Impaired cerebrovascular reactivity is associated with recurrent stroke in patients with severe intracranial arterial stenosis: A C02 BOLD fMRI study.

Background And Purpose: Severe intracranial atherosclerotic stenosis (SIAS) remains at risk of recurrent ischemic events despite intensive medical management. Exhausted cerebrovascular reserve seems to be associated with higher risk of recurrent stroke.

Materials And Methods: We used whole brain MRI to estimate basal perfusion using dynamic susceptibility contrast and cerebrovascular reactivity (CVR) to hypercapnic challenge (CO2 inhalation) using BOLD contrast, in 20 patients with symptomatic SIAS (>70%) of the middle cerebral artery (MCA) or the distal internal carotid artery.

Structural and pharmacological characteristics of chimeric peptides derived from peptide E and beta-endorphin reveal the crucial role of the C-terminal YGGFL and YKKGE motifs in their analgesic properties.

Peptide E (a 25-amino acid peptide derived from proenkephalin A) and beta-endorphin (a 31-amino acid peptide derived from proopiomelanocortin) bind with high affinity to opioid receptors and share structural similarities but induce analgesic effects of very different intensity. Indeed, whereas they possess the same N-terminus Met-enkephalin message sequence linked to a helix by a flexible spacer and a C-terminal part in random coil conformation, in contrast with peptide E, beta-endorphin produces a profound analgesia. To determine the key structural elements explaining this very divergent opioid activity, we have compared the structural and pharmacological characteristics of several chimeric peptides derived from peptide E and beta-endorphin.

Antimicrobial properties of brevinin-2-related peptide and its analogs: Efficacy against multidrug-resistant Acinetobacter baumannii.

Brevinin-2 related peptide (B2RP; GIWDTIKSMG(10)KVFAGKILQN(20)L.NH(2)), first isolated from skin secretions of the mink frog Lithobates septentrionalis, shows broad-spectrum antimicrobial activity but its therapeutic potential is limited by moderate hemolytic activity. The peptide adopts an alpha-helical conformation in a membrane-mimetic solvent but amphipathicity is low.

A glycine-leucine-rich peptide structurally related to the plasticins from skin secretions of the frog Leptodactylus laticeps (Leptodactylidae).

A glycine-leucine-rich peptide was isolated from norepinephrine-stimulated skin secretions of the Sante Fe frog Leptodactylus laticeps (Leptodactylidae) whose primary structure (Gly-Leu-Val-Asn-Gly-Leu-Leu-Ser-Ser-Val-Leu-Gly-Gly-Gly-Gln-Gly-Gly-Gly-Gly-Leu-Leu-Gly-Gly-Ile-Leu) contains the (GXXXG)(3) motif found in the plasticins, previously identified only in phyllomedusid frogs (Hylidae). Circular dichroism studies showed that the secondary structure of the peptide, termed plasticin-L1, was markedly solvent-dependent displaying a random coil conformation in water, a beta-sheet structure in methanol, and an alpha-helical conformation in 50% trifluoroethanol-water. A synthetic replicate of the peptide did not inhibit the growth of Escherichia coli or Staphylococcus aureus or lyse human erythrocytes at concentrations up to 500 microM.

Synthesis and structure of new 3,3,9,9-tetrasubstituted-2,4,8,10-tetraoxaspiro[5.5]undecane derivatives.

The configurational and conformational behavior of some new 3,3,9,9-tetrasubstituted-2,4,8,10-tetraoxaspiro[5.5]undecane derivatives with axial chirality was investigated by conformational analysis and variable temperature NMR experiments.

New [4.4]cyclophanes: molecular parallelograms, triangles, rhombuses, pentagons, and supramolecular constructions.

The fair or good yield synthesis of new [(4.4)(n)]cyclophanes (n = 1-5), starting from 1,4-bis(2-hydroxymethyl-5,5-dimethyl-1,3-dioxan-2-yl)benzene and several diacid-dichlorides, based on monomer and oligomer formation reactions (from 1 + 1 to 5 + 5), is reported. The structure and the complex architectures of the lattices for these cyclophanes are revealed by the X-ray molecular structure for five compounds, NMR investigations, and mass spectrometry measurements.

Design of potent, non-toxic antimicrobial agents based upon the naturally occurring frog skin peptides, ascaphin-8 and peptide XT-7.

The frog skin peptides, ascaphin-8 (GFKDLLKGAAKALVKTVLF.NH(2)) and XT-7 (GLLGPLLKIAAKVGSNLL.NH(2)), show broad-spectrum antimicrobial activity but their therapeutic potential is limited by toxicity against mammalian cells.

Effect of aminoisobutyric acid (Aib) substitutions on the antimicrobial and cytolytic activities of the frog skin peptide, temporin-1DRa.

