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Conformational Properties (conformational + property)
Selected AbstractsUnexpected Conformational Properties of 1-Trifluoromethyl-1-Silacyclohexane, C5H10SiHCF3: Gas Electron Diffraction, Low-Temperature NMR Spectropic Studies, and Quantum Chemical Calculations,CHEMISTRY - A EUROPEAN JOURNAL, Issue 6 2007Georgiy Abstract The molecular structure of axial and equatorial conformers of 1-trifluoromethyl-1-silacyclohexane, (C5H10SiHCF3), as well as the thermodynamic equilibrium between these species was investigated by means of gas electron diffraction (GED), dynamic nuclear magnetic resonance (DNMR) spectroscopy, and quantum chemical calculations (B3LYP, MP2, and CBS-QB3). According to GED, the compound exists as a mixture of two Cs symmetry conformers possessing the chair conformation of the six-membered ring and differing in the axial or equatorial position of the CF3 group (axial=58(12) mol,%/equatorial=42(12) mol,%) at T=293,K. This result is in a good agreement with the theoretical prediction. This is, however, in sharp contrast to the conformational properties of the cyclohexane analogue. The main structural feature for both conformers is the unusually long exocyclic bond length SiC 1.934(10),Å. A low-temperature 19F,NMR experiment results in an axial/equatorial ratio of 17(2) mol,%:83(2) mol,% at 113,K and a ,G,, of 5.5(2),kcal,mol,1. CBS-QB3 calculations in the gas-phase and solvation effect calculations using the PCM(B3LYP/6-311G*) and IPCM(B3LYP/6-311G*) models were applied to estimate the axial/equatorial ratio in the 100,300,K temperature range, which showed excellent agreement with the experimental results. The minimum energy pathways for the chair-to-chair inversion of trifluoromethylsilacyclohexane and methylsilacyclohexane were also calculated using the STQN(Path) method. [source] Conformational properties of bacterial DnaK and yeast mitochondrial Hsp70FEBS JOURNAL, Issue 12 2005-helical subdomain, Role of the divergent C-terminal Among the eukaryotic members of the Hsp70 family, mitochondrial Hsp70 shows the highest degree of sequence identity with bacterial DnaK. Although they share a functional mechanism and homologous co-chaperones, they are highly specific and cannot be exchanged between Escherichia coli and yeast mitochondria. To provide a structural basis for this finding, we characterized both proteins, as well as two DnaK/mtHsp70 chimeras constructed by domain swapping, using biochemical and biophysical methods. Here, we show that DnaK and mtHsp70 display different conformational and biochemical properties. Replacing different regions of the DnaK peptide-binding domain with those of mtHsp70 results in chimeric proteins that: (a) are not able to support growth of an E. coli DnaK deletion strain at stress temperatures (e.g. 42 °C); (b) show increased accessibility and decreased thermal stability of the peptide-binding pocket; and (c) have reduced activation by bacterial, but not mitochondrial co-chaperones, as compared with DnaK. Importantly, swapping the C-terminal ,-helical subdomain promotes a conformational change in the chimeras to an mtHsp70-like conformation. Thus, interaction with bacterial co-chaperones correlates well with the conformation that natural and chimeric Hsp70s adopt in solution. Our results support the hypothesis that a specific protein structure might regulate the interaction of Hsp70s with particular components of the cellular machinery, such as Tim44, so that they perform specific functions. [source] Conformational properties of thiophene oligomersJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 4 2000Salvatore Millefiori The molecular geometries and the torsional potentials about the inter-ring C-C bond in ,-oligothiophenes (,-nTh, n=2,4) have been calculated by means of conventional ab initio and density functional theory (DFT) calculations employing the hybrid B3LYP and BH&HLYP functionals. The position and the energetics of the critical points in the potential energy curve generated by rotation about the inter-ring CC bond are shown to be dependent on the computational method. DFT calculations, in comparison with MP2 calculations, favour conjugative interactions, while steric and coulombic interactions are equally treated by both methods. On oligomerization the electron delocalisation increases slightly, the p-charge being preferentially confined within the rings, although it is sufficient to move the molecular structure towards co-planarization and to increase the barrier through the perpendicular conformation. The IR and Raman spectra on the relevant rotamers of ,-2Th have been computed at HF/6,31G* and B3LYP/6,31G* levels. The