Hydrophobic vs Coulombic Interactions in the Binding of Steroidal Polyamines to DNA

Abstract

Seven new steroidal polyamines derived from bile acids, either lithocholic or deoxycholic acid, have been studied as DNA-binding agents using four complimentary methods: an ethidium displacement assay, observed changes in the thermal denaturation of poly[d(AT)], effects on hyperchromicity of DNA, and circular dichroism. In addition, modelling studies were conducted to examine the electrostatic surface potential of the polycations. The results point to a key role for a large hydrophobic surface area on the steroid in addition to the Coulombic attraction by ammonium and guanidinium groups on the steroid interacting with the polyphosphate backbone.

Kanamycin A‐Derived Cationic Lipids as Vectors for Gene Transfection

“…On the other hand, both the strong basicities of the guanidinium groups (p K a around 13.645) and their planar structures (which allow the formation of chelating hydrogen bonds) are likely to reinforce the interactions between the headgroup and the DNA 27. 46 Accordingly, recent studies showed that the binding of guanidinium and ammonium groups to phosphate could be characterised by different thermodynamic profiles 47. 48…”

Kanamycin A‐Derived Cationic Lipids as Vectors for Gene Transfection

“…On the other hand, both the strong basicities of the guanidinium groups (p K a around 13.645) and their planar structures (which allow the formation of chelating hydrogen bonds) are likely to reinforce the interactions between the headgroup and the DNA 27. 46 Accordingly, recent studies showed that the binding of guanidinium and ammonium groups to phosphate could be characterised by different thermodynamic profiles 47. 48…”

Use of Bile Acids in Pharmacological and Supramolecular Applications

“…Bile acid polyamine conjugates are potential agents in gene therapy28 because of the Coulombic attraction between the polyamine moieties and the polyphosphate backbone of deoxyribonucleic acid 29. Burrows et al29−31 have published several papers concerning the synthesis of deoxycholic and lithocholic acid‐based polyamines and studies of their binding affinities with DNA.…”

“…Bile acid polyamine conjugates are potential agents in gene therapy28 because of the Coulombic attraction between the polyamine moieties and the polyphosphate backbone of deoxyribonucleic acid 29. Burrows et al29−31 have published several papers concerning the synthesis of deoxycholic and lithocholic acid‐based polyamines and studies of their binding affinities with DNA. Blagbrough and co‐workers28,32,33 have investigated the effects of changes in the stereochemistry and position of the alcohol functional groups on the cholane ring system of bile acids on the relative binding affinities for CT (calf thymus) DNA.…”

Solution Structure of a Steroid−DNA Complex with Cholic Acid Residues Sealing the Termini of a Watson−Crick Duplex

“…Instead, they are known to induce their effect on genomic DNA through nuclear receptors ( − ). Some reports on direct molecular interactions between steroids and DNA exist, but most of these are on steroidal amines ( − ), not hormones (), sterols, or bile acids without cationic groups. When steroid derivatives were appended to oligonucleotides to be employed for biotechnological or biomedical applications ( − ), it was steroid−steroid interactions ( , ), or interactions with receptors ( , ) or membranes ( − ), that were envisioned, and not steroid−DNA interactions.…”

Kanamycin A‐Derived Cationic Lipids as Vectors for Gene Transfection

“…On the other hand, both the strong basicities of the guanidinium groups (p K a around 13.645) and their planar structures (which allow the formation of chelating hydrogen bonds) are likely to reinforce the interactions between the headgroup and the DNA 27. 46 Accordingly, recent studies showed that the binding of guanidinium and ammonium groups to phosphate could be characterised by different thermodynamic profiles 47. 48…”

Use of Bile Acids in Pharmacological and Supramolecular Applications

“…Bile acid polyamine conjugates are potential agents in gene therapy28 because of the Coulombic attraction between the polyamine moieties and the polyphosphate backbone of deoxyribonucleic acid 29. Burrows et al29−31 have published several papers concerning the synthesis of deoxycholic and lithocholic acid‐based polyamines and studies of their binding affinities with DNA.…”

“…Bile acid polyamine conjugates are potential agents in gene therapy28 because of the Coulombic attraction between the polyamine moieties and the polyphosphate backbone of deoxyribonucleic acid 29. Burrows et al29−31 have published several papers concerning the synthesis of deoxycholic and lithocholic acid‐based polyamines and studies of their binding affinities with DNA. Blagbrough and co‐workers28,32,33 have investigated the effects of changes in the stereochemistry and position of the alcohol functional groups on the cholane ring system of bile acids on the relative binding affinities for CT (calf thymus) DNA.…”

Solution Structure of a Steroid−DNA Complex with Cholic Acid Residues Sealing the Termini of a Watson−Crick Duplex

“…Instead, they are known to induce their effect on genomic DNA through nuclear receptors ( − ). Some reports on direct molecular interactions between steroids and DNA exist, but most of these are on steroidal amines ( − ), not hormones (), sterols, or bile acids without cationic groups. When steroid derivatives were appended to oligonucleotides to be employed for biotechnological or biomedical applications ( − ), it was steroid−steroid interactions ( , ), or interactions with receptors ( , ) or membranes ( − ), that were envisioned, and not steroid−DNA interactions.…”

Kanamycin A‐Derived Cationic Lipids as Vectors for Gene Transfection

“…On the other hand, both the strong basicities of the guanidinium groups (p K a around 13.645) and their planar structures (which allow the formation of chelating hydrogen bonds) are likely to reinforce the interactions between the headgroup and the DNA 27. 46 Accordingly, recent studies showed that the binding of guanidinium and ammonium groups to phosphate could be characterised by different thermodynamic profiles 47. 48…”

Use of Bile Acids in Pharmacological and Supramolecular Applications

“…Bile acid polyamine conjugates are potential agents in gene therapy28 because of the Coulombic attraction between the polyamine moieties and the polyphosphate backbone of deoxyribonucleic acid 29. Burrows et al29−31 have published several papers concerning the synthesis of deoxycholic and lithocholic acid‐based polyamines and studies of their binding affinities with DNA.…”

“…Bile acid polyamine conjugates are potential agents in gene therapy28 because of the Coulombic attraction between the polyamine moieties and the polyphosphate backbone of deoxyribonucleic acid 29. Burrows et al29−31 have published several papers concerning the synthesis of deoxycholic and lithocholic acid‐based polyamines and studies of their binding affinities with DNA. Blagbrough and co‐workers28,32,33 have investigated the effects of changes in the stereochemistry and position of the alcohol functional groups on the cholane ring system of bile acids on the relative binding affinities for CT (calf thymus) DNA.…”

Solution Structure of a Steroid−DNA Complex with Cholic Acid Residues Sealing the Termini of a Watson−Crick Duplex

“…Instead, they are known to induce their effect on genomic DNA through nuclear receptors ( − ). Some reports on direct molecular interactions between steroids and DNA exist, but most of these are on steroidal amines ( − ), not hormones (), sterols, or bile acids without cationic groups. When steroid derivatives were appended to oligonucleotides to be employed for biotechnological or biomedical applications ( − ), it was steroid−steroid interactions ( , ), or interactions with receptors ( , ) or membranes ( − ), that were envisioned, and not steroid−DNA interactions.…”