Chirality-driven folding of short ß-lactam pseudopeptides.

Novel enantiopure pseudopeptide models containing a central -(ß-lactam)-(Aa)- scaffold characterized by the combined presence of an α-alkyl-α-amino-ß-lactam (i+1) residue and a α-substituted (i + 2) amino acid have been readily synthesized from α-alkyl serines. The conformational analysis of such ß-lactam pseudopeptides conducted in CDCl(3) and DMSO-d(6) solutions using 1D- and 2D-NMR techniques revealed an equilibrium between ß-II turn and γ-turn conformers, which was ultimately modulated by the relative configuration of the -(ß-lactam)-(Aa)- residues. Long-range chiral effects on the α-lactam pseudopeptide conformers were also found when two (i) and (i + 3) chiral residues were attached to the termini of a central -(ß-lactam)-(Aib)- segment. In such mimetics, heterochiral (i) and (i + 3) residues reinforced a ß-II turn conformer, whereas homochiral corner residues stabilized an overlapped ß-II/ ß-I double turn motif. No ß-hairpin nucleation was observed in any instance. In good agreement with the conformers found in solution, ß-turned and open structures were also characterized by X-ray crystallography. Relative stabilities of the different conformers were estimated computationally at a B3LYP/6-31++G** calculation level, and finally, a conformation equilibrium model based on steric inter-residual interactions around the -(ß-lactam)-(i + 2)- segment was proposed to account for the observed chiral effects.

Conformation and chiral effects in α,ß,α-tripeptides.

Short α,ß,α-tripeptides comprising a central chiral trisubstituted ß(2,2,3)*-amino acid residue form unusual γ-turns and δ-turns in CDCl(3) and DMSO-d(6) solutions but do not form ß-turns. Thermal coefficients of backbone amide protons, 2D-NMR spectra, and molecular modeling revealed that these motifs were strongly dependent on the configuration (chiral effect) of the central ß-amino acid residue within the triad. Accordingly, SSS tripeptides adopted an intraresidual γ-turn like (C6) arrangement in the central ß-amino acid, whereas SRS diastereomers preferred an extended δ-turn (C9) conformation. A different SRS-stabilizing bias was observed in the crystal structures of the same compounds, which shared the extended δ-turn (C9) found in solution, but incorporated an additional extended ß-turn (C11) to form an overlapped double turn motif.

"Click" saccharide/beta-lactam hybrids for lectin inhibition.

Hybrid glycopeptide beta-lactam mimetics designed to bind lectins or carbohydrate recognition domains in selectins have been prepared according to a "shape-modulating linker" design. This approach was implemented using the azide-alkyne "click" cycloaddition reaction, and as shown by NMR/MD experiments, binding of the resulting mimetics to Ulex Europaeus Lectin-1 (UEL-1) occurred after a "bent-to-extended" conformational change around a partially rotatable triazolylmethylene moiety.

Synthesis of beta-lactam scaffolds for ditopic peptidomimetics.

[reaction: see text] Ring opening of alpha-substituted-alpha-methoxycarbonyl-N-nosylaziridines provides a practical access to enantiopure alpha,alpha'-disubstituted beta-lactam scaffolds, novel types of ditopic reverse turn surrogates. The procedure is general, short, and high yielding and starts from handy alpha-substituted serinates and alpha-amino acid derivatives.

Quantitative determination of formic acid in apple juices by (1)H NMR spectrometry.

A quantitative determination method of formic acid in apple juices is proposed by means of the proton nuclear magnetic resonance ((1)H NMR) technique. Formic acid gives a singlet signal at the 8.2-8.4ppm interval of the spectrum, and its area is used to determine the concentration of the acid. 1,3,5-Benzenetricarboxylic acid is added to the juice as an internal standard. Since the chemical shift of both species varies with the pH, ascorbic acid is also added to adjust it at 2.74 and to avoid the overlapping of the signals. Recoveries between 95 and 109% are obtained when the standard addition method is applied to the juices of five different cider apple varieties. The coefficient of variation obtained is 3.9% for intra-day repeatability (n=5), and 4.6% for inter-day repeatability (n=10). The limit of detection is 1.49mg/l, calculated from "3S(y/x)+intercept". The described method is direct and no previous derivatization is needed.

Hemangioma capilar lobulillar nasal gravídico / No disponible

El hemangioma capilar lobulillar, llamado tambiéninapropiadamente granuloma piogénico, es un tumorvascular benigno de rápido crecimiento y origen desconocido,que afecta la piel o mucosas de la cavidad oral yregión nasosinusal. Aportamos este caso por su localizacióninusual, realizándose además una revisión de laliteratura

Lobular capillary hemangioma, also inappropriatelynamed pyogenic granuloma, is a benign rapidly growingtumor of unknown origin that affects the skin and the oralcavity and sinonasal region mucosa. We provide this casedue to its unusual localization and we perform a literaturereviewm

Development of a new family of conformationally restricted peptides as potent nucleators of beta-turns. Design, synthesis, structure, and biological evaluation of a beta-lactam peptide analogue of melanostatin.

Novel enantiopure (i)-(beta-lactam)-(Gly)-(i+3) peptide models, defined by the presence of a central alpha-alkyl-alpha-amino-beta-lactam ring placed as the (i+1) residue, have been synthesized in a totally stereocontrolled way by alpha-alkylation of suitable N-[bis(trimethylsilyl)methyl]-beta-lactams. The structural properties of these beta-lactam pseudopeptides have been studied by X-ray crystallography, Molecular Dynamics simulation, and NOESY-restrained NMR simulated annealing techniques, showing a strong tendency to form stable type II or type II' beta-turns either in the solid state or in highly coordinating DMSO solutions. Tetrapeptide models containing syn- or anti-alpha,beta-dialkyl-alpha-amino-beta-lactam rings have also been synthesized and their conformations analyzed, revealing that alpha-alkyl substitution is essential for beta-turn stabilization. A beta-lactam analogue of melanostatin (PLG amide) has also been prepared, characterized as a type-II beta-turn in DMSO-d6 solution, and tested by competitive binding assay as a dopaminergic D2 modulator in rat neuron cultured cells, displaying moderate agonist activity in the micromolar concentration range. On the basis of these results, a novel peptidomimetic design concept, based on the separation of constraint and recognition elements, is proposed.

Quantitative determination of (-)-epicatechin in cider apple juices by (1)H NMR.

This paper reports a quantitative determination method of (-)-epicatechin in apple juices by measuring of its signal at 7.05 ppm in the (1)H NMR spectrum. It is a direct method that does not need any previous derivatization. 1,3,5-Benzenetricarboxylic acid was added to the juice as internal standard for the determination of the absolute concentration of (-)-epicatechin. Ascorbic acid was also added to avoid enzymatic oxidation of the phenolics and to adjust the pH at 2.74, since the chemical shift of some compounds varies with the pH. Standard addition method accomplished with the juices of two different varieties of apples gave recoveries between 95 and 109%. The precision of the method was tested for repeatability (n=5) and reproducibility (n=13) obtaining a coefficient of variation of 5.8 and 8.6%, respectively. Limit of detection, calculated from "3S(y/x)+intercept", is 24 mg l(-1).