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Novel hydroxylamine-containing analogues of 1-guanidino-7-aminoheptane (GC7), an effective inhibitor of deoxyhypusine synthase

Abstract

Earlier unknown hydroxylamine-containing analogues of 1-guanidino-7-aminohepane (GC7) containing the free aminooxy group (1-aminooxy-6-guanidinohexane), bis-guanyl derivatives of 1-aminooxy-6-aminohexane, and 1-aminooxy-5-aminopentane, and mono-guanidinooxy analogue (1-guanidinooxy-6-aminohexane) were synthesized in high overall yields from commercially available 5-(Boc-amino)1-pentanol and 6-(Boc-amino)-1-hexanol. It was demonstrated that 1,3-di-Boc-2-(trifluoromethylsulfonyl)guanidine is able to specifically amidinate the amino group in the presence of the free aminooxy group. The application of newly synthesized GC7 analogues for the investigation of the peculiarities of their interaction with the active site of deoxyhypusine synthase was discussed.

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Abbreviations

DHS:

deoxyhypusine synthase

GC7:

1-guanidino-7-aminoheptane

Ms:

methanesulfonyl

Spd:

spermidine (1,8-diamino-4-azaoctane)

1-MeSpd:

1,8-diamino-5-azanonane

Spm:

spermine (1,12-diamine-4,8-diazadodecane)

2MeSpd:

1,8-diamino-2-methyl-4-azaoctane

3-MeSpd:

1,8diamino-3-methyl-4-azaoctane

triflate:

trifluoromethyl sulfonyl.

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Correspondence to A. R. Khomutov.

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Original Russian Text © M.A. Khomutov, A.R. Simonian, J. Weisell, J. Vepsalainen, S.N. Kochetkov, A.R. Khomutov, 2016, published in Bioorganicheskaya Khimiya, 2016, Vol. 42, No. 4, pp. 460–468.

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Khomutov, M.A., Simonian, A.R., Weisell, J. et al. Novel hydroxylamine-containing analogues of 1-guanidino-7-aminoheptane (GC7), an effective inhibitor of deoxyhypusine synthase. Russ J Bioorg Chem 42, 415–422 (2016). https://doi.org/10.1134/S1068162016040099

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  • DOI: https://doi.org/10.1134/S1068162016040099

Keywords

  • polyamines
  • inhibitors
  • GC7 analogues
  • O-substituted hydroxylamines
  • alkoxyguanidines
  • deoxyhypusine synthase