comparison with the experiment is excellent. It has been found that small twisting from the planar conformation has no apparent effects, while 90° twisting and isomerization to the syn-gauche form produce significant frequency and intensity variations which could be useful probes in conformational studies. The simulated IR and Raman spectra of the ,-2Th rotamers are consistent with a small,-electron delocalisation between the rings. [source] Conformational properties of the macrocyclic trichothecene mycotoxin verrucarin A in solutionMAGNETIC RESONANCE IN CHEMISTRY, Issue 12 2008Georgia Fragaki Abstract Phase-sensitive nuclear Overhauser enhancement spectroscopy (NOESY) experiments, 3J couplings and computational molecular modeling (MM2* and MMFF force fields) were employed to examine the conformational properties of verrucarin A in chloroform solutions. The MMFF force field calculations resulted in a family of 12 low-energy structures along with their populations, the latter being determined by the NMR analysis of molecular flexibility in solution(NAMFIS) deconvolution analysis. The concluded model was capable of reproducing successfully the experimental NOESY cross-peak volumes and the proton-coupling constants. Among the 12 conformers, the one which was similar to the structure of verrucarin A in the solid state was the predominant accounting for 75% of the total relative population, although other low-energy conformations contributed to a lesser degree in order to explain the experimental data. Copyright © 2008 John Wiley & Sons, Ltd. [source] Synthesis and Properties of New Nucleotide Analogues Possessing Squaramide Moieties as New Phosphate Isosters,EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 24 2005Kohji Seio Abstract New analogues of 2,-deoxynucleotides and ribonucleotides incorporating a unique squaramide structure were synthesized. Because of the strong acidity of this moiety (pKa = 2.3), these nucleotide analogues exist in a monoanionic form, which can be regarded as an electronic isoster of 5,-nucleotides under physiological conditions. The synthesis of the nucleotide analogues was achieved through the condensation of 5,- or 3,-aminonucleosides with dimethyl squarate, whilst the selective removal of the methyl group was effectively accomplished by treatment with sodium bromide. In addition, we also synthesized 3,,5,-cyclic nucleotide analogues from the 3,,5,-diazidonucleoside derivatives. NMR analysis revealed that their ribose puckering was of an N-type form, identical to that in cAMP and cGMP. Because of the unique structural, electronic, and conformational properties of squaramide-type nucleotide analogues, these analogues should be quite interesting as potential biologically active compounds such as antiviral and anticancer agents. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source] Solvent-Dependent Conformational Behaviour of Model Tetrapeptides Containing a Bicyclic Proline MimeticEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 22 2004Andrea Trabocchi Abstract Two model tetrapeptides containing bicyclic analogues of either D - or L -proline were synthesised and their conformational properties were studied by NMR in different solvent systems and by molecular modelling techniques. Compound 1, with the bicyclic D -proline mimetic in the i+1 position, generated a unique trans isomer, and the peptide showed a well organised structure, in accordance with the tendency of D -proline to act as a good turn inducer with respect to its enantiomer. Peptide 2 displayed structures equilibrating from type I,II to type VI ,-turns, thus confirming the hypothesised relationship between the chirality of BGS/Bgs and proline enantiomers on nucleating compact turns. Moreover, such behaviour suggested a tool for peptidomimetic design of reverse turn peptides containing BGS/Bgs bicyclic proline mimetics, as the choice of chirality might influence the generation either of compact ,- and ,-turns or of flexible equilibrating reverse turn structures. The effect of solvent on conformational behaviour was also studied. