Understanding the DNA binding of novel non-symmetrical guanidinium/2-aminoimidazolinium derivatives

Abstract

Biophysical studies have been carried out on a family of asymmetric guanidinium-based diaromatic derivatives to assess their potential as DNA minor groove binding agents. To experimentally assess the binding of these compounds to DNA, solution phase biophysical studies have been performed. Thus, surface plasmon resonance, UV-visible spectroscopy and circular and linear dichroism have been utilized to evaluate binding constants, stoichiometry and mode of binding. In addition, the thermodynamics of the binding process have been determined by using isothermal titration calorimetry. These results show significant DNA binding affinity that correlates with the expected 1 : 1 binding ratio usually observed for minor groove binders. Moreover, a simple computational approach has been devised to assess the potential as DNA binders of this family of compounds.

On the protonated state of amidinium-like diaromatic derivatives: X-ray and UV studies

“…A weaker change occurs at around 290 nm between pH 9.2 and 13 corresponding to the formation of the neutral species. The corresponding pK a values obtained were 5.0 and 11.8 for the -NH 3 ? and guanidinium deprotonations, respectively (Table 3).…”

“…Compounds containing amidine-like groups (guanidines, 2-aminoimidazolines, isoureas) have shown to be active in different biological systems from binding to DNA [1][2][3] to inhibiting adrenergic receptors in the brain [4][5][6]. The protonation state of these amidine-like groups at physiological level plays a fundamental role in the interactions established with the target (hydrogen bonds, ionic contacts) and for this reason, information about this protonation state is crucial for the design of new biologically active derivatives.…”

Antiprotozoal activity and DNA binding of N-substituted N-phenylbenzamide and 1,3-diphenylurea bisguanidines

“…Since N-phenylbenzamide and 1,3-diphenylurea guanidine and imidazoline derivatives are strong DNA minor groove binders [11,[26][27][28], we were interested in quantitatively evaluating the binding affinity of the new compounds with DNA. Binding to DNA and resultant inhibition of transcription and activity of other DNA-dependent enzymes is thought to contribute to the antiprotozoal activity of dicationic compounds [29].…”

Cleavage of 2‐(Arylamino)‐4,6‐dimethoxypyrimidines To Yield Arylguanidines

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] …”