bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnetic circular dichroism study on synthetic polynucleotides, bacteriophage structure, and DNA's
Authors: Maestre Marcos F. , Gray Donald M. , Cook Randall B.
Published: December 2004

The MCD (magnetic circular dichroism) spectra of Ap, ApA, ApApA, poly A, Up, UpU, poly U and double‐stranded poly A:U alternating copoly A–U and alternating deoxyribopoly A–T were measured with a Cary 61 spectropolarimeter fitted with a Varian superconducting magnet at a field strength of 50 Kgauss. The MCD spectra of T2 and T5 DNA at various stages of heal denaturation were measured as a function of hyperchromicity of the sample. MCD spectra of the intact and degraded T2 and T5 phages were used to study the degree of alteration of the DNA inside the phages versus the DNA in vitro. The results for the adenine polymers show that the main MCD bands, B2u(271 nm), B1u(252 nm), and E1u(212 nm), show a decrease in specific magnitude as the length of the polymer is increased, reflecting the degree of stacking of the polymer. In contrast, the uridine series of polymers shows little change of the MCD bands, indicating that there is little interaction between the bases regardless of the length of the polymers. The MCD spectra of poly A:U, alternating poly r(A–U): (A–U), and alternating poly d(A–T):(A–T) show significant differences among themselves in the magnitude of the B2u band and when compared with the sum of the spectrum for the poly A plus poly U. This may indicate the selective effect of hydrogen bonding on the B2u band. Alternatively, the difference may be due to the absence of an n → π* transition in the double‐stranded polymer. Measurements of denatured T2 and To DNA's show increases in all MCD bands. The T2 DNA internally packed in phage shows an increase of the B2u and E1ubands, the B2u remaining unchanged. The internal T5 DNA shows an increase of the B1u band only. Thus, the internal DNA structure is altered in a manner quite different from a simple denaturation caused by hydrogen bond breaking. Furthermore, different MCD bands indicate that different modes of DNA packing exist for T2 and T5 phages.
An infrared study of unordered poly‐L‐proline in CaCL2 solutions
Authors: Johnston Nancy , Krimm S.
Published: December 2004

Infrared spectra have been obtained of poly‐L‐proline in aqueous CaCl2 solutions. As the salt concentration is increased, the CO stretching band develops a component at the frequency found in the solid state while the CH2 bending band broadens to higher frequency. Since circular dichroism spectra indicate progressive disordering of the chain with increasing salt concentration, we associate the infrared spectral changes with the same phenomenon. Our interpretation of these changes, particularly in the CH2 bending modes, is that disordering is associated primarily with an increase in the range of accessible Cα–C′ (O) rotation angles rather than with the random introduction of cis imide bonds in the chain.
Evaluation of RNA conformation from circular dichroism and optical rotatory dispersion data
Authors: Gratzer W. B. , Richards E. G.
Published: December 2004

An analysis of optical rotatory dispersion and circular dichroism of RNA is described which leads to an estimate of the degree of base pairing. By the use of new standards for the double‐helical parts of the molecule, based on data for two‐stranded viral RNA species, a good fit between calculated and observed curves can be achieved. Where data are available the results of analyses of optical rotatory dispersion and circular dichroism in general show satisfactory consistency.
Fourier transform ir spectroscopy of collagen and gelatin solutions: Deconvolution of the amide I band for conformational studies
Authors: Payne K. J. , Veis A.
Published: December 2004

The ir spectra of lathyritic rat skin collagen and calf skin gelatin solutions at a variety of temperatures were obtained using Fourier transform ir spectroscopy and a 9‐reflection, 2‐pass ZnSe prism sample cell. The spectra were then deconvolved (based on Kauppinnen's method) and the behavior of the amide I band at ∼ 1650 cm−1 observed in detail. Throughout the temperature range studied (4–50°C), three component absorption peaks within the amide I band (at 1633, 1643, and 1660 cm−1) are common to the spectra irrespective of the degree of triple helix content of the sample. Changes in the relative intensities of these component peaks are, however, conformationally dependent. During denaturation of the triple helix, the dominant 1660‐cm−1 component in the native collagen spectrum diminishes and the 1633‐cm−1 peak becomes relatively intensified. The inherently strong basicity of the carbonyl group of the proline residues together with the frequent occurrence of this imino acid in the X position of the Gly‐X‐Y triplet of collagen largely accounts for the −30‐cm−1 shift of the amide I band during denaturation. Temperature and conformationally dependent changes in the fine structure of the amide I band from dilute solutions of collagen can be monitored in a reproducible and quantitative fashion.
Thermodynamics of cyclophilin catalyzed peptidyl‐prolyl isomerization by nmr spectroscopy
Authors: Videen John S. , Stamnes Mark A. , Hsu Victor L. , Goodman Murray
Published: December 2004

One‐dimensional nmr exchange spectroscopy was carried out to determine thermodynamic parameters of cyclophilin‐induced cis‐trans isomerization of succinyl‐Ala‐Phe‐Pro‐Phe‐p‐nitroanilide. Rate measurements were possible at physiological temperatures. The kc/Km of rat cyclophilin was found to he 12.8 (±0.5) s−1 μM−1 at 37°C, intermediate to previously reported values that used a coupled enzyme assay extrapolated to this temperature. Activation energies (ΔG≠) for the uncatalyzed and catalyzed reaction at 37°C were found to be 19.7 and 17.1 kcal/mol, respectively, and were primarily due to an enthalpic barrier. © 1994 John Wiley & Sons, Inc.
Monte Carlo and Poisson–Boltzmann calculations of the fraction of counterions bound to DNA
Authors: Lamm Gene , Wong Linda , Pack George R.
Published: December 2004

