Dissemin is shutting down on January 1st, 2025

Published in

American Chemical Society, Journal of Medicinal Chemistry, 17(56), p. 6719-6731, 2013

DOI: 10.1021/jm400527k

Links

Tools

Export citation

Search in Google Scholar

Live-Fibroblast IR Imaging of a Cytoprotective PhotoCORM Activated with Visible Light

This paper is available in a repository.
This paper is available in a repository.

Full text: Download

Green circle
Preprint: archiving allowed
  • Must obtain written permission from Editor
  • Must not violate ACS ethical Guidelines
Orange circle
Postprint: archiving restricted
  • Must obtain written permission from Editor
  • Must not violate ACS ethical Guidelines
Red circle
Published version: archiving forbidden
Data provided by SHERPA/RoMEO

Abstract

Carbon monoxide releasing molecules (CORMs) are an emerging class of pharmaceutical compounds currently evaluated in several preclinical disease models. There is general consensus that the therapeutic effects elicited by the molecules may be directly. ascribed to the biological function of the released CO. It remains unclear, however, if cellular internalization of CORMs is a critical event in their therapeutic action. To address the problem of cellular delivery, we have devised a general strategy which,entails conjugation of a CO-releasing molecule (here a photoactivated CORM) to the 5'-OH ribose group of vitamin B12. Cyanocobalamin (B12) functions as the biocompatible water-soluble scaffold which actively transports the CORM against a concentration gradient into the cells. The uptake and cellular distribution of this B-12-photoCORM conjugate is demonstrated via synchrotron FTIR spectromicroscopy. measuremente on living cells. Intracellular photoinduced CO release prevents fibroblasts from dying under conditions of hypoxia and metabolic depletion, conditions that may occur in vivo during insufficient blood supply to oxygen-sensitive tissues such as the heart or brain.