Ligand-aggregation

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Thiazotropsin Aggregation and Its Relationship to Molecular Recognition in the DNA Minor Groove

Journal Title, Volume, Page: 
Biophysical Chemistry Volume 179, September 2013, Pages 1–11
Year of Publication: 
2013
Authors: 
Marie-Virginie Salvia
WestCHEM Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, United Kingdom
Fiona Addison
WestCHEM Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, United Kingdom
Hasan Y. Alniss
Strathclyde Institute of Pharmaceutical and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, United Kingdom
Current Affiliation: 
Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
Niklaas J. Buurma
School of Chemistry, University of Cardiff, Main Building, Park Place, Cardiff CF10 3AT, United Kingdom
Abedawn I. Khalaf
WestCHEM Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, United Kingdom
Simon P. Mackay
Strathclyde Institute of Pharmaceutical and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, United Kingdom
Nahoum G. Anthony
Strathclyde Institute of Pharmaceutical and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, United Kingdom
Colin J. Suckling
WestCHEM Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, United Kingdom
Maxim P. Evstigneev
Department of Physics, Sevastopol National Technical University, Sevastopol 99053, Crimea, Ukraine
Adrián Hernandez Santiago
Department of Physics and Mathematics, Faculty of Chemistry, Autonomous University of Puebla, Puebla CP 72570, Mexico
Roger D. Waigh
Strathclyde Institute of Pharmaceutical and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, United Kingdom
John A. Parkinson
WestCHEM Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, United Kingdom
Preferred Abstract (Original): 

Aggregated states have been alluded to for many DNA minor groove binders but details of the molecule-on-molecule relationship have either been under-reported or ignored. Here we report our findings from ITC and NMR measurements carried out with AIK-18/51, a compound representative of the thiazotropsin class of DNA minor groove binders. The free aqueous form of AIK-18/51 is compared with that found in its complex with cognate DNA duplex d(CGACTAGTCG)2. Molecular self-association of AIK-18/51 is consistent with anti-parallel, face-to-face dimer formation, the building block on which the molecule aggregates. This underlying structure is closely allied to the form found in the ligand's DNA complex. NMR chemical shift and diffusion measurements yield a self-association constant Kass = (61 ± 19) × 103 M− 1 for AIK-18/51 that fits with a stepwise self-assembly model and is consistent with ITC data. The deconstructed energetics of this assembly process are reported with respect to a design strategy for ligand/DNA recognition.

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