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004) [source] Response of native and denatured hen lysozyme to high pressure studied by 15N/1H NMR spectroscopyFEBS JOURNAL, Issue 6 2001Yuji O. Kamatari High-pressure 15N/1H NMR techniques were used to characterize the conformational fluctuations of hen lysozyme, in its native state and when denatured in 8 m urea, over the pressure range 30,2000 bar. Most 1H and 15N signals of native lysozyme show reversible shifts to low field with increasing pressure, the average pressure shifts being 0.069 ± 0.101 p.p.m. (1H) and 0.51 ± 0.36 p.p.m. (15N). The shifts indicate that the hydrogen bonds formed to carbonyl groups or water molecules by the backbone amides are, on average, shortened by ,,0.02 Å as a result of pressure. In native lysozyme, six residues in the , domain or at the ,/, domain interface have anomalously large nonlinear 15N and 1H chemical-shift changes. All these residues lie close to water-containing cavities, suggesting that there are conformational changes involving these cavities, or the water molecules within them, at high pressure. The pressure-induced 1H and 15N shifts for lysozyme denatured in 8 m urea are much more uniform than those for native lysozyme, with average backbone amide shifts of 0.081 ± 0.029 p.p.m. (1H) and 0.57 ± 0.14 p.p.m. (15N). The results show that overall there are no significant variations in the local conformational properties of denatured lysozyme with pressure, although larger shifts in the vicinity of a persistent hydrophobic cluster indicate that interactions in this part of the sequence may rearrange. NMR diffusion measurements demonstrate that the effective hydrodynamic radius of denatured lysozyme, and hence the global properties of the denatured ensemble, do not change detectably at high pressure. [source] Anomalous conformational properties of PEO in H2O and D2O by SANS, PCS and Raman scatteringJOURNAL OF APPLIED CRYSTALLOGRAPHY, Issue 3-1 2000C. Branca PEO solutions in water and heavy water have been investigated using SANS, PCS and Raman spectroscopy. The employement of these techniques allows to carry out a comparison between the diffusive properties of PEO/H2O and PEO/D2O systems, in order to study the coil conformation dependence on temperature and concentration. The data reveal the different conformational properties of PEO in the two solvents which have been attributed to a different solvent quality of H2O and D2O. These results provide evidence to the fact that the properties of macromolecules, even of simple structure, can be influenced by the isotopic composition of the solvent. [source] Structure elucidation, conformational analysis and thermal effects on membrane bilayers of an antimicrobial myricetin ether derivativeJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 3 2001C. Demetzos The membrane perturbing 3,7,4,,5,-tetramethyl ether of myricetin 1 was isolated from Cistus monspelien-sis L. Its structure was elucidated and its conformational properties were explored using a combination of 2D NMR spectroscopy and computational chemistry. The obtained results showed that compound 1 adopts four enantiomeric pairs of low energy conformers characterized: (a) by an aromatic ring B twisted through rotation about C2-C1, bond from the rigid isoflavone ring; (b) a 4,-O-CH3 bond oriented out of the plane with equal probability upwards or downwards the phenyl ring B, while all the other O-CH3 bonds are oriented in the plane of the aryl ring. Two of these enantiomeric pairs are lowest in energy. These possible bioactive con-formers are possibly stabilized by van Der Waals interactions. The 3,,5-diacetyl derivative 2 of compound 1 was synthesized and its structure elucidation was achieved based on the chemical shift assignment of the parent compound 1. The Differential Scanning Calorimetry (DSC) results revealed that the degree of the thermal effects exerted by the flavonoids at dipalmitoylphosphatidyl choline (DPPC) bilayers followed the order 1 > 2 > myricetin. Their antimicrobial activity against Gram positive bacteria followed the same order. [source] Synthesis of 15N-, 13C-, and 2H-labeled methanandamide analogsJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 2 2003Fen-Mei Yao Abstract Four isotopically labeled, metabolically stable analogs of arachidony-lethanolamide (anandamide), an endogenous cannabinoid ligand, were synthesized via a five-step reaction sequence starting from arachidonic acid. These stable methanandamide derivatives will serve as probes for studying the conformational properties of anandamide in model membrane systems using solid-state NMR spectroscopy. The synthetic methods described can be applied to the preparations of other anandamide analogs with isotopic labeling in different positions of the molecule, which could be utilized in biochemical and pharmacological experiments. Copyright © 2002 John Wiley & Sons, Ltd. [source] New antitumour cyclic astin analogues: synthesis, conformation and bioactivityJOURNAL OF PEPTIDE SCIENCE, Issue 2 2004Dr Filomena Rossi Abstract Astins, antitumour cyclic pentapeptides, were isolated from the Aster tataricus. Their chemical structures, consist of a 16-membered ring system containing a unique ,,,-dichlorinated proline [Pro(Cl)2], other non-coded