Abstract
A convenient two-step synthesis of conjugates of HS-CoA and D-pantetheine with aminooxy analogues of Spm and Spd was suggested. The use of acetone linker provided target conjugates with quantitative yields. The activity of CoA-derived “bisubstrate” inhibitors, being active at microM concentrations, was at least 100 times better than that of corresponding derivatives of D-pantetheine.
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Abbreviations
- CoASH and CoASAc:
-
coenzyme A and its acetyl derivative
- D-Pant:
-
N-(D-pantothenyl)aminoethyl mercaptan
- Put:
-
putrescine (1,4-diaminobutane)
- Spm:
-
spermine (1,12-diamino-4,9-diazadodecane)
- nor-Spd:
-
nor-spermidine (1,7-diamino-4-azaheptane)
- Spd:
-
spermidine (1,8-diamino-4-azaoctane)
- SSAT:
-
spermidine/spermine-N 1-acetyltransferase
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Original Russian Text © T.A. Keinanen, T. Hyvonen, J. Vepsalainen, L. Alhonen, A.R. Khomutov, J. Janne, 2014, published in Bioorganicheskaya Khimiya, 2014, Vol. 40, No. 2, pp. 170–177.
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Keinanen, T.A., Hyvonen, T., Vepsalainen, J. et al. Stable analogues of coenzyme-substrate complex of spermidine/spermine-N 1-acetyltransferase reaction. Synthesis and interaction with the enzyme. Russ J Bioorg Chem 40, 155–161 (2014). https://doi.org/10.1134/S1068162014020071
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DOI: https://doi.org/10.1134/S1068162014020071