The counterion density and the condensation region around DNA have been examined as functions of both ion size and added‐salt concentration using Metropolis Monte Carlo (MC) and Poisson–Boltzmann (PB) methods. Two different definitions of the “bound” and “free” components of the electrolyte ion atmosphere were used to compare these approaches. First, calculation of the ion density in different spatial regions around the polyelectrolyte molecule indicates, in agreement with previous work, that the PB equation does not predict an invariance of the surface concentration of counterions as electrolyte is added to the system. Further, the PB equation underestimates the counterion concentration at the DNA surface, compared to the MC results, the difference being greatest in the grooves, where ionic concentrations are highest. If counterions within a fixed radius of the helical axis are considered to be bound, then the fraction of polyelectrolyte charge neutralized by counterions would be predicted to increase as the bulk electrolyte concentration increases.

A second categorization—one in which monovalent cations in regions where the average electrostatic potential is ledd than −kT are considered to be bound—provides an informative basis for comparison of MC and PB with each other and with counterion‐condensation theory. By this criterion, PB calculations on the B from of DNA indicate that the amount of bound counterion charge per phosphate group is about .67 and is independent of salt concentration. A particularly provocative observatiob is that when this binding criterion is used, MC calculations quantitatively reproduce the bound fraction predicated by counterion‐condensation theory for all‐atom models of B‐DNA and A‐DNA as well as for charged cylindera of varying lineat charge densities. For example, for B‐DNA and A‐DNA, the fractions of phosphate groups neutralized by 2 Å hard sphere counterions are 0.768 and .817, respectively. For theoretical studies, the rediys enclosing the region in which the electrostatic potential is calculated studies, the radius enclosing the region in which the electrostatic potential is calculated to be less than −kT is advocated s a more suitable binding or condensation radius that enclosing the fraction of counterions given by (1 – ξ−1). A comparsion of radii calculated using both of these definitions is presented. © 1994 John Wiley & Sons, Inc.
Does Flory–Huggins theory help in interpreting solute partitioning experiments?
Authors: Holtzer Alfred
Published: December 2004

The development of Flory–Huggins (FH) theory is reviewed, particularly with regard to the molecular significance of the interaction parameter that scales the contact interaction of solute and solvent. The chemical potential given by FH theory for an “idealute” solute is then compared with that provided by a more general, statistical thermodynamic approach. It is found that the FH contact term does not directly correspond to the solvation free energy. The significance of this result for the interpretation of free energies of transfer of a solute from one solvent to another is examined. It is shown that neither the earlier recommended standard free energy change for the process (using the infinitely dilute reference state, mole fraction units) nor the recently recommended FH‐corrected standard free energy change provides the solvation energy desired. Instead, the standard free energy using the infinitely dilute reference state and molarity units, as long advocated by Ben‐Naim, provides the desired solvation free energy. Correction of extant values, based on mole fraction units, is easily made. However, application of such results to problems of protein folding is not straightforward. © 1994 John Wiley & Sons, Inc.
Microcalorimetric investigations of the interactions of small ions with arterial elastin
Authors: Winlove C. Peter , Parker Kim H.
Published: December 2004

The enthalpies of interactions of porcine arterial elastin with alkali metal and alkali earth halides and sulphates were investigated by means of flow microcalorimetry and the stoichiometry measured using radiotracer techniques. In aqueous solutions, all alkali earth halides interacted exothermically at concentrations ranging from 0.01 to 2.5M. All the alkali metal halides, particularly NaCl, exhibited complex concentration‐dependent interactions, exothermic at low concentrations and endothermic at high concentrations. Both the anion and cation contributed to the response, although the anion seemed to dominate. SO interacted most strongly of the anions tested. All interactions were reversible in the sense that repeat experiments gave identical results, but the enthalpy of “adsorption” was generally different from that of “desorption.” The enthalpy of interaction depended on the conformation of the elastin in a salt‐specific manner. For example, CaCl2 and MgCl2 interacted similarly in water but very differently in 1 : 1 water : methanol. © 1994 John Wiley & Sons, Inc.
Phosphophoryn, a biomineralization template protein: pH‐dependent protein folding experiments
Authors: Evans John Spencer , Chan Sunney I.
Published: December 2004

The protein folding behavior of a polyelectrolyte protein, bovine dentine phosphophoryn (BDPP), in the pH range of 1.82–11.0 has been investigated. One‐ and two‐dimensional nmr spectroscopy has been utilized to obtain proton spin assignments for amino acid residues in D2O and in H2O. One‐dimensional 31P‐nmr experiments verify the existence of three separate classes of O‐phosphoserine (PSer) resonances in BDPP (α, β, χ), representing three distinct PSer residue populations at pH 6.94. By means of pH titration and 1H‐nmr, five populations of Asp residues can be identified. Three of these populations exhibit secondary inflection points on their pH titration curves that correspond to an observed pKa of 6.17–6.95. The presence or absence of secondary inflection points for Asp populations and the 31P‐nmr chemical shift dispersion for the three PSer residue populations indicate that BDPP may be comprised of homologous (Asp‐Asp)n. (PSer‐PSer)n, and heterologous (PSer‐Asp)n sequences arranged into polyelectrolyte cluster regions.

