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J Med Chem. 2013 Sep 12;56(17):6719-31. doi: 10.1021/jm400527k. Epub 2013 Aug 26.

Live-fibroblast IR imaging of a cytoprotective PhotoCORM Activated with Visible Light.

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1
Institute of Inorganic Chemistry, University of Zürich , Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.

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 B12-photoCORM conjugate is demonstrated via synchrotron FTIR spectromicroscopy measurements 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.

PMID:
23927566
DOI:
10.1021/jm400527k
[Indexed for MEDLINE]
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