bluuebunny/crossref_metadata_2025_split huggingface dataset:
α‐Helical small molecular size analogues of neuropeptide Y: Structure‐activity relationships
Authors: Jung Günther , Beck‐Sickinger Annette G. , Dürr Hansjörg , Gaida Wolfram , Schnorrenberg Gerd 
Published: December 2004

AbstractC‐terminal analogues of neuropeptide Y (NPY) of small molecular size have been synthesized. The influence of chain length, single or multiple amino acid substitution, and segment substitutions on receptor binding, pre‐ and postsynaptic biological activity, and conformational properties have been investigated. Receptor binding and in vivo assays revealed biological activity for NPY Ac‐25‐36 that increased with increasing α‐helicity. In attempts to stabilize the α‐helical content, three independent types of modified NPY Ac‐25‐36 analogues were synthesized. Strong agonistic activities could be detected in a series of discontinuous analogues, which are constructs of N‐terminal parts linked via different spacer molecules to C‐terminal segments. One of the most active molecules was NPY 1‐4‐Aca‐25‐36 (Aca, ε‐aminocaproic acid). For the first time conformational properties of a series of small NPY analogues have been investigated by CD, and correlated with biological activity and receptor binding. A C‐terminal dodecapeptide segment of NPY with an amount of 50% substitution to the native C‐terminal sequence of NPY was found to exhibit significant receptor binding.
Fluorescence, CD, and nmr studies on spantide, a bombesin and substance P antagonist
Authors: Di Bello Carlo , Scatturin Angelo , D'Auria Gabriella , Gargiulo Mario , Paolillo Livio , Trivellone Enrico , De Castiglione Roberto 
Published: December 2004

AbstractThe conformational properties of spantide [(D‐Arg1, D‐Trp7,9, Leu11)substance P] have been studied by fluorescence, CD, and nmr techniques. The fluorescence, CD, and nmr parameters in different solvents and in a micellar environment (SDS) are compared with the data collected for bombesin. A preliminary investigation on [D‐Pro2] spantide is also reported.
Ion binding of cyclolinopeptide A: An nmr and CD conformational study
Authors: Tancredi Teodorico , Benedetti Ettore , Grimaldi Maria , Pedone Carlo , Rossi Filomena , Saviano Michele , Temussi Piero Andrea , Zanotti Giancarlo 
Published: December 2004

AbstractCD and nmr techniques have been used to study, in acetonitrile solution, the ion‐complexing capability of Cyclolinopeptide A (CLA), a cyclic nonapeptide of sequence

endowed with remarkable cytoprotective ability in vitro, and the conformation of the Ba2+/ CLA complex.At room temperature, CLA in acetonitrile shows a proton nmr spectrum characteristic of the coexistence of many different conformers in intermediate exchange. The backbone contains a cis Pro‐Pro bond, with all other peptide bonds in the transconformation.CLA binds Ba2+ more tightly than the other cations studied, namely K+, Na+, Mg2+, and Ca2+; CD data are indicative of the presence of both 1 : 2 (sandwich) and 1 : 1 (equimolar) type complexes, depending on the Ba2+ ion concentration, whereas nmr data are consistent with an equimolar form.The relevant conformational features of the equimolar Ba2+/CLA complex are that the backbone contains all transpeptide bonds, a type I 6 → 3 β‐turn and a 3 → 1 γ‐turn (or a distorted 3 → 9 β‐turn). The global shape of the complexed peptide can be described as a bowl, with the concave (polar) side hosting Ba2+ and the convex side predominantly apolar.
Internal dynamics of linear and superhelical DNA as studied by photon correlation spectroscopy
Authors: Seils J. , Dorfmüller TH. 
Published: December 2004