The pH titration also revealed that certain populations of Ser, Gly, and Pro residues in BDPP exhibit pH‐dependent resonance frequency shifts. The “apparent” pK, for the transition points of these frequency shifts corresponds to either the pK of Pser monophosphatc ester and/or the pKa of Asp COOH group of BDPP polyelectrolyte regions. On the basis of these transition points, we can assign four types of Ser, Gly, or Pro‐containing “intervening” regions in BDPP, based on their sensitivity to protonation and deprotonation events occurring at (Asp)n, (PSer)n, or (PSer‐Asp)n anionic cluster regions that flank the intervening regions.

Our 1H‐ninr experiments also reveal that BDPP assumes a folded conformation at low pH. As the pH increases, this conformation undergoes several unfolding transitions as the BDPP molecule assumes more open conformations in response to increased electrostatic repulsion between polyelectrolyte anionic regions in the protein. These folding‐unfolding transitions are mediated by the intervening regions, which act as “hinges” to allow the polyelectrolyte regions to fold relative to one another. © 1994 John Wiley & Sons, Inc.
Dependence on the dielectric model and pH in a synthetic helical peptide studied by Monte Carlo simulated annealing
Authors: Okamoto Yuko
Published: December 2004

Monte Carlo simulated annealing is applied to the tertiary structure prediction of a 17‐residue synthetic peptide, which is known by experiment to exhibit high helical content at low pH. Two dielectric models are considered: sigmoidal distance‐dependent dielectric function and a constant dielectric function (ϵ = 2). Starting from completely random initial conformations, our simulations for both dielectric models at low pH gave many helical conformations. The obtained low‐energy conformations are compared with the nuclear Overhauser effect spectroscopy cross‐peak data for both main chain and side chains, and it is shown that the results for the sigmoidal dielectric function are in remarkable agreement with the experimental data. The results predict the existence of two disjoint helices around residues 5–9 and 11–16, while nmr experiments imply significant α‐helix content between residues 5 and 14. Simulations with high pH, on the other hand, hardly gave a helical conformation, which is also in accord with the experiment. These findings indicate that when side chains are charged, electrostatic interactions due to these charges play a major role in the helix stability. Our results are compared with the previous 500 ps molecular dynamics simulations of the same peptide. It is argued that simulated annealing is superior to molecular dynamics in two respects: (1) direct folding of α‐helix from completely random initial conformations is possible for the former, whereas only unfolding of an α‐helix can be studied by the latter; (2) while both methods predict high helix content for low pH, the results for high pH agree with experiment (low helix content) only for the former method. © 1994 John Wiley & Sons, Inc.
Partial molar volumes, expansibilities, and compressibilities of oligoglycines in aqueous solutions at 18–55°C
Authors: Chalikian Tigran V. , Sarvazyan Armen P. , Funck Theodor , Breslauer Kenneth J.
Published: December 2004

We have determined the partial molar volumes, expansibilities, and adiabatic compressibilities of glycine, diglycine, triglycine, tetraglycine, and pentaglycine over the temperature range 18–55°C. These data were analyzed and interpreted in terms of the hydration of these short oligoglycines and their constituent groups. From our results, we have estimated the contributions of the peptide group to the partial molar volume and the partial molar adiabatic compressibility of these oligoglycines. Based on these data, we propose that each of the polar atomic groups of the peptide bond forms approximately two hydrogen bonds with adjacent water molecules. Furthermore, the temperature dependence of the partial molar volume suggests that water that solvates the polar groups of a peptide linkage behaves more like a “normal” liquid than does bulk water, which exhibits its well‐known anomalous liquid properties. © 1994 John Wiley & Sons, Inc.
Nmr and molecular modeling investigations of the neuropeptide bradykinin in three different solvent systems: DMSO, 9 : 1 dioxane/water, and in the presence of 7.4 mM lyso phosphatidylcholine micelles
Authors: Young John K. , Hicks Rickey P.
Published: December 2004

The linear nonapeptide hormone bradykinin (Arg1‐Pro2‐Pro3‐Gly4‐Phe5‐Ser6‐Pro7‐Phe8‐Arg9) is involved, either directly or indirectly, in a wide variety of physiological processes, particularly pain and hyperanalgesia. Additional evidence suggests that bradykinin also plays a major role in inflammatory response, asthma, sepsis, and symptoms associated with the rhinoviral infection. It has long been speculated that a β‐turn at the C‐terminus of bradykinin plays a major role in the biological activity of the neuropeptide. The β‐turn forming potential of bradykinin in three vastly different local chemical environments, DMSO, 9 : 1 dioxane/water, and in the presence of 7.4 mM lyso phosphatidylcholine micelles, was investigated using two‐dimensional homonuclear nmr experiments coupled with simulated annealing calculations. The results of these investigations show that in all three systems residues 6–9 of the C‐terminus adopt very similar β‐turn like structures. These results suggest that the β‐turn at the C‐terminus of bradykinin is an important secondary structural feature for receptor recognition and binding. © 1994 John Wiley & Sons, Inc.
Helix formation by the phospholipase A2 38–59 fragment: Influence of chain shortening and dimerization monitored by nmr chemical shifts
Authors: Jiménez M. Angeles , Carreño Cristina , Andreu David , Blanco Francisco J. , Herranz José , Rico Manuel , Nieto José L.
Published: December 2004

