Search results for "MIM"
showing 10 items of 645 documents
Picomolar inhibition of cholera toxin by a pentavalent ganglioside GM1os-calix[5]arene
2013
Cholera toxin (CT), the causative agent of cholera, displays a pentavalent binding domain that targets the oligosaccharide of ganglioside GM1 (GM1os) on the periphery of human abdominal epithelial cells. Here, we report the first GM1os-based CT inhibitor that matches the valency of the CT binding domain (CTB). This pentavalent inhibitor contains five GM1os moieties linked to a calix[5]arene scaffold. When evaluated by an inhibition assay, it achieved a picomolar inhibition potency (IC50 = 450 pM) for CTB. This represents a significant multivalency effect, with a relative inhibitory potency of 100000 compared to a monovalent GM1os derivative, making GM1os-calix[5]arene one of the most potent…
Self-assembly of janus dendrimers into uniform dendrimersomes and other complex architectures
2010
Janus Drug Delivery Vehicle Efficient drug delivery vehicles need to be produced in a limited size range and with uniform size distribution. The self-assembly of traditional small-molecule and polymeric amphiphiles has led to the production of micelles, liposomes, polymeric micelles, and polymersomes for use in drug delivery applications. Now, Percec et al. (p. 1009 ) describe the self-assembly of Janus-type (i.e., two-headed) dendrimers to produce monodisperse supramolecular constructs, termed “dendrimersomes,” and other complex architectures. The structures, which showed long-term stability as well as very narrow size distributions, were easily produced by the injection of an ethanolic so…
Selective recognition of neutral guests in an aqueous medium by a biomimetic calix[6]cryptamide receptor
2015
The design of artificial receptors that can efficiently work in water is a challenging research area. A possible biomimetic approach for the elaboration of such receptors consists of associating a hydrophobic cavity with a polar polyfunctional binding site. On this basis, a hydrophilic calix[6]cryptamide decorated with oligo(ethylene glycol) units (i.e. 8) was synthesized through an efficient [1 + 1] macrocyclization reaction as the key-step. The complexation of neutral molecules was evaluated by NMR spectroscopy through competition experiments either in apolar or aqueous media. In both media, host 8 can bind neutral species that display H-bonding acceptor and donor groups such as amides or…
Synthesis of enantiopure pyrrolidine-derived peptidomimetics and oligo-beta-peptides via nucleophilic ring-opening of beta-lactams.
2006
The synthesis of the two enantiomers of pyrrolidine-derived spiro beta-lactams by resolution with D- and L-Boc phenylalanine is described. The potential of these optically active spiro beta-lactams on the synthesis of peptidomimetics as analogues of melanostatin is evaluated. Theoretical studies of several models, at the Becke3LYP/6-31+G* level of theory, together with previous experimental evidences from our group, gathered by NMR, allow us to design structures that can efficiently mimic some biologically active peptide-type molecules. On the other hand, the spiro beta-lactams have shown their utility in the preparation of beta-peptides. As an example, a homo-tetra-beta-peptide was synthes…
Redox-responsive organometallic foldamers from ferrocene amino acid: Solid-phase synthesis, secondary structure and mixed-valence properties
2011
Oligoferrocenes Fmoc-Fca(n)-OMe (n=3-5) are assembled in a stepwise precise manner from Fmoc-protected ferrocene amino acid Fmoc-Fca-OH (H-Fca-OH = 1-amino-1'-ferrocene carboxylic acid; Fmoc = 9-fluorenylmethyloxycarbonyl) via amide bonds on solid supports by sequential Fmoc deprotection, acid activation and coupling steps. The resulting well-defined oligomers form ordered zigzag structures in THF solution with characteristic hydrogen bonding patterns. Electrochemical experiments reveal sequential oxidations of the individual ferrocene units in these peptides giving mixed-valent cations. Optical intervalence electron transfer is detected by intervalence transitions in the near-IR.
