Binding of Nucleotides and Nucleosides to Per(6‐guanidino‐6‐deoxy)cyclodextrins in Solution

Abstract

Keywords: Cyclodextrins / NMR spectroscopy / Nucleotides / Electrostatic interactions / Host-guest systems / Ribose pucker / MultivalencyThe binding of α-, β-, and γ-per(6-guanidino-6-deoxy)cyclodextrins (ag, bg, and gg, respectively) with nucleotides (5Ј-dAMP, 5Ј-AMP, and 5Ј-dCMP) and nucleosides (2Ј-dA and 2Ј-dC) was studied with NMR spectroscopy in aqueous solution. Nucleotides formed strong complexes with bg and gg (not ag) through ditopic binding. Multiple Coulombic attractive forces between the guanidino groups and the single phosphate group of the nucleotides drove inclusion of the entire ribose ring into the cavity, in both deoxy-and ribonucleotides, whereas the base moiety was only partially included. In contrast, no interaction was observed between guanidino cyclodextrins and nucleosides. The prevailing stoichiometries in all nucleotide/bg and nucleotide/gg com-

Positively charged cyclodextrins as effective molecular transporters of active phosphorylated forms of gemcitabine into cancer cells

“…insertion of a guest from the wide CD opening in order to enhance attractive Coulombic forces resulting in stronger binding, partial or total inclusion of the difluororibose moiety as well as part of the nucleobase. The strong stabilizing effect of the phosphate groups leading to unexpected inclusion of the ribose unit in the hydrophobic CD cavity has been demonstrated previously when studying the interaction of nucleotides with 3 15 and also with other amino and guanidino CDs 21 – 23 . The presence of the two fluorine atoms is expected to increase the hydrophobicity of the ribose moiety and enhance complexation, compared to deoxycytidine or cytidine nucleotides with 3 15 .…”

“…1b ) have been shown to strongly bind aromatic phosphorylated guests through both cavity inclusion and ionic interactions 14 . Similar binding has been observed for nucleotides 15 where the deoxyribose moiety was shown to enter the cavity of per(6-guanidino-6-deoxy)-α, -β ( 3 ) and -γCD in a process driven by the phosphate-guanidino group interactions. On the other hand, the same hosts were unable to bind nucleosides, confirming the importance of electrostatic stabilization for the molecular encapsulation.…”

“…Inclusion complex formation could account for such effects because restriction, for example, of the difluororibose moiety in a cavity could affect its conformational freedom i.e. the syn - anti conformational exchange or even the rate of C3′-endo (N)/C3′-exo (S) puckering of the ribose, as observed previously for deoxyadenosine monophosphate with 3 15 . Extensive broadening was also detected with dFdCMP/ 3 and dFdCTP/ 3 most likely as the result of external guanidino–phosphate interactions.…”

Modified Cyclodextrins with Pendant Cationic and Anionic Moieties as Hosts for Highly Stable Inclusion Complexes and Molecular Recognition

“…Binding of per(6-guanidino-6-deoxy)-cyclodextrins 6a -6c with nucleotides (5'-dAMP, 5'-AMP, and 5'-dCMP) and nucleosides (2'-dA and 2'-dC) was studied with NMR spectroscopy in aqueous solution [77]. Nucleotides formed strong complexes with 6b and 6c (not 6a) whilst no interaction was observed between guanidino cyclodextrins and nucleosides.…”

Cooperative heterodimer formation between per-guadinylated and carboxylated or phosphorylated cyclodextrins in DMSO and DMSO–water studied by NMR spectroscopy and microcalorimetry

“…The presence of guanidino groups on the primary (narrow) side of CDs (Scheme 1a), i.e. in hexakis-, heptakis-and octakis(6-guanidino-6-deoxy)-CDs (10), endows them with unique properties: (i) they include anionic guests strongly and preferentially in their cavity (10), (ii) consequently they can efficiently capture nucleotides (11), (iii) they strongly bind DNA which in their presence is packed into nanoparticles (10). The ability to include nucleotides has been previously demonstrated with amino-substituted CDs (12)(13)(14)(15)(16) as well as mono-or bis-guanidino-CDs (15,17) the latter presenting an enthalpic advantage over the amino CDs in stabilization of binding.…”