The solution structure of a peptide fragment corresponding to the 38–59 region of porcine phospholipase A2 has been investigated using CD, nmr chemical shifts, and nuclear over‐hauser effects (NOEs). This isolated fragment of phospholipase forms an α‐helix spanning residues 38–55, very similar to the one found in the native protein, except for residues 56–58, which were helical in the crystal but found random in solution. Addition of triflouro‐ethanol (TFE) merely increased helix population but it did not redefine helix limits. To investigate how the folding information, in particular that concerning eventual helix start and stop signals, was coded in this particular amino acid sequence, the helices formed by synthetic peptides reproducing sections of this phospholipase 38–59 fragment, namely 40–59, 42–59, 38–50, and 45–57, were characterized using NOEs and helix populations quantitatively evaluated on different peptide chain segments using nmr chemical shifts in two solvents (H2O and 30% TFE/H2O). A set of nmr spectra was also recorded and assigned under denaturing conditions (6Murea) to obtain reliable values for the chemical shifts of each peptide in the random state. Based on chemical shift data, it was concluded that the helix formed by the phospholipase 38–59 fragment was not abruptly, but progressively, destabilized all along its length by successive elimination of residues at the N end, while the removal of residues at the C end affected helix stability more locally and to a lesser extent. These results are consistent with the idea that there are not single residues responsible for helix initiation or helix stability, and they also evidence an asymmetry for contributions to helix stability by residues located at the two chain ends. The restriction of molecular mobility caused by linking with a disulphide bridge at Cys 51 two identical 38–59 peptide chains did not increase helix stability. The helix formed by the covalently formed homodimer was very similar in length and population to that formed by the monomer. © 1994 John Wiley & Sons, Inc.
Site‐Specific thermodynamics of ising networks: A theorem for linearly connected subsystems
Authors: Di Cera Enrico , Keating Sean
Published: December 2004

An Ising network consists of a set of N units existing in two possible states, 0 and 1. If two units contact each other in the network, there is a nearest neighbor interaction that depends only on the states of the units. If an Ising network can be split into two independent subsystems by deleting the contact between two units, then these units specify each other's site‐specific properties and the state of either unit uniquely specifies the state of the other. This theorem holds regardless of (a) the dimensional embedding of the network as a whole, (b) the precise interaction geometry among the units within either subsystem, and (c) the intrinsic energy for the 0 → 1 switching of any given unit. Either subsystem in the network can be considered as a probe for the state of the unit in the other subsystem to which the probe is connected. Application of the theorem to the analysis of the site‐specific properties of the biologically relevant case of a linear network, or heteropolymer, yields a rather counterintuitive result. Knowledge of the state of the end unit in the network, as a function of the change in the thermodynamic driving force for the 0 → 1 transition, is sufficient to completely resolve the energetics of the network. © 1994 John Wiley & Sons, Inc.
Copper ion complex formation of polypeptide containing side‐chain pyridyl groups
Authors: Nagata Yoshitomo , Kanuka Satoru , Kinoshita Takatoshi , Takizawa Akira , Tsujita Yoshiharu , Yoshimizu Hiroaki
Published: December 2004

The complex formation behaviors of an α‐helical polypeptide containing pyridyl ligands in the side chains, poly (Nω‐2‐pyridylmethyl L‐glutamine) (P2PG), were investigated by absorption and CD spectroscopy using Cu2+ ion as a guest molecule in 2,2,2‐trifiuoroethanol solution. In the low Cu2+ ion concentration, P2PG exhibited the predominant formation of Cu2+ and two pyridyl side‐chain complexes, involving a regular arrangement of the pyridyl side chains. On the other hand, the complexes were converted to Cu2+ and one pyridyl side‐chain species with increasing Cu2+ ion concentration. The conversion was accompanied by the disappearance of the side‐chain ordered structure without any changes in the backbone conformation. Moreover, the still remaining coordination sites of Cu2+ were capable of complexing monomer pyridine (Py) added as a second guest to form ternary complexes, P2PG‐Cu2+‐Py, following the reconstitution of the ordered structure on the periphery of the α‐helix backbone. The unique characteristics of P2PG can be explained in terms of the restriction of the pyridyl side chains to form intramolecular chelate complexes, depending on the rigid α‐helix conformation. © 1994 John Wiley & Sons, Inc.
Sol–Gel transition of alginate solution by the addition of various divalent cations: A rheological study
Authors: Wang Zheng‐Yu , Zhang Qing‐Zhi , Konno Mikio , Saito Shozaburo
Published: December 2004

Several rheological properties of aqueous alginate solution have been investigated in the absence and presence of four divalent cations: Ca, Cu, Mn, and Co. The concentration dependence of viscosity in alginate solution without addition of divalent cations shows a similar behavior to that found for other polysaccharides and synthetic polymers. We have found that for Ca(II) ‐added systems, sol‐gel transition curves for different alginate concentrations can be superimposed over the concentration range of this study by using a normalized parameter. Shear‐thinning behavior has been observed for all the alginate solutions by addition of four divalent cations over sol‐gel transition process. The values of exponent b in the power‐law relation \documentclass{article}\pagestyle{empty}\begin{document}$ {\eta \propto \dot \gamma }$\end{document} were found in the range of −0.3 ∼ −0.6. It is suggested that a considerable portion of divalent cations remains in a cross‐linking state even under shear flow. The results obtained from thixotropy measurements indicate the existence of a major framework formed in the gel‐like and well‐gelled samples, which can be maintained until shear rate (or shear stress) reaches a threshold value. © 1994 John Wiley & Sons, Inc.
A quantum mechanical study of the intrinsic helix‐forming tendency of α‐aminoisobutyric acid and dehydroalanine residues
Authors: Alemán Carlos
Published: December 2004