The Molecular Anatomy of Human Hsp60 and its Similarity with that of Bacterial Orthologs and Acetylcholine Receptor Reveal a Potential Pathogenetic R…
2012
Heat-shock protein 60 (Hsp60) is ubiquitous and highly conserved being present in eukaryotes and prokaryotes, including pathogens. This chaperonin, although typically a mitochondrial protein, can also be found in other intracellular sites, extracellularly, and in circulation. Thus, it can signal the immune system and participate in the development of inflammation and immune reactions. Both phenomena can be elicited by human and foreign Hsp60 (e.g., bacterial GroEL), when released into the blood by infectious agents. Consequently, all these Hsp60 proteins become part of a complex autoimmune response characterized by multiple cross reactions because of their structural similarities. In this s…
Biomimetic oxygen reduction by cofacial porphyrins at a liquid-liquid interface.
2012
Oxygen reduction catalyzed by cofacial metalloporphyrins at the 1,2-dichlorobenzene−water interface was studied with two lipophilic electron donors of similar driving force, 1,1'-dimethylferrocene (DMFc) and tetrathiafulvalene (TTF). The reaction produces mainly water and some hydrogen peroxide, but the mediator has a significant effect on the selectivity, as DMFc and the porphyrins themselves catalyze the decomposition and the further reduction of hydrogen peroxide. Density functional theory calculations indicate that the biscobaltporphyr- in, 4,5-bis(5-(2,8,13,17-tetraethyl-3,7,12,18-tetramethylporphyrinyl))-9,9-dimethylxanthene, Co2(DPX), actually catalyzes oxygen reduction to hydrogen p…
A phenoxo-bridged dicopper(ii) complex as a model for phosphatase activity: mechanistic insights from a combined experimental and computational study
2017
A μ-phenoxo-bis(μ2-1,3-acetato)-bridged dicopper(II) complex [CuII2(L1)(μ-O2CMe)2][NO3] (1) has been synthesized from the perspective of modeling phosphodiesterase activity. Structural characterization was done initially with 1·3Et2O (vapour diffusion of Et2O into MeOH solution of 1; poor crystal quality) and finally with its perchlorate salt [CuII2(L1)(μ-O2CMe)2][ClO4]·1.375MeCN·0.25H2O, crystallized from vapour diffusion of n-pentane into a MeCN–MeOH mixture (comparatively better crystal quality). An asymmetric unit of such a crystal contains two independent molecules of compositions [CuII2(L1)(μ-O2CMe)2][ClO4] and [CuII2(L1)(μ-O2CMe)2(MeCN)][ClO4] (coordinated MeCN with 0.75 occupancy), …
Functional superoxide dismutase mimics. Structural characterization and magnetic exchange interactions of copper(II)-N-substituted sulfonamide dimer …
2004
Dinuclear copper(II) complexes with N-substituted sulfonamide ligands as superoxide dismutase (SOD) mimics have been investigated. The new N-(thiazol-2-yl)toluenesulfonamide (Htz-tol) and N-(thiazol-2-yl)naphthalenesulfonamide (Htz-naf) ligands have been prepared and structurally characterized. The complexes derived from these ligands, [Cu(2)(tz-tol)(4)] (1) and [Cu(2)(tz-naf)(4)] (2), have been synthesized, and their crystal structure, magnetic properties, and EPR spectra were studied in detail. In both compounds the metal centers are bridged by four nonlinear triatomic NCN groups. The coordination geometry of the coppers in the dinuclear entity of 1 and 2 is distorted square planar with t…
Toward very potent, non-covalent organophosphonate inhibitors of cathepsin C and related enzymes by 2-amino-1-hydroxy-alkanephosphonates dipeptides
2013
Cathepsins play an important role in several human disorders and therefore the design and synthesis of their inhibitors attracts considerable interest in current medicinal chemistry approaches. Due to the presence of a strong sulphydryl nucleophile in the active center of the cysteine type cathepsins, most strategies to date have yielded covalent inhibitors. Here we present a series of non-covalent β-amino-α-hydroxyalkanephosphonate dipeptidic inhibitors of cathepsin C, ranking amongst the best low-molecular weight inhibitors of this enzyme. Their binding modes determined by molecular modelling indicate that the hydroxymethyl fragment of the molecule, not the phosphonate moiety, acts as a t…