bluuebunny/crossref_metadata_2025 huggingface dataset:
The use of UV‐visible spectroscopy for the determination of hydrophobic interactions between neuropeptides and membrane model systems
Authors: Young John K. , Graham William H. , Beard Debbie J. , Hicks Rickey P.
Published: December 2004

Ultraviolet‐visible spectroscopy has been used as a rapid method to evaluate the hydrophobia interactions between a series of cationic and zwitterionic neuropeptides and dipeptides with the hydrophobia core of two membrane model systems; sodium dodecyl sulfate and lysophosphatidylcholine micelles. If a hydrophobia interaction occurs, a 1−nm bathochromic shift is observed in the uv‐visible spectrum of the aromatic side chains when going from aqueous solution to a micellar solution. The aromatic residues of substance P, bradykinin, and Des‐Arg9 bradykinin all exhibited the 1−nm bathochromic shift in the presence of sodium dodecyl sulfate while those of Met‐enkephalin did not. The opposite effects were observed in the presence of lysophosphatidylcholine micelles. © 1992 John Wiley & Sons, Inc.
Hydrophobicity of amino acid residues: Differential scanning calorimetry and synthesis of the aromatic analogues of the polypentapeptide of elastin
Authors: Luan Chi‐Hao , Parker Timothy M. , Gowda D. Channe , Urry Dan W.
Published: December 2004

Relative hydrophobicities of aromatic amino acid residues are investigated by using differential scanning calorimetry (DSC) on 10 synthetic copolypentapeptides of poly(VPGVG) of elastin. Utilizing the hydrophobic‐driven process of the inverse temperature transition exhibited by these polypentapeptides in aqueous solution, the relative hydrophobicities of Phe, Trp, and Tyr residues are determined by the critical temperature and heat of the transition. The DSC data for the aromatic residue containing copolypentapeptide aqueous solution indicate that tryptophan is the most hydrophobic amino acid residue, phenylalanine the third most hydrophobic on basis of transition temperature and the second on basis of transition heat. For tyrosine, significant differences are observed between the phenolic and the phenoxide anionic states. At pH 7, where tyrosine is protonated, it is found to be the second most hydrophobic amino acid residue on the basis of the transition temperature, whereas on the basis of the heat of transition, it is loss hydrophobic than both tryptophan and phenylalanine. Changing the pH from pH 7 to pH 12, for example, for poly[0.8(VPGVG), 0.2(VPGYG)] in aqueous solution shifts the transition temperature from 7 to 49°C with a dramatically reduced heat. On the basis of both the transition temperature scale and the heat of transition, the hydroxylated tyrosine appears less hydrophobic than glycine. © 1992 John Wiley & Sons, Inc.
Structural investigation of helices II, III, and IV of B. megaterium 5S ribosomal RNA by molecular dynamics calculations
Authors: Kim Jong Hwa , Marshall Alan G.
Published: December 2004

The structures of the helices II‐III region and the helix IV region of B. megaterium 5S rRNA have been examined by means of energy minimization and molecular dynamics calculations. Calculated distances between neighboring hydrogen‐bonded imino protons in helices II, III, and IV were between 3.5 and 4.5 Å. The overall axis for the helices II‐III region is warped rather than straight. Formation of additional Watson‐Crick base pairs in loop B and loop C was not evident from the atomic positions calculated by molecular dynamics. Bases in loop C are well stacked, showing no significant change during dynamics. Bulge migration in helix III does not seem to be possible; the helices II‐III region prefers one conformation. Helix II is more stable than helix III. Five base pairs in helix IV were sufficiently stable to establish that helix IV is terminated by a hairpin loop of three nucleotides. U87 protrudes from loop D. Structures of the helices II‐III segment and the helix IV segment of B. megaterium 5S rRNA obtained by molecular dynamics were generally consistent with the solution structure inferred from high‐field proton nmr spectroscopy. © 1992 John Wiley & Sons, Inc.
A thermodynamic analysis of calcium–alginate gel formation in the presence of inert electrolyte
Authors: Nilsson Svante
Published: December 2004

