Sodium glycocholate (NaGC) and taurocholate (NaTC) have been studied by means of X-ray and circular dichroism (CD) measurements, using bilirubin-lXa (BR) as probe molecule, together with potential-energy calculations. Helical models for the micellar aggregates of NaGC and NaTC were inferred from crystal structures solved by X-ray analysis. Since it is known that chiral molecules, micellar aggregates and macromolecules select preferentially or exclusively one of the two enantiomeric conformers of BR, CD spectra of BR in submicellar and micellar aqueous solutions of NaGC and NaTC were recorded as a function of pH and BR concentration in order to verify these helical models and the enantioselective ability of the bile salt monomers and micellar aggregates. Potential-energy calculations supported the CD experimental results and provided reasonable bile salt-BR interaction models. The behaviour of NaGC and NaTC is compared with that of sodium deoxycholate (NaDC), previously studied. The CD spectra of the bile salt-BR systems seem to allow characterisation of the typical structure of the bile salt micellar aggregates.

Potent and selective inhibitors of matrix metalloproteinases (MMPs), a family of zinc proteases that can degrade all the components of the extracellular matrix, could be useful for treatment of diseases such as cancer and arthritis. The most potent MMP inhibitors are based on hydroxamate as zinc-binding group (ZBG). alpha-Arylsulfonylamino phosphonates incorporate a particularly favorable combination of phosphonate as ZBG and arylsulfonylamino backbone so that their affinity exceptionally attains the nanomolar strength frequently observed for hydroxamate analogues. The detailed mode of binding of [1-(4'-methoxybiphenyl-4-sulfonylamino)-2-methylpropyl]phosphonate has been clarified by the crystal structures of the complexes that the R- and S-enantiomers respectively form with MMP-8. The reasons for the preferential MMP-8 inhibition by the R-phosphonate are underlined and the differences in the mode of binding of analogous alpha-arylsulfonylamino hydroxamates and carboxylates are discussed.

The structures of crystals of rubidium glycocholate (monoclinic) and rubidium taurocholate (monoclinic and tetragonal) were solved by X-ray diffraction analysis. These structures, together with those of the sodium salts formerly determined, were used to infer models for the corresponding micellar aggregates in aqueous solutions. The crystal packings of the sodium and rubidium salts were characterized by similar structural units. These were bilayers, 2 1 helices, distorted 21 helices, and units with a two-fold rotation axis. On the other hand, circular dichroism spectra of the sodium and rubidium salts with bilirubin-IXR in aqueous solution indicated the formation of very similar interaction complexes and micellar aggregates. This hypothesis was supported by quasi-elastic light scattering measurements carried out on aqueous micellar solutions as a function of the ionic strength, concentration, and temperature. Low values of the apparent hydrodynamic radius, corresponding to oligomers of small size, were obtained for all the salts. The micellar growth was practically independent of the concentration and temperature, within the range 20-60°C, at low ionic strength, and slightly increased upon increasing the ionic strength. We studied the rubidium salts in place of the sodium ones by extended X-ray absorption fine structure spectroscopy when their structures are similar. The measurements at the Rb + K-edge, previously accomplished on the crystal and the aqueous micellar solution of rubidium glycocholate, were in agreement with the model of the 21 helix and allowed us to discard the bilayer. Circular dichroism spectra, recorded as a function of the ionic strength, pointed out that bilirubin-IXR gives rise to a different enantioselective complexation with dihydroxy or trihydroxy salts. The different structure of the corresponding micellar aggregates was also supported by quasi-elastic light scattering measurements accomplished on dihydroxy and trihydroxy salts. The calculation of the hydrodynamic radius for the 2 1 helix, observed in the monoclinic crystal of sodium taurocholate, showed that there is a possible satisfactory agreement with the quasi-elastic light scattering data.

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