amino acid residues and a cis conformation in one of the peptide bonds. The astin backbone conformation, along with the cis peptide bond in which the ,,,-dichlorinated proline residue is involved, was considered to play an important role in their antineoplastic activities on sarcoma 180A and P388 lymphocytic leukaemia in mice, but the scope and potential applications of this activity remain unclear. With the aim at improving our knowledge of the conformational properties influencing the bioactivity in this class of compounds, new astin-related cyclopeptides were synthesized differing from the natural products by the presence of some non-proteinogenic amino acid residues: Aib, Abu, -(S),3 -hPhe and a peptide bond surrogate (-SO2 -NH-). The analogues prepared c(-Pro-Thr-Aib-,3 -Phe-Abu-), c[Pro-Thr-Aib-(S),3 -hPhe-Abu], c[Pro-Abu-Ser-(S),3 -hPhe,(CH2 -SO2 -NH)-Abu] and c[Pro-Thr-Aib-(S),3 -hPhe,(CH2 -SO2 -NH)-Abu] were synthesized by classical methods in solution and tested for their antitumour effect. These molecules were studied by crystal-state x-ray diffraction analysis and/or solution NMR and MD techniques. Copyright © 2003 European Peptide Society and John Wiley & Sons, Ltd. [source] Probing the shape of a hydrophobic pocket in the active site of , -opioid antagonistsJOURNAL OF PEPTIDE SCIENCE, Issue 7 2001Vincenzo Santagada Abstract The change of selectivity and the induction of antagonism by the insertion of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) in the second position of several opioid peptides have led to the interpretation of Tyr-Tic as a specific message domain for , -opioid antagonists and to the discovery of dipeptides with substantial opioid activity. Selectivity and activity increase enormously when Tyr is substituted by 2,,6,-dimethyl tyrosine (Dmt), hinting that the side chain of Dmt fits a hydrophobic cavity of the receptor very tightly and precisely. We have investigated the specificity of this fit by systematic changes of the substituents on the aromatic ring of Tyr. Mono- and disubstitutions different from 2,,6,- invariably lead to catastrophic decreases of activity. The only substitution compatible with retention of substantial antagonism is 2,-methyl. An analysis of the conformational properties of all analogues reveals that substitutions do not affect the global shape of the molecule significantly. Accordingly, it is possible to use the shape of the different side chains to map the hydrophobic cavity of the receptor. The resulting complementary image is funnel shaped. Copyright © 2001 European Peptide Society and John Wiley & Sons, Ltd. [source] Comparative DFT study on the role of conformers in the ruthenium alkylidene-catalyzed ROMP of norborn-2-eneJOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 11 2008Sergej Naumov Abstract Comparative quantum chemical calculations on the reaction pathways for the formation of ruthena(IV)cyclobutanes from both 1st - and 2nd -generation Grubbs catalysts of the general formula RuX2(L)(L,)(CH2) (L,=,PCy3 or 1,3-dimesityl-4,5-dihydroimidazolin-2-ylidene, L,,=,PCy3) and norborn-2-ene (NBE) were carried out on the B3LYP/LACVP** level in dependence on the ligand X,=,I, Br, Cl, and F. The mechanism proposed by Straub for the formation of (one) active and (three) inactive NBE,Ru,carbene complexes for non-cyclic alkenes was applied to the cyclic alkene NBE. In RuX2(PCy3)2(CH2), the inactive NBE,Ru,carbene complex is energetically more stable than the active one; however, in RuX2(IMesH2)(PCy3)(CH2), the active NBE,Ru,carbene complex is more stable than the inactive one. In due consequence, the possible rate limiting barrier for the conversion of the NBE,Ru,carbene complex into the corresponding metallocyclobutane (MCB) is systematically larger in the case of 1st -generation Grubbs catalysts than of 2nd -generation Grubbs catalysts due to an additional re-arrangement for the formation of an active , -complex from the more stable (inactive) conformer. This correlates with the observed reactivity of both types of initiators. There is a strong influence of the ligands L and X on the conformational properties and relative stabilities of the 14-electron intermediates, which has a direct effect on the distribution of the inactive and active conformations of the corresponding Ru,carbene,NBE complexes. A direct correlation between the conformational properties of the 14-electron intermediates and the relative stabilities of the active Ru,carbene,NBE complexes was observed. Copyright © 2008 John Wiley & Sons, Ltd. [source] Conformational properties of the macrocyclic trichothecene mycotoxin verrucarin A in solutionMAGNETIC RESONANCE IN CHEMISTRY, Issue 12 2008Georgia