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Conformational Mobility (conformational + mobility)

Distribution by Scientific Domains

Chemistry	60%

Selected Abstracts

Inhibition of acetylcholinesterase by physostigmine analogs: Conformational mobility of cysteine loop due to the steric effect of the alkyl chain

JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 2 2002
Enrico Gavuzzo
Abstract The effect of a series of physostigmine analogs on acetylcholinesterase activity was investigated. The second-order rate constant kon of the enzyme,inhibitor complex correlates with the conformational positioning of aromatic residues, especially Trp84, in the transition state complex. The van der Waals interactions are an important structural element of this conformational change. A transient mobility of the cysteine loop (Cys67,Cys94) was confined only to the presence of a significant steric effect. Even with this limitation, however, the steric effect seems to be an appropriate model for future tests on the "back door" hypothesis involving facilitated opening for faster product clearance. © 2002 Wiley Periodicals, Inc. J Biochem Mol Toxicol 16:64,69, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/jbt.10026 [source]

Novel tetracyclic imidazole derivatives: Synthesis, dynamic NMR study, and anti-inflammatory evaluation

JOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 3 2010
Renata Rup
A series of tetracyclic imidazole derivatives 9a,9v and 10a,10h are prepared by multistep route starting from the known tricyclic diketones 2a,2d. Intermediary dibenzooxepin[4,5- d]imidazoles (3a, 3c) and dibenzothiepin[4,5- d]imidazoles (3b, 3d) are N -protected to 4e, 4f and to the isomeric compounds 5a, 5b and 6a, 6b. The isomeric compounds 5 and 6 are separated. Compounds 4, 5, and 6 are formylated at C(2) to afford 7a,7j. In the last steps, aldehyde group is reduced, then alkylated to the two sets of isomeric ,-dimethylaminoalkyl derivatives 9a,9v. N -deprotection of 9i,9v led to the compounds 10a,10h. Assignment of the syn/anti structure to 5a and 6a was supported by 1D selective ROESY NMR spectra, whereas conformational mobility for the selected representatives 8a and 8b is studied by dynamic NMR. Activation energies (energy barriers for interconversion) are determined to be ,11.5 and 16.2 kcal/mol, respectively. A series of derivatives 9 and 10 were tested in vitro for their anti-inflammatory activity. J. Heterocyclic Chem., (2010). [source]

Influence of the cross-linking density on the main dielectric relaxation of poly(methyl acrylate) networks

POLYMER ENGINEERING & SCIENCE, Issue 10 2005
J.M. Meseguer Dueñas
A series of polymer networks of varying cross-linking density was prepared by copolymerization of methyl acrylate and ethyleneglycol dimethacrylate. The aim of this work is to study the influence of cross-linking on the conformational mobility of the polymer chains using dielectric relaxation spectroscopy (DRS) in the temperature range of the main dielectric relaxation. As expected, the temperature range in which glass transition takes place became wider with increasing crosslinking density. DRS results were analyzed using the Havriliak-Negami equation. Master Cole-Cole arcs could be drawn for all the networks. The arcs become more symmetric as cross-linking density increases, as a consequence of the different effect of cross-links on large and small scale mobility. The conformational mobility that produces the main relaxation is drastically reduced when the cross-linking density increases what reduces the relaxation strength, but it also gives a qualitative change of behavior, as shown by the temperature dependence of the relaxation strength. In the loosely cross-linked networks the relaxation strength decreases monotonously as temperature increases, as in the main dielectric relaxation of linear polymers. Nevertheless, in highly cross-linked networks the curve of relaxation strength against temperature presents a maximum. POLYM. ENG. SCI., 45:1336,1342, 2005. © 2005 Society of Plastics Engineers [source]

Molecule-Responsive Block Copolymer Micelles

CHEMISTRY - A EUROPEAN JOURNAL, Issue 16 2007
Yoshihiro Ishihara
Abstract Ring-opening metathesis polymerization was used to generate an ABC triblock copolymer, containing complementary diamidopyridine (DAP) and thymine (THY) outer blocks, which assembles into spherical aggregates held together by DAP,THY noncovalent interactions. Addition of THY-containing small guest molecules results in complete opening and deaggregation of the block copolymer micelle. This molecular recognition and macroscopic response shows high selectivity to the guest structure, and tolerates only a small amount of conformational mobility in the THY guest. On the other hand, addition of a small DAP-containing guest does not break the aggregates, but instead, results in new micelles which show a different selectivity profile from the parent morphology. We have examined the effect of a number of structural features in the block copolymers, on both the extent and selectivity of their macroscopic response to guests (that is, opening of the micelle). This study has resulted in a set of structural guidelines, which help in the design of effective molecule-responsive micelles for applications in selective drug delivery, sensing, and surface patterning. [source]

ILLUMINATING THE STRUCTURE AND FUNCTION OF CYS-LOOP RECEPTORS

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 10 2008
Stephan A Pless
SUMMARY 1Cys-loop receptors are an important class of ligand-gated ion channels. They mediate fast synaptic neurotransmission, are implicated in various ,channelopathies' and are important pharmacological targets. Recent progress in X-ray crystallography and electron microscopy has provided a considerable insight into the structure of Cys-loop receptors. However, data from these experiments only provide ,snapshots' of the proteins under investigation. They cannot provide information about the various conformations the protein adopts during transition from the closed to the open and desensitized states. 2Voltage-clamp fluorometry helps overcome this problem by simultaneously monitoring movements at the channel gate (through changes in current) and conformational rearrangements in a domain of interest (through changes in fluorescence) in real time. Thus, the technique can provide information on both transitional and steady state conformations and serves as a real time correlate of the channel structure and its function. 3Voltage-clamp fluorometry experiments on Cys-loop receptors have yielded a large body of data concerning the mechanisms by which agonists, antagonists and modulators act on these receptors. They have shed new light on the conformational mobility of both the ligand-binding and the transmembrane domain of Cys-loop receptors. [source]