AbstractPhoton correlation spectroscopy has been used to study the translational (D0)and internal dynamics of monodisperse linear and polydisperse superhelical plasmid‐DNAs. Scattering vector dependent correlation functions were measured and analyzed with the inverse Laplace transform CONTIN written by S. Provencher. For scattering vectors (q) lower than 1.3 × 105cm−1, D0 can be separated from internal dynamics. Using the measured D0value, the q dependence of internal modes was determined. Extrapolation of the internal relaxation times for q → 0 yields the longest internal relaxation time t1. This time can be connected to the persistence length in terms of the Berg‐Soda model, which describes the molecule as a semiflexible circular polymer with hydrodynamic interactions. The calculated length of 76 nm for DNA, I = 0.15 mol/L, is a little higher than the one obtained from static light scattering data without excluded volume corrections. A comparison of experimental and simulated correlation functions for the Berg‐Soda model shows that the model gives a fairly good description of the dynamics of the linear molecule, whereas large discrepancies between model and experimental functions are observed for the superhelical DNA. Small differences between model and experimental functions are mainly attributed to the neglect of the torsional modes that may be coupled to bending and flexing modes. For the superhelical DNA the agreement is improved if the calculation is carried out with a linear molecule, with shorter contour length and increased diameter. Both quantities can be derived from the known superhelix tilt angle.
Investigation of zinc‐binding affinities of moloney murine leukemia virus nucleocapsid protein and its related zinc finger and modified peptides
Authors: Mely Yves , Cornllle Fabrice , Fournié‐Zaluski Marie‐Claude , Darlix Jean‐Luc , Roques Bernard F. , Gérard Dominique 
Published: December 2004

AbstractNucleocapsid proteins of retroviruses are small basic, nucleic acid‐binding proteins with either one or two “Cys‐His” boxes, which have been shown to be involved in genomic RNA dimerization, encapsidation, and replication primer tRNA annealing to the initiation site for reverse transcription. The nucleocapsid (NC) protein of Moloney murine leukemia virus (MoMuLV NCp10) is made up of 56 residues with one Cys‐His motif. The Zn2+‐binding affinities and induced conformational changes of NCp10 were investigated by following the fluorescence of Trp 35 located in the Cys‐His domain. At pH 7.5, NCp10 was shown to bind Zn2+ at a 1 : 1 ratio with a very high apparent binding constant of 1.2 (±0.3) · 1013M−1. A similar apparent binding constant was obtained for a 19‐residue peptide encompassing the Cys‐His box, designated the “zinc finger motif,” indicating that it contains most if not all the information to bind Zn2+ tightly. Changing Trp 35 to Phe in the peptide did not affect the Zn2+ affinity, indicating that Trp 35 is not crucial for Zn2+ binding. On the contrary‐, replacing Cys 29 by Ser, the chemical modification or oxidation of the three Cys sharply reduced Zn2+ affinity, confirming the essential role of Cys in Zn2+ binding. In addition, fluorescence and energy transfer data suggested that Zn2+ binding modifies the Trp 35 environment but not its solvent exposure, and increases the average distance between Tyr 28 and Trp 35 by about 2 Å. These data suggest that Zn2+ binding to retroviral NC protein is biologically relevant.
Effects of limited input distance constraints upon the distance geometry algorithm
Authors: Oshiro C. M. , Thomason John , Kuntz I. D. 
Published: December 2004

AbstractIn this paper we examine the distance geometry (DG) algorithm in the form used to determine the structure of proteins. We focus on three aspects of the algorithm: bound smoothing with the triangle inequality, the random selection of distances within the bounds, and the number of distances needed to specify a structure. Computational experiments are performed using simulated and real data for basic pancreatic trypsin inhibitor (BPTI) from nmr and crystallographic measurements. We find that the upper bounds determined by bound smoothing to be a linear function of the true crystal distance. A simple model that describes the results obtained with randomly selected trial distances is proposed. Using this representation of the trial distances, we show that BPTI DG structures are more compact than the true crystal structure. We also show that the DG‐generated structures no longer resemble test structures when the number of these interresidue distance constraints is less than the number of degrees of freedom of the protein backbone. While the actual model will be sensitive the way distances are chosen, our conclusions are likely to apply to other versions of the DG algorithm.
Intercalation binding of 6‐substituted naphthothiopheneamides to DNA: Enthalpy and entropy components
Authors: Hopkins Harry P. , Ming Yang , Wilson W. David , Boykin David W. 
Published: December 2004

