A versatile strategy for the design and synthesis of novel ADP conjugates and their evaluation as potential poly(ADP-ribose) polymerase 1 inhibitors

Yuliya V. Sherstyuk, Alexandra L. Zakharenko, Mikhail M. Kutuzov, Polina V. Chalova, Maria V. Sukhanova, Olga I. Lavrik, Vladimir N. Silnikov, Tatyana V. Abramova

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Abstract: A versatile strategy for the synthesis of NAD + mimetics was developed, involving an efficient pyrophosphate linkage formation in key conjugates containing a functional amino group which acts as useful reactive anchor for further derivatization. These NAD + mimetics consist of ADP conjugated through a diphosphate chain to an extended aliphatic linker bearing an aromatic acid residue. A number of conjugates containing aromatic carboxylic acids were found to inhibit poly(ADP-ribose) synthesis catalyzed by poly(ADP-ribose) polymerase-1 (PARP-1). A new class of potential PARP-1 inhibitors mimicking NAD +, a substrate in the PARP-1 catalyzed reaction, was proposed. Graphical Abstract: [Figure not available: see fulltext.]

Original languageEnglish
Pages (from-to)101-113
Number of pages13
JournalMolecular Diversity
Volume21
Issue number1
DOIs
Publication statusPublished - 1 Feb 2017

Keywords

  • NAD analogues
  • PARP inhibitors
  • PARP-1
  • Pyrophosphate synthesis
  • NAD/chemistry
  • Poly (ADP-Ribose) Polymerase-1/antagonists & inhibitors
  • Chemistry Techniques, Synthetic
  • Biomimetic Materials/chemical synthesis
  • Drug Design
  • Adenosine Diphosphate/chemistry
  • Enzyme Inhibitors/chemical synthesis
  • ACID
  • CHROMATIN
  • NICOTINAMIDE
  • PROBING BINDING REQUIREMENTS
  • STRUCTURAL-ANALYSIS
  • FUNCTIONALIZATION
  • REPAIR
  • DNA
  • NAD ANALOGS
  • NAD(+) analogues
  • PARP INHIBITORS

Fingerprint

Dive into the research topics of 'A versatile strategy for the design and synthesis of novel ADP conjugates and their evaluation as potential poly(ADP-ribose) polymerase 1 inhibitors'. Together they form a unique fingerprint.

Cite this