Fragaki Abstract Phase-sensitive nuclear Overhauser enhancement spectroscopy (NOESY) experiments, 3J couplings and computational molecular modeling (MM2* and MMFF force fields) were employed to examine the conformational properties of verrucarin A in chloroform solutions. The MMFF force field calculations resulted in a family of 12 low-energy structures along with their populations, the latter being determined by the NMR analysis of molecular flexibility in solution(NAMFIS) deconvolution analysis. The concluded model was capable of reproducing successfully the experimental NOESY cross-peak volumes and the proton-coupling constants. Among the 12 conformers, the one which was similar to the structure of verrucarin A in the solid state was the predominant accounting for 75% of the total relative population, although other low-energy conformations contributed to a lesser degree in order to explain the experimental data. Copyright © 2008 John Wiley & Sons, Ltd. [source] Studies on inclusion complexes of calix[4]arenes capped by diamide bridges with small organic molecules,MAGNETIC RESONANCE IN CHEMISTRY, Issue 8 2008Barbara Balázs Abstract The inclusion of small neutral organic guests (acetonitrile, toluene, pyrazine, butylamine, nitromethane) by cyclic calix[4]arene diamide receptors was studied by 1H NMR spectroscopy. The binding constants determined by 1H NMR titration, and the results obtained by T1 relaxation measurements and DOSY confirm the importance of the acidity of the CH bond of the guests and highlight the role of steric interactions including conformational properties of the receptors in the recognition process. Copyright © 2008 John Wiley & Sons, Ltd. [source] The hydrodynamic and conformational properties of denatured proteins in dilute solutionsPROTEIN SCIENCE, Issue 1 2010Guy C. Berry Abstract Published data on the characterization of unfolded proteins in dilute solutions in aqueous guanidine hydrochloride are analyzed to show that the data are not fit by either the random flight or wormlike chain models for linear chains. The analysis includes data on the intrinsic viscosity, root-mean-square radius of gyration, from small-angle X-ray scattering, and hydrodynamic radius, from the translational diffusion coefficient. It is concluded that residual structure consistent with that deduced from nuclear magnetic resonance on these solutions can explain the dilute solution results in a consistent manner through the presence of ring structures, which otherwise have an essentially flexible coil conformation. The ring structures could be in a state of continual flux and rearrangement. Calculation of the radius of gyration for the random-flight model gives a similar reduction of this measure for chains joined at their endpoints, or those containing loop with two dangling ends, each one-fourth the total length of the chain. This relative insensitivity to the details of the ring structure is taken to support the behavior observed across a range of proteins. [source] Investigating the structural properties of amyloid-like fibrils formed in vitro from ,2 -microglobulin using limited proteolysis and electrospray ionisation mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 11 2006Sarah L. Myers The protein ,2 -microglobulin (,2m) aggregates to form classical amyloid fibrils in patients undergoing long-term haemodialysis. Amyloid-like fibrils with a cross- , fold can also be formed from wild-type ,2m under acidic conditions in vitro. The morphology of such fibrils depends critically on the conditions used: incubation of ,2m in low ionic strength buffers at pH 2.5 results in the formation of long (µm), straight fibrils while, at pH 3.6, short (<500,nm) fibrils form. At higher ionic strengths (0.2,0.4,M) at pH 1.5,3.6, the fibrils have a distinct curved and nodular morphology. To determine the conformational properties of ,2m within in vitro fibrils of different morphologies, limited proteolysis of each fibril type using pepsin was performed and the resulting peptide fragments identified by tandem mass spectrometry. For comparison, the proteolytic degradation patterns of monomeric ,2m and seven synthetic peptides spanning the entire sequence of the intact protein were similarly analysed. The results show that fibrils with different morphologies result in distinct digestion patterns. While the curved, worm-like fibrils are relatively weakly protected from proteolysis, the long, straight fibrils formed at pH 2.5 at low ionic strength show only a single cut-site at Val9, demonstrating that substantial refolding of the initially acid-denatured and unprotected state of ,2m occurs during assembly. The data demonstrate that the organisation