A quantum mechanical study to compare the ability of α‐aminoisobutyric acid (Aib), de‐hydroalanine (ΔAla), and alanine (Ala) residues to stabilize helical conformations has been performed. To address the study, the oligopeptides Xn (X = Aib, ΔAla and Ala), where n varies from 1 to 6, were computed with the AM1 semiempirical method. The results show that the residues modified at the Cα carbon atom, Aib and ΔAla, are better helical formers than Ala. Thus, a cooperative energy effect was found for both residues, and especially for ΔAla. These terms permit the understanding the different conformational behaviors between Ala and its Cα‐modified residues Aib and ΔAla. This trend is important for de novo protein design, where Aib and ΔAla must be considered useful residues in the design of synthetic helical motifs. © 1994 John Wiley & Sons, Inc.
Conformational and binding properties of chicken liver basic fatty acid binding protein in solution
Authors: Schievano Elisabetta , Quarzago Daniela , Spadon Paola , Monaco Hugo Luis , Zanotti Giuseppe , Peggion Evaristo
Published: December 2004

The conformation of basic fatty acid binding protein from chicken liver and the binding properties of the apo protein toward 11‐dansylamino‐undecanoic acid were investigated by CD and fluorescence spectroscopy. In one set of experiments the binding process was followed by the appearance of induced optical activity in the absorption region of the dansyl chromophore. In a second set of experiments the binding process was followed by the large enhancement of emission fluorescence of the dansyl fluorophore. From the saturation curves, the stoichiometry of the complex and the binding constant of the fatty acid to the protein were precisely determined. The values of the dissociation constant determined with the two methods were in excellent agreement: we obtained KD = (1.0 ± 0.1) · 10−6M in a 0.9 : 1 stoichiometry. The native conformation of the protein is remarkably stable in a variety of solvent systems, including acetonitrile–water, ethylene glycol–water, and dicxane–water of various compositions. The CD results also showed that the binding of the fatty acid does not induce any appreciable change in the protein conformation. In a mixture of water and 2,2,2‐trifluoroethanol 1 : 9 (v/v), the native conformation collapses and a new ordered structure is formed, characterized by a high amount of α‐helix. © 1994 John Wiley & Sons, Inc.
PAPQMD/AM1 Parametrization of the bonded term of aromatic biomolecules
Authors: Alemán Carlos , Orozco Modesto
Published: December 2004

The suitability of the PAPQMD/AM1 (Program for Approximate Parametrization from Quantum Mechanical Data/based on AM1 calculations) strategy to provide force‐field parameters for large heteroaromatic compounds was studied. For this purpose, PAPQMD/AMI stretching and bending parameters for adenine, cytosine, thymine, guanine, and uracil were computed and compared with experimentally derived force‐field parameters. Furthermore, equilibrium geometries and vibrational spectra for the five nucleic acid bases obtained from molecular mechanical calculations using both PAPQMD/AM1 and AMBER (Assisted Model Building with Energy Refinement) All Atoms force fields were compared with the available experimental data. © 1994 John Wiley & Sons, Inc.
IR and Raman spectroscopic studies of the interaction of trehalose with hen egg white lysozyme
Authors: Belton P. S. , Gil A. M.
Published: December 2004

Infrared and Fourier transform Raman spectra are reported for dried mixtures of trehalose and lysozyme. The Raman spectra show effects on the protein amide I band and some sugar bands that are not present when the components are dried separately. Comparison of ir spectra with those published previously show significant differences. It is concluded that these arise because of differences in the extent of drying of the moisture, and that, contrary to some claims, vibrational spectroscopy does not so far show any clear evidence of specific trehalose/protein interactions and that results may be interpreted in terms of entrapment of water within the mixture. © 1994 John Wiley & Sons, Inc.
Design, synthesis, and conformation of a model peptide of endothelin with cystine‐stabilized α‐helix motif
Authors: Mihara Hisakazu , Tomizaki Kin‐Ya , Nishino Norikazu , Fujimoto Tsutomu , Tamaoki Haruhiko , Kobayashi Yuji
Published: December 2004

A model 16‐peptide of endothelin‐1 (MET‐1), which has the minimized sequence homology to the corresponding pan of endothelin‐1 (ET‐1), was designed to confirm the cystine‐stabilized α‐helix motif. The model structure consists of an extended structure, a β‐turn part, and an α‐helix structure that is stabilized by two disulfide bonds. The α‐helix segment was designed to emphasize the amphiphilic nature. In order to combine the extended structure and the α‐helix segment, a D‐Ala‐Pro sequence was selected to fix the β‐turn. The model endothelin 16‐peptide amide was synthesized by solid‐phase synthesis on a 4‐methylbenzhydrylamine resin. Its conformation was examined by CD and two‐dimensional (2D) 1H‐nmr measurements. MET‐1 showed similar CD patterns to ET‐1 in both buffer and 50% aqueous trifluoroethanol solution. The 2D nmr experiments in 50% aqueous ethylene glycol revealed that MET‐1 closely resembles the conformation of ET‐1 with an extended structure, an α‐helix, and a β‐turn unit in the same position of the sequence. Furthermore, model peptides without disulfide bond(s) could not assume a stable structure in aqueous solution, while they did have similar α‐helical content in 50% trifluoroethanol with MET‐1. When the two disulfide bridges were simultaneously formed, the peptide with the correct disulfide bonds (MET‐1) was obtained in threefold excess to the isomer (apamin type. MET‐2). These findings obtained by the modeling of ET‐1 showed an important role for the stabilization of peptide conformation with disulfide bonds. © 1994 John Wiley & Sons, Inc.
Conformation of CD4‐derived cyclic hexapeptides by nmr and molecular dynamics
Authors: Ma Sougen , McGregor Malcolm J. , Cohen Fred E. , Pallai Peter V.
Published: December 2004