AbstractN‐(3‐dimethylaminopropyl) naphtho [2, 1‐b] thiophene‐4‐carboxamide and the 6‐substituted methoxy, methyl, fluoro, chloro, bromo, trifluoromethyl, and cyano derivatives have been shown to bind to DNA via intercalation with binding constants in the 35–900 × 103 range at 25°C, pH 7, and [Na+] = 0.019M . Both electron‐donating and ‐withdrawing substituents enhance intercalation binding, but the binding affinity is most enhanced by the cyano substituent. Calorimetric titrations for calf thymus DNA differ dramatically from those reported for ethidium [Hopkins et al. (1990) Biopolymers Vol. 29, pp. 449–459]. Apparent enthalpy parameters (ΔHB) for intercalation are constant only at low coverage of sites and become much more positive as saturation is approached. In the plateau region, ΔHB values for the parent and the cyano‐, fluoro‐, chloro‐, and bromo‐substituted compounds are nearly the same (∼ −5.9 kcal/mol). For the methyl‐ (−6.8 kcal/mol) and methoxy‐ (−7.5 kcal/mol) substituted compounds, the ΔHB values are more exothermic than that for the un‐substituted compound, whereas ΔHB for the trifluoromethyl compound is approximately 1 kcal/mol less exothermic. The corresponding ΔSB values, corrected for mixing effects, are in the 7–15‐cal/deg/mol range and are approximately linearly related to ΔHB if the cyano derivative is excluded.
Electrostatic interactions in protein solution—a comparison between poisson–boltzmann and Monte Carlo calculations
Authors: Fushiki M. , Svensson B. , Jönsson Bo , Woodward C. E. 
Published: December 2004

AbstractThe accuracy of the Poisson–Boltzmann (PB) approximation and its linearized version is investigated by comparison to results obtained from Monte Carlo simulations. The dependence of the calcium binding constant of the protein calbindin as a function of salt concentration and mutation is used as a test case. The protein is modeled as a collection of charged and neutral spheres immersed in the electrolyte solution. The PB equation is solved using a finite difference technique on a grid in a spherical polar coordinate system, which is the preferred choice for a globular protein like calbindin. Both MC and PB give quantitative agreement with experimental results. The linearized PB equation is almost as accurate, but it becomes less reliable in systems with divalent ions. However, the linearized PB equation fails to describe the concentration profiles for cations and anions outside the protein even in a 1 : 1 salt solution.
Conformational analysis of a IgG1 hinge peptide derivative in solution determined by NMR spectroscopy and refined by restrained molecular dynamics simulations
Authors: Kessler Horst , Mronga Siggi , Müller Gerhard , Moroder Luis , Huber Robert 
Published: December 2004

AbstractThe hinge region links the antigen binding Fab part to the constant Fc domain in immunoglobulins. For the hinge peptide derivative [AcThr(OtBu)‐Cys‐Pro‐Pro‐Cys‐Pro‐Ala‐ProNH2]2 the assignment of the 1H and 13C resonances was achieved by two‐dimensional nmr techniques: total correlation spectroscopy (TOCSY), nuclear Ovethauser enhancement spectroscopy (NOESY), rotating frame nuclear Overhauser enhancement spectroscopy (ROESY), heteronuclear multiple quantum coherence (HMQC) transfer, and a HSQC (modified Overbodenhausen experiment) with high resolution in F1, which was several times folded in F1 but still phase correctable. Conformational relevant parameters (78 nuclear Overhauser effect distance restraints, 3JHH for prochiral assignments, temperature gradients) were determined by nmr and served as input data for molecular dynamics (MD) structure refinement. A simulated model compound corresponding to the [Cys‐Pro‐Pro‐Cys]2 core elongated by the peptide chains in the Fab and Fc direction served as a starting structure for the final MD run. The conformation calculated in in vacuo does not agree with the C2 symmetry required from nmr data, but the structure obtained by a water simulation fulfills the requirement. Here the core of the hinge peptide derivative adopts a polyproline II double helix as in the x‐ray structure of IgG1. Hence, segments responsible for the internal flexibility are located outside the core as confirmed by the flexibility of the solvent exposed C termini.
Comparison of the bis‐intercalating complexes formed between either ditercalinium or a flexible analogue and d(CpGpCpG)2 or d(TpTpCpGpCpGpApA)2 minihelices: 1H‐ and 31P‐nmr analyses
Authors: Pothier Joël , Delepierre Muriel , Barsi Marie‐Christine , Garbay‐Jaureguiberry Christiane , Igolen Jean , Le Bret Marc , Roques Bernard P. 
Published: December 2004