of the polypeptide chain in fibrils with different morphological features differs considerably, despite the fact that the fibrils possess a common cross- , architecture. Copyright © 2006 John Wiley & Sons, Ltd. [source] Synthesis, crystal structure and spectroscopic properties of a novel carbacylamidophosphate: N -(3-nitrobenzoyl)- N,,N,,-bis(tert -butyl)phosphoric triamideACTA CRYSTALLOGRAPHICA SECTION B, Issue 4 2009Khodayar Gholivand The new compound N -(3-nitrobenzoyl)- N,,N,,-bis(tert -butyl)phosphoric triamide was synthesized by reacting 3-nitrobenzoyl phosphoramidic dichloride and tert -butyl amine, and characterized by multinuclear (1H, 13C and 31P) NMR and FTIR spectroscopy techniques. Structural and conformational properties were analyzed using single-crystal X-ray diffraction, vibrational spectra and theoretical calculations. The crystal structure contains three symmetry-independent disordered molecules, connected via intermolecular N,H...O=P and N,H...O=C hydrogen bonds to form a centrosymmetric hexameric chain extended along the [2,1,] direction. The disorder is mainly caused by rotation of the tert -butyl groups around the C,N bonds. [source] (2R,3R,5R)-2-[(2R,3aS,6aR)-2,3,3a,4,5,6a-Hexahydrofuro[2,3- b]furan-2-yl]-5-isopropenyl-2,3-dimethylcyclohexanone and (4aR,5S,7R)-5-isopropenyl-7,8,8-trimethyl-2,3,4,4a,5,6,7,8-octahydronaphthalene-4a-carbonitrileACTA CRYSTALLOGRAPHICA SECTION C, Issue 9 2000Dianne D. Ellis The molecular structures of two chiral cyclohexanones based on R -(,)-carvone, C17H26O3, (I), and C17H23NO, (II), are reported here. The six-membered ring in (I) is in a chair conformation with the two fused five-membered rings of the furofuranyl substituent in a cis configuration. Compound (II) contains a decalin group; one ring has the chair form whilst the other is in a half-boat conformation. Both products have been characterized spectroscopically, however, neither NMR nor IR results could prove the stereochemistry at each chiral centre unambiguously. The crystal analyses were used to examine conformational properties of the compounds. [source] 3-Imidazolyl-Substituted Flavans as Potential Antifungal Agents: Synthesis, Stereochemical Properties, and Antifungal ActivityARCHIV DER PHARMAZIE, Issue 9 2009Saeed Emami Abstract A new series of 3-imidazolyl-substituted flavan derivatives being equipped with a N -(phenethyl)-azole scaffold as the common pharmacophore of azole antifungals, were synthesized. The stereochemical and conformational properties of compounds were also characterized by 1H-NMR data. The results of the antifungal evaluation of trans -3-imidazolyl-substituted flavan-4-ones and (Z) -trans -3-imidazolyl-substituted flavan-4-one oximes in comparison with the reference drug fluconazole indicated that most target compounds possessed significant in-vitro antifungal activities against the tested fungi, comparable or superior to fluconazole. [source] Limited conformational change of ,-lactoglobulin when adsorbed at the air,water interfaceBIOPOLYMERS, Issue 4-5 2002Marcel B. J. Meinders Abstract Detailed insight can be obtained from proteins at and near the air,water interface using external reflection IR and circular dichroism techniques. Besides information on local protein concentrations and surface layer thickness, it is shown that ,-lactoglobulin displays a limited unfolding at the interface. The conformational change is comparable to that observed upon heat-induced aggregation of the protein and can be understood in view of the high surface concentration of the protein (,40% volume fraction). The layer thickness and the conformational properties of the protein do not depend on the bulk concentration. After adsorption of ,-lactoglobulin to a preformed lipid monomolecular layer a similar conformational change is induced, suggesting that the folding properties of the protein itself determine the extent of conformational changes at the interfaces. © 2002 Wiley Periodicals, Inc. Biopolymers (Biospectroscopy) 67: 319,322,2002 [source] Trifluoroethanol and binding to model membranes stabilize a predicted turn in a peptide corresponding to the first extracellular loop of the angiotensin II AT1A receptorBIOPOLYMERS, Issue 1 2002Roberto K. Salinas Abstract Homology modeling of the angiotensin II AT1A receptor based on rhodopsin,s crystal structure has assigned the 92,100 (YRWPFGNHL) sequence of the receptor to its first extracellular loop. Solution and membrane-bound conformational properties of a peptide containing this sequence (EL1) were examined by CD, fluorescence, and 1H-NMR. CD spectra in aqueous solution revealed an equilibrium between less organized and folded conformers. NMR spectra indicated