Two cyclic hexapeptides, cyclo[Ala1‐D‐Ala2‐Ser3‐Phe4‐Gly5‐Ser6] and cyclo[Ala1‐Gly2‐Ser3‐Phe4‐Gly5‐Ser6], derived from the loop portion of the C′C″ ridge of CD4, were characterized by high‐resolution nmr spectroscopy and simulated annealing studies. In DMSO‐d6 both of these peptides display a single conformer on the nmr time scale with two intramolecular H‐bond (1 ← 4) stabilized β‐turns at positions 2–3 and 5–6. The nmr derived distance constraints were used in simulated annealing calculations to generate the solution structures. These structures adopt energetically comparable conformational substates that are not resolvable on the nmr time scale. In aqueous solution, the H‐bond stabilized β‐turn conformation for cyclo [Ala‐D‐Ala‐Ser‐Phe‐Gly‐Ser] is no longer the predominant structural form. Structures generated using molecular dynamics simulations with no experimental constraints were compared with those from nmr analysis. The correlation between these two sets of structures allows the use of molecular simulations as a predictive tool for the conformational analysis of small peptides. © 1994 John Wiley & Sons, Inc.
Crystal structure of cyclo(Pro‐Gly)3: Li complex: A model for ion transport by cyclo(Pro‐Gly)3
Authors: Thomas L. M. , Ramasubbu N. , Bhandary K. K.
Published: December 2004

The crystal structure of cyclo(Pro‐Gly)3 (PG3) complex with LiSCN (C22H30N7O6SLi) has been solved by x‐ray diffraction. The crystals belong to the space group R3 in the hexagonal setting with unit cell parameters of a = 12.581(1), c = 29.705(3) Å, V = 4072.0 Å3, Z = 6, Mr = 527.53, Dc = 1.23 g/cm3. The crystal structure was solved by direct methods using the program SHELXS‐86 and refined to an R value of 5.3% for 1645 reflections (I > 2σI). There are two conformers in the crystal structure. One conformer has three carbonyls on one side and three on the other side of the peptide plane. The other conformer has all six of the carbonyls on the same side of the peptide plane. Both of these conformers bind independently to a Li ion. Based on the conformers of the Li complex and other reported ion complexes formed by PG3, we propose a model for the transport of ions across the lipid membrane. The features of the model are as follows: (1) PG3 forms a hexameric stack in a lipid bilayer when complexing and transporting metal ions. (2) It undergoes a conformational flipping in order pass the ion along the channel. The energy required for the conformational change involved in the flipping of the PG3 molecule may be provided by the applied potential during ion transport. © 1994 John Wiley & Sons, Inc.
Molecular dynamics simulation of a leucine zipper motif predicted for the integrase of human immunodeficiency virus type I
Authors: Wang C. Y. , Yang C. F. , Lai M. C. , Lee Y. H. , Lee T. L. , Lin T. H.
Published: December 2004

We have used the molecular dynamics (MD) simulation package AMBER4 to search the conformation of a peptide predicted as a leucine zipper motif for the human immunodeficiency virus type I integrase protein (HIV IN‐LZM). The peptide is composed of 22 amino acid residues and its location is from Val 151 to Leu 172. The searching procedure also includes two known α‐helices that served as positive controls—namely, a 22‐residue GCN4‐p1 (LZM) and a 20‐residue poly(L‐alanine) (PLA). A 21‐residue peptide extracted from a cytochrome C crystal (CCC‐t) with determined conformation as a β‐turn is also included as a negative control. At the beginning of the search, two starting conformations—namely, the standard right‐handed α‐helix and the fully stretched conformations—are generated for each peptide. Structures generated as standard α‐helix are equilibrated at room temperature for 90 ps while structures generated as a fully stretched one are equilibrated at 600 K for 120 ps. The CCC‐t and PLA helices are nearly destroyed from the beginning of equilibration. However, for both the HIV IN‐LZM and the GCN4‐p1 LZM structures, there is substantial helicity being retained throughout the entire course of equilibration. Although helix propagation profiles calculated indicate that both peptides possess about the same propensity to form an α‐helix, the HIV IN‐LZM helix appears to be more stable than the GCN4‐p1 one as judged by a variety of analyses on both structures generated during the equilibration course. The fact that predicted HIV IN‐LZM can exist as an α‐helix is also supported by the results of high temperature equilibration run on the fully stretched structures generated. In this run, the RMS deviations between the backbone atoms of the structures with the lowest potential energy (PE) identified within every 2 ps and the structure with the lowest PE searched in the same course of simulation are calculated. For both the HIV IN‐LZM and the GCN4‐p1 LZM, these rms values decrease with the decrease of PE, which indicates that both structures are closer in conformations as their PEs are moved deeper into the PE well. © 1994 John Wiley & Sons, Inc.
Comparative interactions of magnesium and calcium counterions with polygalacturonic acid
Authors: Malovíková Anna , Rinaudo Marguerite , Milas Michel
Published: December 2004

