Polymer-supported O-alkylisoureas: useful reagents for the O-alkylation of carboxylic acids

Polymer-supported O-alkylisoureas were prepared by reaction of an alcohol with a polymer-supported carbodiimide under copper(II) catalysis. These reagents were used to transform carboxylic acids into the corresponding methyl, benzyl, allyl, and p-nitrobenzyl esters in a highly chemoselective manner in high yields and in very high purity after simple resin filtration and solvent evaporation. The reactions could be carried out using both conventional or microwave heating, with reaction times as short as 3-5 min in the latter case, without compromising yield, purity, or chemoselectivity. Unfortunately, the corresponding solid-supported tert-butyl isoureas could not be prepared.     

A new tripodal receptor for molecular recognition of monosaccharides. A paradigm for assessing glycoside binding affinities and selectivities by 1H NMR spectroscopy

A new tripodal receptor for the recognition of monosaccharides is described. The prototypical host 1 features a 1,3,5-substituted 2,4,6-triethylbenzene scaffold bearing three convergent H-bonding units. The binding ability of the t-octyl derivative 1a toward a set of octylglycosides of biologically relevant monosaccharides, including Glc, Gal, Man, and GlcNAc, was investigated by 1H NMR in CDCl3. A protocol for the correct evaluation of binding affinities was established, which can be generally applied for the recognition of monosaccharides by 1H NMR spectroscopy. A three-constant equilibrium model, including 1:1 and 2:1 host-guest association and dimerization of the receptor, was ascertained for the interaction of 1a with all the investigated glycosides. An affinity index, which we defined median binding concentration BC50 in analogy to the IC50 parameter, intended to address the general issue of comparing dimensionally heterogeneous binding data, and a limiting BC0(50)quantity describing intrinsic binding affinities were developed for evaluating the results. BC0(50) values for 1a range from 1 to 6 mM, indicating an intrinsic binding affinity in the millimolar range and a selectivity factor of 5 toward the investigated glycosides. The treatment has been extended to include any generic host-guest system involved in single or multiple binding equilibria.     

Cloning and Characterization of Fructosamine-6-Kinase from Arthrobacter aurescens

Fructosamine-6-kinases (FN6Ks) that catalyze phosphorylation of glycated amino acids, i.e., fructosyl amino acids (FAs), have been shown as a potential recognition element for glycated protein detection. However, there are only two available FN6Ks: those from Escherichia coli which is specific for ε-fructosyl lysine (ε-FK) and Bacillus subtilis which recognizes both ε-FK and α-FA as substrates. In this study, we characterized an FN6K homologue isolated from Arthrobacter, some of whose species are reported to assimilate FA. The BLAST searches of Arthrobacter genomic database, using the bacterial FN6K primary structure information, revealed the presence of an FN6K homologue in Arthrobacter aurescens TC1 strain. Indeed, enzymatic assays confirmed that the putative FN6K from A. aurescens is an FN6K that is specific for ε-FK, although the primary sequence alignments showed similarity of A. aurescens FN6Ks with FN6Ks from B. subtilis and E. coli at the same level. In this study, we describe for the first time the presence of FN6K in Arthrobacter spp. and ε-FK-specific degradation pathway from Gram-positive bacteria, providing important information for the development of FA-recognizing molecules as well as for the FA assimilation system in bacteria.     

The Conformations of Amino Acids on a Gold(111) Surface

The interactions of amino acids with inorganic surfaces are of interest for biologists and biotechnologists alike. However, the structural determinants of peptide–surface interactions have remained elusive, but are important for a structural understanding of the interactions of biomolecules with gold surfaces. Molecular dynamics simulations are a tool to analyze structures of amino acids on surfaces. However, such an approach is challenging due to lacking parameterization for many surfaces and the polarizability of metal surfaces. Herein, we report DFT calculations of amino acid fragments in vacuo and molecular dynamics simulations of the interaction of all amino acids with a gold(111) surface in explicit solvent, using the recently introduced polarizable gold force field GolP. We describe preferred orientations of the amino acids on the metal surface. We find that all amino acids preferably interact with the gold surface at least partially with their backbone, underlining an unfolding propensity of gold surfaces.     

Insights into the Dynamics and Molecular Recognition Features of Glycopeptides by Protein Receptors: The 3D Solution Structure of Hevein Bound to the Trisaccharide Core of N‐Glycoproteins

Protein‐carbohydrate interactions are at the heart of a variety of essential molecular recognition events. Hevein, a model lectin related to the superantigen family, recognizes the trisaccharide core of N‐glycoproteins ( 1 ). A combined approach of NMR spectroscopy and molecular modeling has permitted us to demonstrate that an Asn‐linked Man(GlcNAc)₂ ( 2 ) is bound with even higher affinity than (GlcNAc)₃. The molecular recognition process entails conformational selection of only one of the possibilities existing for chitooligosaccharides. The deduced 3D structure of the hevein/ 2 complex permits the extension of polypeptide chains from the Asn moiety of 2 , as well as glycosylation at Man O‐3 and Man O‐6 of the terminal sugar. Given the ubiquity of the Man(GlcNAc)₂ core in all mammalian N‐glycoproteins, the basic recognition mode presented herein might be extended to a variety of systems with biomedical importance.     

Phosphido‐diphosphine pincer group 3 complexes as efficient initiators for lactide polymerization

New Group 3 metal complexes of the type [LM(CH₂SiMe₃)₂(THF)_n] supported by tridentate phosphido‐diphosphine ligands [(o‐C₆H₄PR₂) ₂ PH; L1‐H : R = iPr; L2‐H : R = Ph] have been synthesized by reaction of L1‐H and L2‐H with [M(CH₂SiMe₃)₃(THF)₂)] (M = Y and Sc). All the new complexes [(o‐C₆H₄PR₂) ₂ PM(CH₂SiMe₃)₂(THF)_n] [M = Y, R = iPr (1), R = Ph (2); M = Sc, R = iPr (3), R = Ph (4)] were studied as initiators for the ring opening polymerization of lactide. The yttrium complexes ( 1 and 2 ) exhibited high activity and good polymerization control, shown by the linear fits in the plot of number‐averaged molecular weight (M_n) versus the percentage conversion and versus the monomer/initiator ratio and by the low polydispersity index values. Interestingly, very good molar‐mass control was observed even when L ‐Lactide was polymerized in the absence of solvent at 130 °C. A good molar‐mass control but lower activities were observed in the polymerization reaction of lactide promoted by the analogous scandium complexes 3 and 4 . © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 1374–1382, 2010     

Synthesis of polymers containing regularly distributed tetrathia‐[7]‐elicene units along the backbone

A tetrathia‐[7]‐helicene bearing in the 2 and 13 positions cyanovinyl groups was used as comonomer in the Michael‐type polyaddition reaction with N,N′‐bis(β‐mercaptoethyl)piperazine. This led to a new polymer bearing tetrathia‐[7]‐helicene units regularly distributed along the polymer backbone, which may be regarded as the first example of a new family of potentially useful nonlinear optical materials. All products were structurally characterized by ¹H and ¹³C NMR spectroscopy. Differential scanning calorimetry characterizations revealed the presence, in both monomeric and polymeric helicenes, of glass‐transition like temperatures, associated to some conformational variation of the helicene units. The optical properties, the film formation and the morphology of the polymer‐containing tetratia‐[7]‐helicenes were also investigated. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010