the coexistence of trans and cis isomers of the Trp3,Pro4 bond. A positive band at 226 nm in the CD spectra suggested aromatic ring stacking, modulated by EL1's ionization degree. CD spectra showed that trifluoroethanol (TFE), or binding to detergent micelles and phospholipid bilayers, shifted the equilibrium toward conformers with higher secondary structure content. Different media gave rise to spectra suggestive of different ,-turns. Chemical shift changes in the NMR spectra corroborated the stabilization of different conformations. Thus, environments of lower polarity or binding to interfaces probably favored the formation of hydrogen bonds, stabilizing ,-turns, predicted for this sequence in the whole receptor. Increases in Trp3 fluorescence intensity and anisotropy, blue shifts of the maximum emission wavelength, and pK changes also evinced the interaction between EL1 and model membranes. Binding was seen to depend on both hydrophobic and electrostatic interactions, as well as lipid phase packing. Studies with water-soluble and membrane-bound fluorescence quenchers demonstrated that Trp3 is located close to the water,membrane interface. The results are discussed with regard to possible implications in receptor folding and function. © 2002 Wiley Periodicals, Inc. Biopolymers 65: 21,31, 2002 [source] Electrospray-ionization mass spectrometry as a tool for fast screening of protein structural propertiesBIOTECHNOLOGY JOURNAL, Issue 1 2009Rita Grandori Abstract Since the early 1990s, electrospray-ionization mass spectrometry (ESI-MS) has encountered growing interest as a complementary tool to established biochemical and biophysical methods for investigating protein structure and conformation. Nowadays, applications of ESI-MS to protein investigation span from the area of analytical biochemistry to that of structural biology. This review focuses on applications of this technique to the analysis of protein conformational properties and molecular interactions, underscoring their possible relevance for molecular biotechnology, although representing a still very young field. An introductive section presents the major issues related to theoretical and technical aspects of ESI-MS under non-denaturing conditions. Examples from our work and from the literature illustrate which kind of information can be obtained concerning key issues in biotechnology such as stability and aggregation of proteins under both near-native and challenging conditions, and interactions with other proteins, ligands and cofactors. [source] Single-point mutations at the surface of MB-1Trp lead to important changes in its conformational propertiesCHEMICAL BIOLOGY & DRUG DESIGN, Issue 1 2004M. Sasseville Abstract:, Protein design is currently used for the creation of new proteins with desirable traits. In our lab we focus on the synthesis of proteins with high essential amino acid content having potential applications in animal nutrition. One of the limitations we face in this endeavour is achieving stable proteins despite a highly biased amino acid content. We report here the synthesis and the characterization of three variants of MB-1Trp in which two solvent-exposed Leu have been replaced by Glu allowing for the formation of new salt bridges at the surface of the protein. Although both mutations were expected to be similar (i.e. same mutation in a comparable local environment), they appear to have different effects on MB-1Trp as shown by far-UV circular dichroism, thermal denaturation, fluorescence and proteolytic resistance measurements. For the mutation Leu68Glu, an increase in the protein melting temperature of 6 °C was observed. Surprisingly, the mutation in position Leu19Glu led to a decrease in melting temperature and a modification of tertiary structure. [source] Studies on the conformational properties of CP-1042,55, the hinge region of CP-10, using circular dichroism and RP-HPLCCHEMICAL BIOLOGY & DRUG DESIGN, Issue 6 2000E. Lazoura Abstract: The conformational properties of CP-1042,55, a peptide corresponding to the hinge region of CP-10, were investigated using circular dichroism spectroscopy and reverse-phase high-performance liquid chromatography (RP-HPLC). The circular dichroism studies indicated that CP-1042,55 formed considerable secondary structure in the presence of hydrophobic solution environments including 50% acetonitrile, 50% trifluoroethanol and 200 mm sodium dodecyl sulfate, which comprised a mixture of ,-helix and ,-sheet. The effect of temperature on the conformation of CP-1042,55 was investigated between 5 and 40°C, with very small changes in the spectra being observed.RP-HPLC was then used to investigate the effect of temperature on the