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Enhancing the Methyl‐Donor Activity of Methylcobalamin by Covalent Attachment of DNA
Author(s) -
Fasching Mario,
Perschinka Hannes,
Eichmüller Christian,
Gschösser Sigrid,
Kräutler Bernhard
Publication year - 2005
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.200590001
Subject(s) - methylcobalamin , chemistry , aqueous solution , covalent bond , conjugate , nucleophile , corrinoid , stereochemistry , vitamin b12 , medicinal chemistry , dna , organic chemistry , catalysis , methyltransferase , methylation , biochemistry , mathematics , mathematical analysis
The preparation of a covalent DNA conjugate of vitamin B 12 by means of heterogeneous solid‐phase synthesis is reported. The cyano‐corrinoid made available, dipotassium Co β ‐cyanocobalamin‐(3″→2′),(3″→5′)‐bis‐2″‐deoxythymidyl‐3″‐ate (K 2 ‐ 4 ), was cleanly methylated at the Co center by electrosynthetic means. Aqueous solutions of the resulting organometallic DNAB 12 conjugate K 2 ‐ 5 exhibited spectroscopic properties indicative of significant weakening of the axial (CoN) bond, together with a 25‐times higher basicity relative to Co β ‐methylcobalamin ( 2 ). Methyl‐transfer equilibria of pH‐neutral aqueous solutions of K 2 ‐ 5 and cob(I)alamin (K‐ 7 ) on one side, and of cob(I)alamin‐(3″→2′),(3″→5′)‐bis‐2″‐deoxythymidyl‐3″‐ate (K 3 ‐ 8 ) and methylcobalamin ( 2 ) on the other, were studied at room temperature ( Scheme 3 ). The NMR‐derived data provided an equilibrium constant of ca. 0.3. Activation of K 2 ‐ 5 for abstraction of its Co‐bound Me group by a nucleophile (such as cob(I)alamin) was, thus, indicated.