AbstractThe 400‐MHz 1H‐ and 162‐MHz 31F‐nmr have been used to study complexes constituted by (a) the d(TpTpCpGpCpGpApA)2 or the d(CpGpCpG)2 self‐complementary oligonucleotides and (b) two bifunctional 7H‐pyrido [4, 3‐c] carbazole dimer drugs, the antitumoral ditercalinium (NSC 366241), a dimer with a rigid bis‐piperidine linking chain and its pharmacologically inactive analogue, a dimer with a flexible spermine‐like linking chain. Nearly all proton and phosphorus signals have been assigned by two‐dimensional (2D) nmr (correlated spectroscopy, homonuclear Hartmann‐Hahn, nuclear Overhauser enhancement spectroscopy, 2D 31P {1H} heteronuclear correlated spectroscopy and 31P‐31P chemical exchange experiments). Both drugs bis‐intercalate into the two CpG sites. The complexes show small differences in the position of the 7H‐pyrido[4, 3‐c]carbazole ring into the intercalation site and possibly in the ribose‐phosphate backbone deformation. However, the inactive analogue exhibits a longer residence lifetime in octanucleotide than the ditercalinium does. All these results are discussed in terms of differences in dimer activities.
Resolution of end‐to‐end diffusion coefficients and distance distributions of flexible molecules using fluorescent donor‐acceptor and donor‐quencher pairs
Authors: Lakowicz Joseph R. , Kuśba Józef , Szmacinski Henryk , Gryczynski Ignacy , Eis Peggy S. , Wiczk Wieslaw , Johnson Michael L. 
Published: December 2004

AbstractWe used time‐dependent fluorescence energy transfer, time–dependent collisional quenching, and global analysis of the data resulting from these through–space and contact interactions to recover the end–to–end distance distributions and diffusion coefficients of flexible fluorescent molecules. The fluorescence decays of covalently linked tryptamine–acceptor and tryptamine–quencher pairs were measured by the frequency–domain method. These data were fit using numerical solutions of the differential equation, which predicts the time–and distance–dependent population of the excited state donors in the presence of energy transfer or collisional quenching, followed by transformation to the frequency domain for nonlinear least–squares comparison with the experimental data. We found that the energy transfer data for the donor–acceptor pair alone were adequate to recover the starting distribution and the end–to–end diffusion coefficient; however, the resolution is dramatically improved by the use of both the through–space and contact interactions.
Kinetics of folding and unfolding of αα‐tropomyosin and of nonpolymerizable αα‐tropomyosin
Authors: Mo Jianming , Holtzer Marilyn Emerson , Holtzer Alfred 
Published: December 2004

AbstractStopped flow CD (SFCD) kinetic studies of self–assembly of coiled coils of rabbit αα–tropomyosin and of nonpolymerizable αα–tropomyosin (NPTm) are reported. The protein was denatured in 6M urea buffer, then renatured by 10‐fold dilution into benign saline buffer. Folding was monitored by SFCD in the backbone region (222 nm). Protein chains are shown to be totally unfolded (and separated in the reduced species) in the initial denaturing medium and fully folded as two‐chain coiled coils in the final benign medium. In all cases of folding in benign buffer of totally unfolded chains, two phases were found in the folding process: a fast phase (<0.04 s, the SFCD dead time), in which an intermediate state with about 70% of the equilibrium ellipticity forms; followed by a slower, observable phase that completes the folding. The slow phase is first order (k −1 = 1.6 s at 20°C), signifying that chain association for reduced samples occurs in the fast phase. In contrast, folding in benign buffer from an initial state with 70% of the equilibrium ellipticity is all fast, suggesting that the folding intermediate is not an equilibrium species. Cross‐linking at Cys‐190 increases the helix content of the fast‐formed intermediate state to about 85% of the equilibrium value, but leaves the rate constant of the slow phase unchanged. In NPTm, which does not form high aggregates at low ionic strength, the rate of the observable phase is almost independent of ionic strength in the range of ∼ 0.15‐0.6M, but is reduced one to two orders of magnitude by further reduction to 0.026M. In folding from totally unfolded chains, the rate is reduced less than one order of magnitude by changing the final state to about 50% folded. In contrast to folding, unfolding of αα‐tropomyosin from the native state is all fast.
Photodegradation of hyaluronic acid: EPR and size exclusion chromatography study
Authors: Lapc̆ík L'. , Chabrec̆ek P. , Stas̆ko A. 
Published: December 2004

AbstractPhotochemically induced radical reactions involving the lateral sequences and the end macromolecular chain groups of hyaluronic acid in aqueous solutions at 293K were studied by EPR spin trapping technique with DMPO (5,5‐dimethylpyrroline‐1‐oxide). In the first 1‐10 minutes of irradiation EPR indicates spin adducts of two carbon centered radicals with the splitting constants of aN = 1.60 mT, aH = 2.51 mT and aN = 1.56 mT, aH = 2.28 mT. After longer irradiation time (over 10 minutes) dominate two further DMPO adducts of radicals centered on hetero–atoms with splitting constants of aN = 1.44 mT, an = 1.60 mT and of aN = 1‐49 mT, aH = 1.49 mT. Simultaneously, molecular weight followed by SEC decreases, suggesting that UV irradiation leads to the breaking of interglycosidic bonds of hyaluronic acid main macromolecular chain.
Development of an extended simulated annealing method: Application to the modeling of complementary determining regions of immunoglobulins
Authors: Higo Junichi , Collura Vincent , Garnier Jean 
Published: December 2004