conformation of CP-1042,55 in the presence of a hydrophobic surface. Using a C18 -adsorbent, CP-1042,55 exhibited a conformational transition at 25°C, which was associated with an increase in the chromatographic contact area and the binding affinity of the peptide for the stationary phase. In addition, near-planar bandbroadening behaviour indicated that conformational species interconverted with rapid rate constants compared with the chromatographic time scale. These results indicated that the conformational change at 25°C in theRP-HPLC system most likely corresponds to the unfolding of an ,-helical and/or ,-sheet structure to an extended coil structure. Therefore, the strong chemotactic properties of this peptide may be attributed to its ability to form considerable secondary structure in the presence of a hydrophobic environment. [source] ,- O -Linked Glycopeptide Mimetics: Synthesis, Conformation Analysis, and Interactions with Viscumin, a Galactoside-Binding Model LectinCHEMISTRY - A EUROPEAN JOURNAL, Issue 40 2009Jesús Jiménez-Barbero Prof. Abstract Efficient cycloaddition of a silylidene-protected galactal with a suitable heterodiene yielded the basis for a facile diastereoselective route to a glycopeptide-mimetic scaffold. Its carbohydrate part was further extended by ,1,3-linked galactosylation. The pyranose rings retain their 4C1 chair conformation, as shown by molecular modeling and NMR spectroscopy, and the typical exo -anomeric geometry was observed for the disaccharide. The expected bioactivity was ascertained by saturation-transfer-difference NMR spectroscopy by using the galactoside-specific plant toxin viscumin as a model lectin. The experimental part was complemented by molecular docking. The described synthetic route and the strategic combination of computational and experimental techniques to reveal conformational properties and bioactivity establish the prepared ,- O -linked glycopeptide mimetics as promising candidates for further exploitation of this scaffold to give O -glycans for lectin blocking and vaccination. [source] Unexpected Conformational Properties of 1-Trifluoromethyl-1-Silacyclohexane, C5H10SiHCF3: Gas Electron Diffraction, Low-Temperature NMR Spectropic Studies, and Quantum Chemical Calculations,CHEMISTRY - A EUROPEAN JOURNAL, Issue 6 2007Georgiy Abstract The molecular structure of axial and equatorial conformers of 1-trifluoromethyl-1-silacyclohexane, (C5H10SiHCF3), as well as the thermodynamic equilibrium between these species was investigated by means of gas electron diffraction (GED), dynamic nuclear magnetic resonance (DNMR) spectroscopy, and quantum chemical calculations (B3LYP, MP2, and CBS-QB3). According to GED, the compound exists as a mixture of two Cs symmetry conformers possessing the chair conformation of the six-membered ring and differing in the axial or equatorial position of the CF3 group (axial=58(12) mol,%/equatorial=42(12) mol,%) at T=293,K. This result is in a good agreement with the theoretical prediction. This is, however, in sharp contrast to the conformational properties of the cyclohexane analogue. The main structural feature for both conformers is the unusually long exocyclic bond length SiC 1.934(10),Å. A low-temperature 19F,NMR experiment results in an axial/equatorial ratio of 17(2) mol,%:83(2) mol,% at 113,K and a ,G,, of 5.5(2),kcal,mol,1. CBS-QB3 calculations in the gas-phase and solvation effect calculations using the PCM(B3LYP/6-311G*) and IPCM(B3LYP/6-311G*) models were applied to estimate the axial/equatorial ratio in the 100,300,K temperature range, which showed excellent agreement with the experimental results. The minimum energy pathways for the chair-to-chair inversion of trifluoromethylsilacyclohexane and methylsilacyclohexane were also calculated using the STQN(Path) method. [source] Chemoenzymatic synthesis and properties of Schiff bases containing (R)-1-(9-anthryl)ethylamineCHIRALITY, Issue 8 2002Marin Roje Abstract Racemic 1-(9-anthryl)ethylamine (10), obtained in 70% overall yield from commercial 9-cyanoanthracene, was kinetically resolved by the Candida antarctica A lipase-catalyzed acetylation with isopropyl acetate as acyl donor, affording (R)-(+)- 10 with 95.8% enantiomeric excess (e.e.) (E- value 43.5), which afforded Schiff bases (R)- 4 and(R)- 8.1H-NMR, CD, and MM2 calculations offer a consistent picture of the conformational properties of these potential ligands and an explanation for the limited enhancement of enantioselectivity in cyclopropanation of styrene by their Cu(I) complexes, as compared with previously studied ligands in this series. Chirality 14:625,631, 2002. © 2002 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||||||||