New coenzymically-active soluble and insoluble macromolecular NAD+ derivatives.

Reaction in dimethyl sulfoxide of nicotinamide 8-bromoadenine dinucleotide with the disodium salt of 3-mercaptopropionic acid afforded nicotinamide-8-(2-carboxyethylthio)adenine dinucleotide, a new NAD+ analogue functionalized at the adenine C-8 position by an omega-carboxylic side chain. Carbodimide coupling of the latter derivative to high-molecular-weight water-soluble (polyethyleneimine, polylysine) and insoluble (aminohexy)-Sepharose) polymers gave the corresponding macromolecular NAD+ analogues. These derivatives have been shown to be enzymically reducible. The polyethyleneimine analogue showed a substantial degree of efficiency relative to free NAD+ with yeast alcohol dehydrogenase (47%) but a considerably lower one with rabbit muscle lactate dehydrogenase (3%); the polylysine analogue showed a low degree of efficiency with both enzymes (5-6%).

[1]  C. W. Fuller,et al.  NADH Coupled to Soluble Dextran: Synthesis and Properties , 1974 .

[2]  K. Mosbach,et al.  The synthesis of adenine-substituted derivatives of NADP and their potential as active coenzymes and affinity adsorbents. , 1974, European journal of biochemistry.

[3]  C. Brändén,et al.  The conformation of adenosine diphosphoribose and 8-bromoadenosine diphosphoribose when bound to liver alcohol dehydrogenase. , 1975, European journal of biochemistry.

[4]  R. Schwyzer,et al.  Limitations of Affinity Chromatography: Solvolytic Detachment of Ligands from Polymeric Supports , 1974 .

[5]  P. Zappelli,et al.  Synthesis of coenzymically active soluble and insoluble macromolecularized NAD+ derivatives. , 1975, European journal of biochemistry.

[6]  M. Lilly,et al.  The preparation of soluble high molecular weight NAD derivative active as a cofactor. , 1972, Biochimica et biophysica acta.

[7]  R. J. Bauer,et al.  Chemical synthesis and biological activity of 8-substituted adenosine 3',5'-cyclic monophosphate derivatives. , 1971, Biochemistry.

[8]  K. Mosbach,et al.  The preparation and characterisation of a water‐soluble coenzymically active dextran‐NAD+ , 1974, FEBS letters.

[9]  L. Leloir,et al.  [115] Characterization of phosphorus compounds by acid lability , 1957 .

[10]  N. Kaplan,et al.  Characteristics of 8-substituted adenine nucleotide derivatives utilized in affinity chromatography. , 1975, Archives of biochemistry and biophysics.