The comparative interaction of Mg2+ and Ca2+ counterions on carboxyl groups of polygalacturonic acid is developed. Ultracentrifugation, conductimetry, potentiometry, and CD were used in this work. Evidence is provided for a simple electrostatic interaction of Mg2+ counterions; on the opposite side, cooperative interaction of Ca2+ counterions is again demonstrated, causing chain–chain association. © 1994 John Wiley & Sons, Inc.
Physical and chemical microstructure of spider dragline: A study by analytical transmission electron microscopy
Authors: Thiel Brad L. , Kunkel Dennis D. , Viney Christopher
Published: December 2004

We report the first direct observations of the physical and chemical microstructure of spider dragline, revealed by analytical transmission electron microscopy. Individual crystallites were imaged within the amorphous matrix. They are irregularly shaped, approximately 70–100 nm in diameter, and uniformly distributed throughout the matrix. Electron diffraction determined their space group to be P21. The corresponding orthogonal cell has lattice parameters of a = 13.31 Å (β‐sheet repeat), b = 9.44 Å (interchain repeat within β‐sheets), and c = 20.88 Å (repeat along polypeptide chain). Electron energy loss spectroscopy indicated compositional variations within the matrix, and between the crystallites and matrix. Most notably, calcium was found exclusively in the crystallites. Attempts to produce synthetic analogues of dragline, which exhibits an unparalleled combination of strength, stiffness, and toughness, cannot depend solely on duplicating the constituent proteins. The complex hierarchical microstructure of the natural material must be taken into account. © 1994 John Wiley & Sons, Inc.
Fractal‐like patterns in DNA films, B form at 0% relative humidity, and antiheteronomous DNA: An ir study
Authors: Sclavi B. , Peticolas W. L. , Powell J. W.
Published: December 2004

This report details the observation of (a) the intact double helix of DNA at 0% relative humidity in poly(dA) · poly(dT) and poly (dA‐dT) · poly (dA‐dT) films, (b) the fractal‐like growth of DNA crystals in films of poly (dA) · poly(dT), and (c) poly(dA) · poly(dT) with adenines in the B form and thymines in the A form. Observation (a) is based on the behavior of the middle ir signature of double‐helical base stacking, the 1714 cm−1 peak, at low water activity. This observation is modeled as a trapping of water in the polycrystalline part of these films. We interpret the glycosidic region of the middle ir spectra of the polycrystalline films of poly (dA) · poly (dT) at 0% relative humidity to indicate that at least part of the adenine strand in is the B conformation and the thymine strand is in the A form, whereas previous assignments of poly (dA) · poly (dT) films at 75% relative humidity indicated the opposite strand conformation assignment [E. Taillandier et al. (1987) Biochemistry, Vol. 26 p. 3361]. © 1994 John Wiley & Sons, Inc.
Thrombin‐bound conformation of a cyclic anticoagulant peptide using transferred nuclear Overhauser effect (NOE), distance geometry, and NOE simulations
Authors: Ning Q. , Ripoll D. R. , Szewczuk Z. , Konishi Y. , Ni F.
Published: December 2004

A cyclic hirudin C‐terminal fragment, even truncated to eight residues, retains higher activity in binding to thrombin compared with its linear analogue of the same peptide length. In this paper, we report the results of a conformational study of a cyclic hirudin peptide 55–62 bound to the exosite of thrombin. Based on transferred NOE data and molecular modeling, conformation of the 18‐membered ring was well defined with little mobility in the loop region. The backbone conformations of residues Glu (58) to Lys (61) are very similar to those in a native 11‐residue linear peptide in the thrombin‐bound state [Ni et al. (1990) Biochemistry, vol. 29, pp. 4479–4489; Skrzypczak‐Jankun et al. (1991) Journal of Molecular Biology, vol. 221, pp. 1379–1393]. The side chain of Ile (59), the most critical residue, assumes a gauche− conformation, as observed in linear hirudin peptides. The bound conformations of residues Phe (56) and Glu (57) are defined by an iterative procedure involving the matching of computed and experimental transferred NOE intensities. The exosite of thrombin appears to be very specific to both the backbone and the side‐chain conformations of the hirudin C‐terminal peptides, especially those of residues Phe (56) and Ile (59). © 1994 John Wiley & Sons, Inc.
Observation of a sterically unfavorable side‐chain conformation in a leucyl residue: Crystal and molecular structure of L‐leucyl–L‐leucine · DMSO solvate
Authors: Mitra Shome Nath , Subramanian E.
Published: December 2004

The crystal structure of a dipeptide L‐leucyl–L‐leucine (C12H24N2O3) has been determined. The crystals are monoclinic, space group P21, with a = 5.434(4) Å, b = 15.712(7) Å, c = 11.275(2) Å, β = 100.41(1)°, and Z = 2. The crystals contain one molecule of dimethyl sulfoxide (DMSO) as solvent of crystallization for each dipeptide molecule. The structure has been solved by direct methods and refined to a final R index of 0.059 for 920 reflections (sinθ/λ ⩽ 0.60 Å−1) with I ⩾ 2σ (I). The trans peptide unit shows substantial degree of non‐planarity (Δω = 14°). The peptide backbone adopts an extended conformation with torsion angles of ψ1 = 138(1)°, ω1 = 166(1)°, ϕ2 = − 149.3(7)°, ψ21 = 164.2(7)°, and ψ22 = − 15(1)°. For the first leucyl residue, the side‐chain conformation is specified by the torsion angles 1χ1 = 176.7(7)°, 1χ21 = 62(1)°, 1χ22 = − 177.4(8)°; the second leucyl residue adopts a Sterically unfavorable conformation with 2χ1 = 61(1)°, 2χ21 = 97(1)°, and 2χ22 = −151(1)°. The packing involves head‐to‐tail interaction of peptide molecules and segregation of polar and nonpolar regions. The DMSO molecule is strongly hydrogen bonded to the terminal NH group. © 1994 John Wiley & Sons, Inc.
Solution structure and dynamics of a glycoinositol phospholipid (GIPL‐6) from Leishmania major
Authors: Weller C. T. , McConville M. , Homans S. W.
Published: December 2004

