title: Small alterations in cobinamide structure considerably influence sGC activation.
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.
authors.affiliation: Institute of Organic Chemistry PAS, Kasprzaka 44/52, 01-224 Warsaw (Poland), Fax: (+48) 22-632-6681.
authors.forename: Maciej
authors.initials: M
authors.lastname: Giedyk
authors.forename: Keith
authors.initials: K
authors.lastname: ó  Proinsias
authors.forename: Sylwester
authors.initials: S
authors.lastname: Kurcoń
authors.forename: Iraida
authors.initials: I
authors.lastname: Sharina
authors.forename: Emil
authors.initials: E
authors.lastname: Martin
authors.forename: Dorota
authors.initials: D
authors.lastname: Gryko
mesh_terms: D003038:Cobamides / Q000737:chemistry*; D004789:Enzyme Activation; D006162:Guanylate Cyclase / Q000378:metabolism*; D015394:Molecular Structure
chemical_list: D003038:Cobamides; C017142:cobinamide; D006162:Guanylate Cyclase
keywords: aminolysis; cGMP; cobinamides; soluble guanylyl cyclase; vitamin B12