D‐ and L‐Mannose‐Containing glyco‐­Oligoamides Show Distinct Recognition Properties When Interacting with DNA

Abstract

Mannose glyco‐oligoamide β‐D‐Man‐Py‐γ‐Py‐Ind (β‐D‐Man, 1) and two new glyco‐oligoamides, β‐L‐Man‐Py‐γ‐Py‐Ind (β‐L‐Man, 2) and 6‐deoxy‐β‐D‐Man‐Py‐γ‐Py‐Ind (6‐deoxy‐β‐D‐Man, 3), have been designed and synthesized to investigate the role of hydrogen‐bonding cooperative donor centres of carbohydrates in their recognition by DNA. The free‐ and bound‐state geometries were studied, as were the affinities of the D and L enantiomers of the mannose glyco‐oligoamides (1 and 2) for DNA polymers [ct‐DNA and poly(dA‐dT)2]. TR‐NOESY and DF‐STD experiments for the diastereomeric complexes formed with DNA allow the asymmetric centres of the sugar residue that are close to the inner and outer regions of the DNA minor grooves to be distinguished. A C→N hairpin folding in β‐L‐Man derivative 2 was observed, with the α face of the sugar close to the indole ring. The C‐2 and C‐3 centres are orientated towards the inner region of the DNA minor groove. The affinity data for poly(dA‐dT)2 indicate that there is a chiral discrimination process, with β‐L‐Man derivative 2 being the best ligand. 6‐Deoxy‐β‐D‐Man derivative 3 forms the least stable complexes with DNA. Molecular dynamics simulations of β‐L‐Man derivative 2 in complex with a double‐strand dodecamer d(AT)12 are in agreement with the experimental NMR spectroscopic data. Thus, the cooperative donor centre 2‐OH in the L‐mannose enantiomer is a key contributor to the stability of the 2·poly(dA‐dT)2 complex.

Synthesis of rhamnosylated arginine glycopeptides and determination of the glycosidic linkage in bacterial elongation factor P

“…28 In this case β-selectivity was presumed to result from base-catalysed isomerization of the α-glycosylamine to the thermodynamically favoured equatorial (β) isomer. 27 Importantly, 2D NOESY NMR experiments of the two glycosyl isothiocyanates 3 and 4 confirmed the respective anomeric configurations (see ESI†). …”

“…26 Alternatively, treatment of the glycosyl acetate 5 with SnCl 4 and TMSN 3 provided glycosyl azide 7 . 27 This azide was reduced to the glycosylamine using H 2 ,Pd/C and, without purification, was treated with thiophosgene and CaCO 3 to afford the glycosyl isothiocyanate 4 as predominantly the β-isomer (α : β 1 : 9). 28 In this case β-selectivity was presumed to result from base-catalysed isomerization of the α-glycosylamine to the thermodynamically favoured equatorial (β) isomer.…”

On the importance of intramolecular hydrogen bond cooperativity in d‐glucose – an NMR and QTAIM approach

“…Although there is no corresponding NCI isosurface, interaction of the endocyclic oxygen with the anomeric OH group appears to be an important feature in both the free conformers and their pyridine complexes. Our conclusions agree neither with the assertion of Alonso et al (full cooperativity) nor with that of Silla et al (no cooperativity) but are consistent with work on 1,2‐diols, 1,3‐diols, 1,3‐amino alcohols and 1,3‐amido alcohols, where interaction with an electron‐accepting solvent enhances the intramolecular hydrogen bond strength . It remains to be seen whether one can design structures, possibly with more axial substituents, where cooperativity involves a third or fourth hydroxyl group.…”

Recent Advances in NMR Studies of Carbohydrates

“…The NMR spectrum assignment of the glyco-oligoamide/oligonucleotide 1:1 complex was based on the standard 2D NMR methodology employing TOCSY and NOESY experiments. TR-NOESY and STD experiments have been used to determine the bound conformation of the ligands in the presence two types of DNA by Blázquez-Sánchez et al [96].…”