Conformational properties of sugars

The glycosidase-inhibitory properties of sugar-shaped cyclic thioureas were first, explored by Lehmann and co-workers,414 who obtained the hexa-hydropyrimidine-2-thione glucomimetic 271 by thiocarbonylation of the diamine precursor 270. Compound 271 was a very weak inhibitor of sweet-almond /3-glucosidasc, and this was ascribed to the lack of the OH group at the homologous position of C-3 in n-glucopyranosidcs. Moreover, an unexpected preference for the irons-diaxial conformation in deuterium oxide solution. was observed (Scheme 73). 

The first such approach to the interpretation of optical rotation in terms of the conformational properties of carbohydrates was made by Whifien in 1956. He proposed that the observed rotation of an optically active molecule can be regarded as an algebraic summation of partial rotatory contributions of various conformational elements of asymmetry. For these contributions, empirical values were determined that allowed estimation of the net rotations of various cyclic sugars and cyclitols with fair accuracy. A more extensive treatment was presented by Brewster,and it was applied to a wide range of optically active, acyclic and cyclic compounds. The best correlations between the calculated and the experimental values were obtained with compounds that do not absorb in the near-ultraviolet and have predictable, fixed conformations, or for which the conformational populations can be reliably estimated. In the carbohydrate field, the calculations are quite simple for the poly-hydroxycyclohexanes, - and differences between the calculated and observed values for the rotation have been interpreted in terms of conformational equilibria. Similar comparisons have been made for the methyl D-aldopyranosides, although the lack of precision in the correlation does not allow a detailed treatment in terms of conformational populations. 

SDEL was also used to study the coil-helix transition of an alanine-rich peptide [68], the conformational transition of sugar puckering in deoxyadenosine [69], polymerase P [70], and the B-Z DNA transition [71,72]. The coil to helix study [68] demonstrated several properties of SDEL trajectories, like the filtering of high frequency modes and the preservation of thermodynamic properties from slow degrees of freedom when the trajectory resolution is decreased. 

Later MD studies on DNA triplexes were often devoted to the stability and the H-bond pattern of the base triads, to the conformational properties of the sugar-phosphate backbone, to the effect of modified nucleotides and to the hydration pattern. Modified nucleotides include structures derived from 2-aminopyridine and 8-aminoguanine a triplex with the phosphodiester linkage in two strands replaced by S-methylthiourea linkers, 2 -aminoethoxy-substituted riboses and a -CH2-lengthening of the intemucleotide linkage. ... 

Only some aspects of the solvent perturbation on the conformational properties of carbohydrate polymers have been covered in this chapter. One of the maj or concerns has been to develop a description of these solvent effects starting with the complex conformational equilibria of simple sugars. In fact, only recently it has been fully appreciated the quantitative relationship between conformational population and physical properties, e.g. optical rotation. 

The observed slopes ( i - 1) Indicate that there Is a 1 1 correspondence between the sugar ring and backbone conformational properties of nucleosides and nucleotides, le, m V 1 In equation (1). This observation Is a prerequisite of the existence In solution of a highly stable nucleotidyl conformational state. 

Relationship between backbone C 5 )-C 4 ) bond ( +) and sugar ring N (%) conformational properties of pyrimidine (Figure 4) and purine (Figure 5) nucleosides and 5 -nucleotides. Ihe correlations between Z and (slope - 1) observed for nucleosides (which Includes results for 3 -nucleotides... 

This model also shows that the conformational properties of the sugar ring (summarised by Ip ] and the exocycllc C (3 ) -O (3 ) bond (<]) ) are directly related which Is a necessary precondition for observation of a persistent conformation for nucleotides In solution. 

Figure 8 Multivalency in carbohydrate-protein interactions can occur once a lectin with clustered sugar-binding sites and a multivalent saccharide are involved. Depending on the structural and conformational properties of a saccharide, the carbohydrate-protein interaction can be monovalent or multivalent (here divalent). Moreover, binding can occur either intra- or intermolec-ularly.

A symposium report has been published on the conformational properties of deo genated sugars, with emphasis on furanose derivatives. A review with 18 references is concerned with certain stereochemical problems associated with small carbohydrate molecules and aims to show how the combination of experimental n.m.r. studies and theoretical computer simulation can be brought to bear on their resolution. In connection with the total synthesis of palytoxin, a review has been written covering the conformational anal is of O-and C-disaccharides and presents a useful mode (diamond lattice diagrams) for predicting the solution conformations of these compounds. A further review deals with C-n.m.r. studies, especially by use of relaxation probes, of the interaction between metal ions and carbohydrates. ... 

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