Recognition of the DNA minor groove by thiazotropsin analogues

Hasan Y. Alniss, Marie Virginie Salvia, Mykhailo Sadikov, Igor Golovchenko, Nahoum G. Anthony, Abedawn I. Khalaf, Simon P. MacKay, Colin J. Suckling, John A. Parkinson

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Solution-phase self-association characteristics and DNA molecular recognition properties are reported for three close analogues of minor groove binding ligands from the thiazotropsin class of lexitropsin molecules, which incorporate isopropyl thiazole as a lipophilic building block. Thiazotropsin B (AcImPyiPrThDp) shows similar self-assembly characteristics to thiazotropsin A (FoPyPyiPrThDp) although being engineered, by incorporation of imidazole in place of N-methyl pyrrole, to swap its DNA recognition target from 5´-ACTAGT-3´ to 5´-ACGCGT-3´. Replacement of the formamide head-group in thiazotropsin A by nicotinamide in AIK-18/51 results in a measureable difference in solution phase self-assembly character and substantially enhanced DNA association characteristics. The structures and associated thermodynamic parameters of self-assembled ligand aggregates and their complexes with respective DNA targets are considered in the context of cluster targeting of DNA by minor groove complexes.

Original languageEnglish
Pages (from-to)1978–1990
Number of pages13
JournalChembiochem
Volume15
Issue number13
Early online date16 Jul 2014
DOIs
Publication statusPublished - 5 Sep 2014

    Fingerprint

Keywords

  • thiazotropsins
  • DNA recognition
  • isothermal titration calorimetry
  • NMR
  • self-assembly
  • minor groove binder

Cite this

Alniss, H. Y., Salvia, M. V., Sadikov, M., Golovchenko, I., Anthony, N. G., Khalaf, A. I., ... Parkinson, J. A. (2014). Recognition of the DNA minor groove by thiazotropsin analogues. Chembiochem, 15(13), 1978–1990. https://doi.org/10.1002/cbic.201402202