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Luliberin analogues containing the nuclear localization sequence of the SV-40 virus T-antigen

Abstract

With the goal of improving the efficacy of anticancer drugs due to the directed delivery to intracellular targets, a set of luliberin analogues containing the nuclear localization signal (NLS) of the SV-40 virus large T-antigen has been synthesized. The NLS was attached to the parent molecule via the D-lysine ɛ-amino group introduced into position 1 or 6 of the peptide sequence using the orthogonal protection strategy. Biological tests demonstrated that this modification supported in vitro a significant increase in the cytotoxic activity of luliberin analogues containing palmitoyl residues. The influence of the studied peptides on tumor cells was not associated with the distortion of the membrane integrity, which was confirmed by experiments with normal fibroblasts used as a control.

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Abbreviations

ATCC:

American typical culture collection

Bzl(Cl2):

2,6-dichlorobenzyl

DMEM:

Dulbecco’s modified Eagle medium

GnRH:

luliberin

Mts:

mesitylenesulfonyl

NLS:

nuclear localization signal

Pam:

palmitoyl

PBS:

phosphate buffer solution

TFMSA:

trifluoromethanesulfonic acid

TEA:

triethylamine

Trt:

triphenylmethyl

Z(Cl):

2-chloromethyloxycarbonyl

RCCC:

Russian cell culture collection

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Correspondence to S. V. Burov.

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Original Russian Text © S.V. Burov, T.V. Yablokova, M.Yu. Dorosh, E.V. Krivizyuk, A.M. Efremov, S.V. Orlov, 2010, published in Bioorganicheskaya Khimiya, 2010, Vol. 36, No. 5, pp. 630–637.

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Burov, S.V., Yablokova, T.V., Dorosh, M.Y. et al. Luliberin analogues containing the nuclear localization sequence of the SV-40 virus T-antigen. Russ J Bioorg Chem 36, 581–588 (2010). https://doi.org/10.1134/S1068162010050055

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  • DOI: https://doi.org/10.1134/S1068162010050055

Key words

  • anticancer activity
  • luliberin
  • nuclear localization signal
  • palmitic acid