Jump to main content
Jump to site search

Issue 2, 2017
Previous Article Next Article

Enhancement of the physicochemical properties of [Pt(dien)(nucleobase)]2+ for HIVNCp7 targeting

Author affiliations

Abstract

Physicochemical properties of coordination compounds can be exploited for molecular recognition of biomolecules. The inherent π–π stacking properties of [Pt(chelate)(N-donor)]2+ ([PtN4]) complexes were modulated by systematic variation of the chelate (diethylenetriamine and substituted derivatives) and N-donor (nucleobase or nucleoside) in the formally substitution-inert PtN4 coordination sphere. Approaches to target the HIV nucleocapsid protein HIVNCp7 are summarized building on (i) assessment of stacking interactions with simple tryptophan or tryptophan derivatives to (ii) the tryptophan-containing C-terminal zinc finger and (iii) to the full two-zinc finger peptide and its interactions with RNA and DNA. The xanthosine nucleoside was identified as having significantly enhanced stacking capability over guanosine. Correlation of the LUMO energies of the modified nucleobases with the DFT π-stacking energies shows that frontier orbital energies of the individual monomers can be used as a first estimate of the π-stacking strength to Trp. Cellular accumulation studies showed no significant correlation with lipophilicity of the compounds, but all compounds had very low cytotoxicity suggesting the potential for antiviral selectivity. The conceptual similarities between nucleobase alkylation and platination validates the design of formally substitution-inert coordination complexes as weak Lewis acid electrophiles for selective peptide targeting.

Graphical abstract: Enhancement of the physicochemical properties of [Pt(dien)(nucleobase)]2+ for HIVNCp7 targeting

Back to tab navigation

Supplementary files

Publication details

The article was received on 03 Aug 2016, accepted on 06 Oct 2016 and first published on 06 Oct 2016


Article type: Edge Article
DOI: 10.1039/C6SC03445D
Citation: Chem. Sci., 2017,8, 1269-1281
  • Open access: Creative Commons BY-NC license
  •   Request permissions

    Enhancement of the physicochemical properties of [Pt(dien)(nucleobase)]2+ for HIVNCp7 targeting

    S. D. Tsotsoros, P. B. Lutz, A. G. Daniel, E. J. Peterson, R. E. F. de Paiva, E. Rivera, Y. Qu, C. A. Bayse and N. P. Farrell, Chem. Sci., 2017, 8, 1269
    DOI: 10.1039/C6SC03445D

    This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material and it is not used for commercial purposes.

    Reproduced material should be attributed as follows:

    • For reproduction of material from NJC:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
    • For reproduction of material from PCCP:
      [Original citation] - Published by the PCCP Owner Societies.
    • For reproduction of material from PPS:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
    • For reproduction of material from all other RSC journals:
      [Original citation] - Published by The Royal Society of Chemistry.

    Information about reproducing material from RSC articles with different licences is available on our Permission Requests page.

Search articles by author

Spotlight

Advertisements