Sulfur Groups Improve the Performance of Triazole- and Triazolium-Based Interaction Units in Anion Binding.

An NMR comparative study of 1,2,3-triazole and triazolium anion recognition units containing sulfoxide, sulfone, and sulfoximine groups at C unveils an enhancement in binding ability up to ≈1 kcal/mol in acetone-d correlated with a theoretical increase of H acidity. DFT calculations provide insight into binding modes in line with experimental data for these receptors.

Cooperative hydrogen bonding in glyco-oligoamides: DNA minor groove binders in aqueous media.

A strategy to create cooperative hydrogen-bonding centers by using strong and directional intramolecular hydrogen-bonding motifs that can survive in aqueous media is presented. In particular, glyco-oligoamides, a family of DNA minor groove binders, with cooperative and non-cooperative hydrogen-bonding donor centers in the carbohydrate residues have been designed, synthesized, and studied by means of NMR spectroscopy and molecular modeling methods. Indeed, two different sugar moieties, namely, β-D-Man-Py-γ-Py-Ind (1; Ind=indole, Man=mannose, Py=pyrrole) and β-D-Tal-Py-γ-Py-Ind (2; Tal=talose), were chosen according to our design.

Sugar-oligoamides: synthesis of DNA minor groove binders.

Sugar-oligoamides have been designed and synthesized as structurally simple carbohydrate-based ligands to study carbohydrate-minor groove DNA interactions. Here we report an efficient solution-phase synthetic strategy to obtain two broad families of sugar-oligoamides. The first type, structure vector A (-Py[Me]-γ-Py-Ind), has a methyl group present as a substituent on the nitrogen of pyrrole B, connected to the C terminal of the oligoamide fragment.

Carbohydrate recognition at the minor-groove of the self-complementary duplex d(CGCGAATTCGCG)2 by a synthetic glyco-oligoamide.

The structure of a neutral glyco-conjugate β-Gal-Py-γ-Py-Ind (1), designed as a probe for analyzing sugar-DNA interactions, when bound to a self-complementary oligonucleotide duplex d(CGCG AATT CGCG)(2) has been deduced by employing (1)H NMR techniques. Analysis of the formed 1:1 complex demonstrated that the glycol ligand is bound in a hairpin-like conformation in which both pyrrole amino acid moieties are stacked, whereas the indole and the sugar residues are spatially close. The binding site is defined by the minor groove formed by the -AATT- stretch.

A synthetic lectin for O-linked beta-N-acetylglucosamine.

Changing employment: Receptor 1 binds beta-N-acetylglucosaminyl (beta-GlcNAc) up to 100 times more strongly than it does glucose. This synthetic lectin shows affinities similar to wheat germ agglutinin (WGA), a natural lectin used to bind GlcNAc. Remarkably, 1 is more selective than WGA.

Sugar-oligoamides: bound-state conformation and DNA minor-groove-binding description by TR-NOESY and differential-frequency saturation-transfer-difference experiments.

Selective-frequency saturation-transfer-difference (STD) spectra allow the description of complexes established between minor-groove binders and long tracts of calf thymus DNA (ct-DNA). Two sets of experiments with selective saturation of either the H1' or H4'/H5'/H5'' proton NMR regions of deoxyribose allow the description of the ligand residues close to the inner (H1') and outer regions (H4'/H5'/H5'') of the minor groove of double-helical DNA. A series of complexes of sugar-oligoamides (2-6) with ct-DNA have been studied by both TR-NOESY and STD experiments.

Carbohydrate-based DNA ligands: sugar-oligoamides as a tool to study carbohydrate-nucleic acid interactions.

Sugar-oligoamides have been designed and synthesized as structurally simple carbohydrate-based ligands to study carbohydrate-DNA interactions. The general design of the ligands 1-3 has been done as to favor the bound conformation of Distamycin-type gamma-linked covalent dimers which is a hairpin conformation. Indeed, NMR analysis of the sugar-oligoamides in the free state has indicated the presence of a percentage of a hairpin conformation in aqueous solution.

Hydrogen-bonding cooperativity: using an intramolecular hydrogen bond to design a carbohydrate derivative with a cooperative hydrogen-bond donor centre.

Neighbouring groups can be strategically located to polarise HO.OH intramolecular hydrogen bonds in an intended direction. A group with a unique hydrogen-bond donor or acceptor character, located at hydrogen-bonding distance to a particular OH group, has been used to initiate the hydrogen-bond network and to polarise a HO.

A prototype calix[4]arene-based receptor for carbohydrate recognition containing peptide and phosphate binding groups.

A novel class of macrobicyclic receptors for carbohydrate recognition based on upper rim, peptide-bridged calix[4]arenes has been designed and synthesized. Receptor 12, in which a charged phosphate group cooperates with peptide hydrogen-bonding donor and acceptor groups in the binding process, is the most efficient and selective in the complexation of simple carbohydrate derivatives. The selectivity observed is toward beta-glucoside 13a, which is better bound (DeltaG degrees = 19.

Experimental evidence for the existence of non-exo-anomeric conformations in branched oligosaccharides: NMR analysis of the structure and dynamics of aminoglycosides of the neomycin family.

It is commonly known that the exo-anomeric effect is a major factor governing the conformational behavior of naturally occurring oligosaccharides. Conformational flexibility in these molecules mainly concerns the aglycon psi angle since phi is restricted by this stereo-electronic effect. In fact, to the best of our knowledge no case of a natural glycoside adopting a non-exo-anomeric conformation in solution has yet been reported.

Experimental evidence for the existence of non-exo-anomeric conformations in branched oligosaccharides: the neomycin-B case.

For the first time in natural O-glycosides, a large amount of non-exo-anomeric conformation is experimentally detected, in solution.

The relevance of carbohydrate hydrogen-bonding cooperativity effects: a cooperative 1,2-trans-diaxial diol and amido alcohol hydrogen-bonding array as an efficient carbohydrate-phosphate binding motif in nonpolar media.

Carbohydrates with suitably positioned intramolecularly hydrogen-bonded hydroxyl and amide groups have the potential to act as efficient bidentate phosphate binders by taking advantage of sigma- and/or ,sigma,pi-H-bonding cooperativity in nonpolar solvents. Donor-donor 1,2-trans-diaxial amido alcohol (1) and diol (3), in which one of the donor centres is cooperative, are very efficient carbohydrate-phosphate binding motifs. We have proven and quantified the key role of hydrogen-bonding centres indirectly involved in complexation, which serve to generate an intramolecular H-bond (six-membered cis H-bond) in 1 and 3.