Alpha-O-linked glycopeptide mimetics: synthesis, conformation analysis, and interactions with viscumin, a galactoside-binding model lectin.

Efficient cycloaddition of a silylidene-protected galactal with a suitable heterodiene yielded the basis for a facile diastereoselective route to a glycopeptide-mimetic scaffold. Its carbohydrate part was further extended by beta1-3-linked galactosylation. The pyranose rings retain their (4)C(1) chair conformation, as shown by molecular modeling and NMR spectroscopy, and the typical exo-anomeric geometry was observed for the disaccharide.

Ion-pair binding: is binding both binding better?

It is often tempting to explain chemical phenomena on the basis of intuitive principles, but this practice can frequently lead to biased analysis of data and incorrect conclusions. One such intuitive principle is brought into play in the binding of salts by synthetic receptors. Following the heuristic concept that "binding both is binding better", it is widely believed that ditopic receptors capable of binding both ionic partners of a salt are more effective than monotopic receptors because of a cooperative effect.

Synthesis, conformation, and biological characterization of a sugar derivative of morphine that is a potent, long-lasting, and nontolerant antinociceptive.

A synthetic mannoside derivative, namely, 6-morphinyl-alpha-D-mannopyranoside, shows a naloxone-reversible antinociception that is 100-fold more potent and twice as long lasting compared to morphine when administered intraperitoneally to rats in paw pressure and tail flick tests. The compound does not produce tolerance and binds to rat mu opioid receptors with twice the affinity of morphine. NMR studies suggest that differences of activity between the derivative and its parent compound M6G might be related to their differing molecular dynamic behavior.

Synthesis and conformational analysis of (alpha-D-galactosyl)phenylmethane and alpha-,beta-difluoromethane analogues: interactions with the plant lectin viscumin.

(Alpha-D-galactosyl)phenylmethane (1), (alpha- and beta-D-galactosyl)(difluoro)phenylmethane (2 and 3) have been prepared and their conformations in solution were described by using a combination of force-field calculations and NMR spectroscopic studies. Galactoside 1 adopts a (4)C(1) chair conformation and an exo anomeric orientation, as is the case for natural alpha-galactosides. The X-ray crystal structure of its difluoromethylene derivative 2 similarly shows a (4)C(1) chair conformation.

Binding of ionic species: a general approach to measuring binding constants and assessing affinities.

Bound together: The association of receptors with ionic species cannot be assimilated to the binding of neutral guests. When dealing with salts, both ion pairing and binding to the free and the ion-paired ionic guest determine the actual association pattern (see figure). The general issue of measuring association constants and assessing affinities for ions is addressed and validated in two cases of anion binding.

A new scaffold for the stereoselective synthesis of alpha-O-linked glycopeptide mimetics.

alpha-O-Linked glycohomoglutamates are obtained as diastereomerically pure compounds by chemo-, regio-, and stereoselective cycloadditions between glycals and aspartic acid derivatives. The latter constitute orthogonally functionalized scaffolds for glycopeptide mimetics.