Search results for "Models"
showing 10 items of 8211 documents
Synthesis of a potent photoreactive acidic γ-secretase modulator for target identification in cells.
2012
Supramolecular self-assembly of amyloidogenic peptides is closely associated with numerous pathological conditions. For instance, Alzheimer´s disease (AD) is characterized by abundant amyloid plaques originating from the proteolytic cleavage of the amyloid precursor protein (APP) by β- and γ-secretases. Compounds named γ-secretase modulators (GSMs) can shift the substrate cleavage specificity of γ-secretase toward the production of non-amyloidogenic, shorter Aβ fragments. Herein, we describe the synthesis of highly potent acidic GSMs, equipped with a photoreactive diazirine moiety for photoaffinity labeling. The probes labeled the N-terminal fragment of presenilin (the catalytic subunit of …
An "S"-shaped pentanuclear CuII cluster derived from the metal-assisted hydrolysis of pyCOpyCOpy: structural, magnetic and spectroscopic studies.
2007
Reaction of [Cu2(O2CMe)4(H2O)2] with 2,6-di-(2-pyridylcarbonyl)-pyridine (pyCOpyCOpy or dpcp) in MeCN–H2O 10 : 1, led to the pentanuclear copper(II) complex [Cu5(O2CMe)6{pyC(O)(OH)pyC(O)(OH)py}2] (1) which crystallizes in the triclinic P space group. The copper(II) atoms are arranged in an “S”-shaped configuration, and are bridged by the doubly deprotonated bis(gem-diol) form of the ligand, pyC(O)(OH)pyC(O)(OH)py2−. Magnetic susceptibility data indicate the interplay of both ferro- and antiferromagnetic intramolecular interactions stabilizing an S = 3/2 ground state. Fitting of the data according to a next-nearest-neighbour model {Ĥ = −[J1(Ŝ1Ŝ2 + Ŝ1′Ŝ2′) + J2(Ŝ2Ŝ3 + Ŝ3′Ŝ2′) + J3(Ŝ1Ŝ3 + Ŝ3′Ŝ…
Enantiospecific semisynthesis of (+)-almuheptolide-A, a novel natural heptolide inhibitor of the mammalian mitochondrial respiratory chain.
1998
The development of novel styryl lactone derivatives as bioactive compounds and the semisynthesis of both 4,5-dialkoxylated eight-membered-ring lactones with a heptolide skeleton (almuheptolide-A (1) type) and 7-alkoxylated delta-lactones with a saturated furanopyrone skeleton (etharvensin (8) type) have been successfully achieved from the chiral unsaturated alpha-pyrone altholactone (7). This new method is a direct and one-step enantiospecific alkoxylation of altholactone (7) in concentrated acid medium, followed by formation of the eight-membered-ring zeta-lactone. The reaction mechanism operating in the synthesis of the heptolide skeleton is postulated to be a direct Michael-type addition…
Two Novel Ternary Dicopper(II) μ-Guanazole Complexes with Aromatic Amines Strongly Activated by Quantum Dots for DNA Cleavage
2013
Two novel (μ-guanazole)-bridged binuclear copper(II) complexes with 1,10-phenanthroline (phen) or 2,2'-bipyridine (bipy), [Cu2(μ-N2,N4-Hdatrz)(phen)2(H2O)(NO3)4] (1) and [Cu2(μ-N1,N2-datrz)2(μ-OH2)(bipy)2](ClO4)2 (2) (Hdatrz = 3,5-diamino-1,2,4-triazole = guanazole), have been prepared and characterized by X-ray diffraction, spectroscopy, and susceptibility measurements. Compounds 1 and 2 differ in the aromatic amine, which acts as a coligand, and in the Cu···Cu'-bridging system. Compound 1, which contains two mono-bridged copper ions, represents the first example of a discrete Cu-(NCN-trz)-Cu' complex. Compound 2, with two triply bridged copper ions, is one of the few compounds featuring a…
Development of Bimetallic Titanocene−Ruthenium−Arene Complexes As Anticancer Agents: Relationships between Structural and Biological Properties
2010
A series of bimetallic titanium-ruthenium complexes of general formula [(η(5)-C(5)H(5))(μ-η(5):κ(1)-C(5)H(4)(CR(2))(n)PR'R'')TiCl(2)](η(6)-p-cymene)RuCl(2) (n = 0, 1, 2 or 4; R = H or Me; R' = H, Ph, or Cy; R'' = Ph or Cy) have been synthesized, including two novel compounds as well as two cationic derivatives of formula [(η(5)-C(5)H(5))(μ-η(5):κ(1)-C(5)H(4)(CH(2))(n)PPh(2))TiCl(2)] [(η(6)-p-cymene)RuCl](BF(4)) (n = 0 or 2). The solid state structure of two of these compounds was also established by X-ray crystallography. The complexes showed a cytotoxic effect on human ovarian cancer cells and were markedly more active than their Ti or Ru monometallic analogues titanocene dichloride and RA…
Study of the influence of the bridge on the magnetic coupling in cobalt(II) complexes.