The effect of mixed salt (1:1 and 2:1 electrolyte) on alginate (a charged polysaccharide) gel formation is analyzed within the Poisson‐Boltzmann cell model utilizing experimental data from the literature. The concentration of calcium ions needed to induce gelation of alginate goes through a minimum as 1 : 1 electrolyte is added. The theoretical model can account for this in a qualitative manner. According to the theoretical model, however, it is only in terms of concentrations that the minimum exists. In terms of chemical potentials for the ions (or salt) the curve is monotonic. The effect is due to the highly nonideal interactions in polyelectrolyte solutions when the total salt content is low. © 1992 John Wiley & Sons, Inc.
Stacking interactions of ApA analogues with modified backbones
Authors: Kang Hunseung , Chou Ping‐Jung , Johnson W. Curtis , Weller Dwight , Huang Sung‐Ben , Summerton James E.
Published: December 2004

CD spectra have been measured as a function of temperature for a number of ApA analogues with modified backbones. Oligonucleotides with these modified backbones are being used as antisense agents having potential as viral therapeutics. Results of these studies show that when a carbonyl is substituted for the phosphate to produce an uncharged backbone, the analogues that have either sugar or morpholino substitution do not stack. In contrast, when a morpholino group is substituted for the sugar and the phosphate is modified so as to be uncharged, there is strong base stacking. Stacking interactions in the phosphorus‐linked morpholino analogues are at least as strong as those found in d (ApA). The stacking interactions in ApA are weak by comparison. Singular value decomposition demonstrates that the stacking is two state, and Taylor series decomposition yields a coefficient that measures base stacking interactions. The van't Hoff equation is applied to the base stacking coefficient from the Taylor series fitting to give thermodynamic parameters. © 1992 John Wiley & Sons, Inc.
A synthetic analogue for the active site of plant‐type ferredoxin: Two different coordination isomers by a four‐Cys‐containing [20]‐peptide
Authors: Ueyama Norikazu , Ueno Satoru , Nakamura Akira , Wada Keishiro , Matsubara Hiroshi , Kumagai Shin‐Ichiro , Sakakibara Shumpei , Tsukihara Tomitake
Published: December 2004

The (Fe2S2)2+ complex of an artificial 20‐peptide ligand, Ac‐Pro‐Tyr‐Ser‐Cys‐Arg‐Ala‐Gly‐Ala‐Cys‐Ser‐Thr‐Cys‐Ala‐Gly‐Pro‐Leu‐Leu‐Thr‐Cys‐Val‐NH2, containing an invariant Cys‐A‐B‐C‐D‐Cys‐X‐Y‐Cys (A, B, C, D, X, Y = amino acid residues) fragment of plant‐type ferredoxins was synthesized by a ligand exchange method with [Fe2S2(S‐t‐Bu)4]2−. 1H‐nmr spectroscopic and electrochemical data of the complex indicate the presence of two coordination isomers. One of them having a Cys‐X‐Y‐Cys bridging coordination to the two Fe(III) ions, has the (Fe2S2)2+ core environment similar to those of the denatured plant‐type ferredoxins and exhibits a positive shifted redox potential at −0.64 V vs saturated colonel electrode (SCE) in N,N‐dimethylformamide (DMF). Another isomer with the Cys‐A‐B‐C‐D‐Cys bridging coordination shows a negative redox potential at −0.96 V vs SCE in DMF. © 1992 John Wiley & Sons, Inc.
Peptide hormone–membrane interactions: The aggregational and conformational state of lipo‐gastrin derivatives and their receptor binding affinity
Authors: Romano R. , Musiol H.‐J. , Weyher E. , Dufresne M. , Moroder L.
Published: December 2004

