Small Alterations in Cobinamide Structure Considerably Influence sGC Activation |
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Authors: | Maciej Giedyk Dr. Keith ó Proinsias Sylwester Kurcoń Dr. Iraida Sharina Dr. Emil Martin Prof. Dorota Gryko |
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Affiliation: | 1. Institute of Organic Chemistry PAS, Kasprzaka 44/52, 01‐224 Warsaw (Poland), Fax: (+48)?22‐632‐6681;2. Department of Internal Medicine, Division of Cardiology, University of Texas Health Science Center in Houston, 1941 East Road, Houston, TX 77054 (USA) |
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Abstract: | Specially designed B‐ring‐modified cobalamin derivatives were synthesized and tested as potential activators of soluble guanylyl cyclase (sGC). Herein, we disclose the influence of substituents at the c‐ and d‐positions in hydrophilic and hydrophobic cobyrinic acid derivatives on their capacities to activate sGC. The presence of the amide group at c‐/d‐position in cobyrinic acid derivatives strongly influence the level of sGC activation. Removal of the d‐position altogether has a profound effect for hydrophobic compounds. In contrast, little differences were observed in hydrophilic ones. |
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Keywords: | aminolysis cGMP cobinamides soluble guanylyl cyclase vitamin B12 |
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