mammalian cells.
URI: http://scholarbank.nus.edu.sg/handle/10635/139523
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