2009
Two new cobalt(II) complexes of formula [Co(2)(bta)(H(2)O)(6)](n) x 2nH(2)O (1) and [Co(phda)(H(2)O)](n) x nH(2)O (2) [H(4)bta = 1,2,4,5-benzenetetracarboxylic acid, H(2)phda = 1,4-phenylenediacetic acid] have been characterized by single crystal X-ray diffraction. Compound 1 is a one-dimensional compound where the bta(4-) ligand acts as 2-fold connector between the cobalt(II) ions through two carboxylate groups in para-conformation. Triply bridged dicobalt(II) units occur within each chain, a water molecule, a carboxylate group in the syn-syn conformation, and an oxo-carboxylate with the mu(2)O(1);kappa(2)O(1),O(2) coordination mode acting as bridges. Compound 2 is a three-dimensional comp…
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…
Structure of a molluscan hemocyanin didecamer (HtH1 from Haliotis tuberculata) at 12 Å resolution by cryoelectron microscopy
2000
A 12 A resolution three-dimensional density map of the Haliotis tuberculata hemocyanin type 1 (HtH1) didecamer has been obtained by cryoelectron microscopy of unstained molecules and angular reconstitution. The dyad symmetry of the 8 MDa D5 HtH1 didecamer, formed by the pairing of two asymmetric 4 MDa ring-like C5 decamers, is emphasised. The major and minor surface helical grooves of the didecamer are well defined, in agreement with earlier data on molluscan hemocyanins. The location of the obliquely orientated repeating unit, a subunit dimer, within the decamer has been defined. Following interactive extraction of this dimer, several new structural features of the dimer and of the subunit…
Structure of the altitude adapted hemoglobin of Guinea pig in the R2-state
2010
Background: Guinea pigs are considered to be genetically adapted to a high altitude environment based on the consistent finding of a high oxygen affinity of their blood. Methodology/Principal Findings: The crystal structure of guinea pig hemoglobin at 1.8 A u resolution suggests that the increased oxygen affinity of guinea pig hemoglobin can be explained by two factors, namely a decreased stability of the Tstate and an increased stability of the R2-state. The destabilization of the T-state can be related to the substitution of a highly conserved proline (P44) to histidine (H44) in the a-subunit, which causes a steric hindrance with H97 of the b-subunit in the switch region. The stabilizatio…
Ambident PCN Heterocycles: N- and P-Phosphanylation of Lithium 1,3-Benzazaphospholides
2009
Synthetic and structural aspects of the phosphanylation of 1,3-benzazaphospholides 1(Li), ambident benzofused azaphosphacyclopentadienides, are presented. The unusual properties of phospholyl-1,3,2-diazaphospholes inspired us to study the coupling of 1(Li) with chlorodiazaphospholene 2, which led to the N-substituted product 3. Reaction of 1(Li) with chlorodiphenyl- and chlorodicyclohexylphosphane likewise gave N-phosphanylbenzazaphospholes 4 and 5, whereas with the more bulky di-tert-butyl- and di-1-adamantylchlorophosphanes, the diphosphanes 6 and 7 are obtained; in the case of 7 they are isolated as a dimeric LiCl(THF) adduct. Structural information was provided by single-crystal X-ray d…