Temporin-1DRa (HFLGTLVNLAKKIL.NH(2)), first isolated from the skin of the California red-legged frog Rana draytonii, shows broad-spectrum antimicrobial activity but its therapeutic potential is limited by its toxicity against mammalian cells. The cytolytic properties of cationic alpha-helical peptides are determined by a complex interaction between cationicity, hydrophobicity, conformation, and amphipathicity.

Chiral discrimination in host-guest supramolecular complexes. Understanding enantioselectivity and solid solution behaviors by using spectroscopic methods and chemical sensors.

Diastereomeric host-guest associations formed between permethylated-beta-cyclodextrin (TMbeta-Cd) and the two enantiomers of p-bromophenylethanol (pBrPE) were characterized in aqueous solution by NMR spectroscopy, revealing similar inclusion geometries and weak binding constants, whatever the guest configuration. These features were confirmed by hydrogenation experiments, and do not allow to account for the ability of TMbeta-Cd to resolve racemic pBrPE by successive crystallizations [Grandeury, A.; Petit, S.

High-resolution nuclear magnetic resonance spectroscopy studies of polysaccharides crosslinked by sodium trimetaphosphate: a proposal for the reaction mechanism.

An NMR spectroscopy study ((31)P, (1)H, (13)C) of the postulated crosslinking mechanism of sodium trimetaphosphate (STMP) on polysaccharides is reported using methyl alpha-D-glucopyranoside as a model. In a first step, reaction of STMP with Glc-OMe gives grafted sodium tripolyphosphate (STPP(g)). On the one hand, STTP(g) can react with a second alcohol functionality to give a crosslinked monophosphate.

Molecular rotors: design, synthesis, structural analysis, and silver complex of new [7.7]cyclophanes.

New molecular rotors, [7.7](2,6)pyridinocyclophanes (monomers and dimers) embedding 1,3-dioxanes in the bridges, were investigated by variable-temperature NMR, molecular modeling, and single-crystal X-ray diffractometry. The nitrogen-inside rotation of the pyridine ring is more hindered in the derivatives with longer distance between the bridges (i.

Development of cross-linked polystyrene-supported chiral amines featuring a fluorinated linker for gel-phase 19F NMR spectrometry monitoring of reactions.

Ten cross-linked polystyrene-supported, protected chiral amines featuring both a spacer, comprising from 5 to 15 atoms, and a fluorinated linker have been successfully prepared. The development of the monitoring technique by gel-phase 19F NMR spectrometry on cross-linked polystyrene derivatives proved to be of high value in four steps of the process, as shown by the comparison of data gathered from both a classic NMR spectrometer and elemental analysis. Gel-phase 19F NMR spectrometry, thus, constitutes a useful technique that complements IR and 13C NMR spectrometries for the qualitative monitoring of reactions.

Design and synthesis of new macrocyclic cyclophanes using 1,3-dioxane units as bridges: a molecular "rocking chair".

The design, synthesis and structural analysis of architecturally new cyclophanes (monomers, dimers, and trimers) are reported. Variable temperature NMR experiments reveal a regular, tandem dynamic in the cyclophane 2a that enables its description as a "molecular rocking chair". The NMR and X-ray structure investigations show important intra- and intermolecular aromatic pi-stacking interactions.

Structural investigation of hemicellulosic polysaccharides from Argania spinosa: characterisation of a novel xyloglucan motif.

Hemicellulose polymers were isolated from Argania spinosa leaf cell walls by sequential extractions with alkali. The structure of the two main polymers, xylan and xyloglucan, was investigated by enzyme degradation with specific endoglycosidases followed by analysis of the resulting fragments by high performance anion exchange chromatography (HPAEC) and matrix-assisted laser desorption ionisation-time of flight mass spectrometry (MALDI-TOF MS). The results show that A.

The basolateral sorting signals of the thyrotropin and luteinizing hormone receptors: an unusual family of signals sharing an unusual distal intracellular localization, but unrelated in their structures.

The mechanisms of the basolateral targeting of G protein-coupled receptors remain largely unknown. Mutagenesis experiments have allowed us to identify the basolateral sorting signals of the TSH and LH receptors expressed in Madin-Darby canine kidney cells and thyroid follicular FRT cells. Unexpectedly these signals (amino acids 731-746 and 672-689, respectively) share an unusual localization in the distal part of the intracellular domain of the receptors at a marked distance from the membrane.

Efficient synthesis of 3-furanosyl-6'-furanosylphosphinate through a tandem sequential radical process.

The sodium salt of hypophosphorous acid is shown to act as a double radical precursor in a double, sequential radical addition on 3-exo-methylenefuranose derivative 14 and 4-ethylenefuranose 10 to furnish phosphinates 18d in good overall yields. Unambiguous structural assignment establishes the high diastereoselection of the process.