AbstractAn extended simulated annealing process (ESAP) has been developed in order to obtain an ensemble of conformations of a peptide segment from a protein fluctuating at a given temperature. The annealing process was performed with a fast Monte Carlo method using the scaled collective variables developed by Noguti and Gō. The system was divided into two parts: one consists of one or more peptide segments and is flexible around the main‐chain and side‐chain torsional angles; the other represents the rest of the molecule and was maintained fixed at the atomic positions determined by x‐ray experiments. The target function included the nonbonding atomic interactions and a distance function to anchor the N and C terminal ends of each segment to the fixed part. Three systems of complementary determining regions (CDR) of antibodies were tested and compared to x‐ray data: L2 loop (7 residues) of the light chain of α‐type Bence‐Jones protein, H1 and the H2 loops (14 residues) of McPC603, and H1 and H2 loops (12 residues) of HyHEL‐5. Each state of CDR conformations was characterized at room temperature by the average of their coordinates (average conformation) and the internal energy. With a limited number of annealing processes (10), starting from the extended conformation, we have obtained states with conformations close to the observed x‐ray structures, from 1.1 to 1.7 Å root mean square deviation (rmsd) of main‐chain atoms depending on the system. These states were identical or within 0.25 Å rmsd of those of lowest internal energy. For unknown CDR structures the criteria of lowest internal energies from ESAP can be used to predict hypervariable loop structures in antibodies with an accuracy comparable to other methods.
A sequence‐dependent 1H‐NMR study on the formation of β‐turns in tetrapeptides containing charged residues
Authors: Liu Xiaohong , Scott Paul G. , Otter Albin , Kotovych George 
Published: December 2004

AbstractThe importance of side‐chain charge interactions in the formation of β‐turns was studied. Sixteen protected NAc‐tetrapeptide amides were studied, namely the variants of DEKS: NEKS, EEKS, DDKS, DQKS, NQKS, DERS, NERS, EERS, DDRS, NDRS, DQRS, and DKES. Three tetrapeptides—NPDM, NSDM, and NDDS—were also studied as they have a high probability of forming β‐turns, based on statistical predictions. The results indicate that a small proportion of type I β‐turn exists in solutions of DEKS and DERS in methanol/ water (60/40), while NEKS has an even smaller population of this turn. The other tetrapeptides are present in solution only in the extended conformation. These results clearly show the importance of the salt bridge between the side chains of K2 and E3 or R2 and E3, as well as the importance of the charge on the side chain of the first residue in stabilizing the β‐turn. The relevance of statistical predictions for β‐turns in short peptides is discussed.
The electrostatic contribution to DNA base‐stacking interactions
Authors: Friedman Richard A. , Honig Barry 
Published: December 2004

AbstractBase‐stacking and phosphate‐phosphate interactions in B‐DNA are studied using the finite difference Poisson–Boltzmann equation. Interaction energies and dielectric constants are calculated and compared to the predictions of simple dielectric models. No extant simple dielectric model adequately describes phosphate–phosphate interactions. Electrostatic effects contribute negligibly to the sequence and conformational dependence of base‐stacking interactions. Electrostatic base‐stacking interactions can be adequately modeled using the Hingerty screening function. The repulsive and dispersive Lennard–Jones interactions dominate the dependence of the stacking interactions on roll, tilt, twist, and propeller. The Lennard–Jones stacking energy in ideal B‐DNA is found to be essentially independent of sequence.
Characterization at atomic resolution of peptide helical structures
Authors: Benedetti E. , Di Blasio B. , Pavone V. , Pedone C. , Toniolo C. , Crisma M. 
Published: December 2004

AbstractA survey of literature for the various types of helices experimentally observed in highresolution single crystal x‐ray diffraction analyses of peptides has allowed to determine accurate conformational and helical parameters for the various secondary structures such as the α‐helix, the 310‐helix, the fully extended conformation (25‐helix) and the β‐bend ribbon spiral. For each of these structures the characteristic ϕ, ψ conformational parameters, n, the number of residues per turn, h, the height per residues and p, the pitch of the helix are described.