By use of a combination of 1H nuclear Overhauser effect measurements, restrained molecular dynamics simulations, and 13C spin–lattice relaxation time measurements, the solution behavior of the glycan moiety of a complex glycoinositol phospholipid termed G1PL‐6, from the protozoan parasite Leishmania major has been determined. The glycan moiety of GIPL‐6 has the following structure, which is characterized by the presence of an internal β‐galactofuranose residue:
magnified image
The glycan does not adopt a single conformation in solution, due to significant torsional variations about the two phosphodiester linkages and certain glycosidic linking in the molecule. The present of the internal galactofuranose residue results in an average solution conformation of the oligosaccharide, which resembles a “hairpin,” with the galactofuranose residue at the apex. © 1994 John Wiley & Sons, Inc.
Conformational differences between cis and trans proline isomers of a peptide antigen representing the receptor binding domain of Pseudomonas aeruginosa as studied by 1H‐nmr
Authors: Mcinnes Campbell , Kay Cyril M. , Hodges Robert S. , Sykes Brian D.
Published: December 2004

A 17‐residue disulfide‐bridged peptide (PAK 128–144) corresponding to the C‐terminus of Pseudomonas aeruginosa pilin strain K has been studied by one‐ and two‐dimensional nmr techniques. This synthetic immunogen has been found to exist as two distinct conformations in solution, which have been demonstrated to arise as a result of the isomerization of the I138‐P139 amide bond. The two isomers occur in the ratio of 3 : 1 trans to cis at 5°C. Sequential assignments for both forms have been accomplished through the use of nuclear Overhauser enhancement spectroscopy (NOESY) spectra and most side‐chain resonances have been assigned using a combination of correlated spectroscopy, total correlated spectroscopy, and NOESY spectra. The presence of the cis isomer, which is considerably more predominant in the oxidized peptide, was confirmed by the observation of the characteristic NOEs between P139 and the preceding residue. Further corroboration was given by the disappearance of the cis resonances in the spectrum of the P139A analogue of PAK 128–144. From observation of the differences in the chemical shifts and amide proton temperature coefficients of the two isomers, it is apparent that the two forms differ markedly in their solution conformation. The biological implications of the isomerization are discussed. © 1994 John Wiley & Sons, Inc.
Prediction of the conformational requirements for binding to the κ‐opioid receptor and its subtypes. I. Novel α‐helical cyclic peptides and their role in receptor selectivity
Authors: Collins Nathan , Hruby Victor J.
Published: December 2004

A conformational search of two similar κ‐selective cyclic Dynorphin A (Dyn A) analogues is presented. Dyn A1–11‐NH2(1) and Dyn A1–11‐NH2 (2) are not only highly potent κ‐selective peptides but they also exhibit exceptional selectivity for κ receptors in the central (brain) vs. the peripheral (ileum) systems. Molecular mechanics systematic searching of the conformational preferences of the cyclic moieties of 1 and 2 produced 741 and 1003 starting ring structures, which were minimized at two dielectric constants of 2.0 and 80.0 in the AMBER force field. By rms superimposition, these low energy structures were grouped into conformational families for each ring system minimized at each dielectric. Comparison of the lowest energy structure of each of these families demonstrated that two (labeled A and B) were found as low energy ring systems for both 1 and 2 after minimization at either dielectric constant. These two structures are thus predicted to be the putative binding conformations for Dynorphin A at receptors in the brain. Interestingly, one of these putative binding structures exhibited an α‐helical conformation in the disulfide bridged ring that has not been observed for small cyclic peptides of this nature before. Molecular dynamics simulation of the helical binding structures indicated that the helical configuration in 2 is lower in energy and is more confor‐mationally stable than that of 1. We correlate this with the increased selectivity and potency of 2 for κ receptors in the brain compared to the periphery, implying that this may be due to an α‐helical conformation in the cyclized address or helical induction in the message sequence. © 1994 John Wiley & Sons, Inc.
Effect of succinylation on the membrane activity and conformation of a short cecropin A‐melittin hybrid peptide
Authors: Fernández Imma , Ubach Josep , Reig Francesca , Andreu David , Pons Miquel
Published: December 2004

A 15‐residue hybrid peptide (KWKLFKKIGAVLKVL‐amide) incorporating partial sequences of cecropin A and melittin causes the release of carboxyfluoresceine encapsulated in phosphatidylcholine liposomes. Succinylation of the amino groups in the N‐terminus and lysine side chains inhibits the effect of this peptide on liposome permeability. Conformational analysis of the parent peptide and its succinyl derivative by CD and nmr indicates that both peptides form amphipathic α‐helices in the presence of hexafluoro‐2‐propanol, but only the unmodified peptide acquires a relevant level of α‐helical conformation in the presence of liposomes. © 1994 John Wiley & Sons, Inc.