The coenzyme A biosynthetic pathway: A new tool for prodrug bioactivation

Arch Biochem Biophys. 2019 Sep 15:672:108069. doi: 10.1016/j.abb.2019.108069. Epub 2019 Aug 9.

Abstract

Prodrugs account for more than 5% of pharmaceuticals approved worldwide. Over the past decades several prodrug design strategies have been firmly established; however, only a few functional groups remain amenable to this approach. The aim of this overview is to highlight the use of coenzyme A (CoA) biosynthetic enzymes as a recently explored bioactivation scheme and provide information about its scope of utility. This emerging tool is likely to have a strong impact on future medicinal and biological studies as it offers promiscuity, orthogonal selectivity, and the capability of assembling exceptionally large molecules.

Keywords: Bioactivation; Coenzyme A; Pantothenamide; Pantothenate; Prodrug.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Infective Agents / metabolism
  • Anti-Infective Agents / pharmacology
  • Coenzyme A / biosynthesis
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology*
  • Pantothenic Acid / analogs & derivatives*
  • Pantothenic Acid / metabolism
  • Pantothenic Acid / pharmacology*
  • Phosphotransferases (Alcohol Group Acceptor) / chemistry
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Prodrugs / metabolism
  • Prodrugs / pharmacology*
  • Proof of Concept Study
  • Substrate Specificity

Substances

  • Anti-Infective Agents
  • Enzyme Inhibitors
  • Prodrugs
  • Pantothenic Acid
  • Phosphotransferases (Alcohol Group Acceptor)
  • pantothenate kinase
  • Coenzyme A

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