The (2RS) −1,2‐dipalmitoyl−3‐mercaptoglycerol/‐, (2RS) −1,2‐dimyristoy1–3‐mercaptogly‐cerol/−, and (2RS)‐1‐myristoy1–2‐palmitoy1–3‐mercaptoglycerol/maleoyl‐β‐alanyl‐[Nle15]‐human‐gastrin‐(2–17) adducts were prepared as lipo‐gastrin derivatives of explicitly primary amphiphilic properties. As representative of this class of lipo‐gastrins, the dimyristoyl derivative has been thoroughly characterized in its aggregational state since, among the three compounds, theoretically it should exhibit the lowest degree of lipid character. It aggregates in aqueous solution to form monodispersed unilamellar spherical vesicles with dislocation of the peptide moiety at the bilayer surface in predominantly unordered structure. The liposomes are remarkably stable toward solubilization with trifluoroethanol and toward vesicle to micelle transition with neutral and negatively charged surfactants even above their critical micellar concentrations. Asymmetric fusion with the detergent micelles induces pplydispersion of the liposomes in terms of shape and size without affecting in significant manner the mode of display of the gastrin portions at the bilayer surface. Only the positively charged hexadecyltrimethylammonium hydroxide provokes the collapse of the vesicles into mixed micelles with concomitant altered dislocation of the gastrin‐peptide in the new aggregational state. Despite the lipid properties of the gastrin derivatives, i.e., formation of lipocomes, they retain remarkable receptor affinities (IC50 = 1.5· 10−9M for myristoyl‐palmitoyl‐gastrin, IC50 = 2.0 · 10−9M for dimyristoyl‐gastrin and IC50 = 3.1 · 10−9 M for dipalmitoylgastrin vs IC50 = 2.8− 10−10M for Nle15‐gastrin). Since the displacement of radiolabeled Nle15‐gastrin from rat pancreatic acinar cell line membrane preparations by both the parent gastrin hormone and the three lipogastrins occurs in parallel manner, the data support a mechanism of receptor occupancy via accumulation of the gastrins at the membrane surface and their two‐dimensional diffusion to the target receptor. Thereby the differentiated decrease of affinity in function of fatty acid chain length has to be attributed to the energetically more or less favored transfer of the monomers from the donor vesicles to the acceptor membranes. Moreover, according to this model migration of the lipogastrins with their interdigitating difattyacyl moieties should be delayed, again in lipid structure‐dependent manner, in comparison to the parent gastrin molecule, which is free to float in the membrane interfacial phase. © 1992 John Wiley & Sons, Inc.
Combined use of molecular dynamics simulations and NMR to explore peptide bond isomerization and multiple intramolecular hydrogen‐bonding possibilities in a cyclic pentapeptide, cyclo (Gly‐Pro‐D‐Phe‐Gly‐Val)
Authors: Liu Zhi‐Ping , Gierasch Lila M.
Published: December 2004

The conformational behavior of a model cyclic pentapeptide—cyclo(Gly‐L‐Pro‐D‐Phe‐Gly‐L‐Val)—has been explored through the combined use of in vacuo molecular dynamics simulations and a range of nmr experiments (preceding paper). The molecular dynamics analysis suggests that, despite the conformational constraints imposed by formation of the pentapeptide cycle, this pentapeptide undergoes conformational transitions between various hydrogen‐bonded conformations, characterized by low energy barriers. An inverse γ turn with Pro in position i+1 and a γ turn with D‐Phe in position i+1 are two alternatives occurring frequently. Like other DLDDL cyclic pentapeptides, cyclo (Gly‐Pro‐D‐Phe‐Gly‐Val) is also stabilized by an inverse γ‐turn structure with the β‐branched Val residue in position i + 1, and this hydrogen bond is retained in the different conformational families. The γ‐turn around D‐Phe3 and the inverse γ turn around Val5 are consistent with the nmr observations. 3JNH—CHα coupling constants of the all‐trans forms were calculated from one of the molecular dynamics trajectories and are comparable to nmr experimental data, suggesting that the conformational states visited during the simulation are representative of the conformational distribution in solution. In addition to the equilibrium among various hydrogen‐bonded all‐trans conformers, the observation in nmr spectra of two sets of resonances for all peptide protons indicated a slow conformational interconversion of the Gly‐Pro peptide bond between trans and cis isomers. The activation energy between these two conformers was determined experimentally by magnetization transfer and was calculated by high temperature constrained molecular dynamics simulation. Both methods yield a free energy of activation of ca. 20 kcal/mol. Furthermore, the free energy of activation is dependent on the direction of rotation of the Gly‐Pro peptide bond. © 1992 John Wiley & Sons, Inc.
Impact of a micellar environment on the conformations of two cyclic pentapeptides
Authors: Bruch Martha D. , Rizo Josep , Gierasch Lila M.
Published: December 2004

In an effort to explore the influence of interfacial environments on reverse turns, we have performed a detailed analysis by nmr of the solution conformations of two cyclic pentapeptides in sodium dodecyl sulfate (SDS) micelles. The first peptide, cyclo (D‐Phe1‐Pro2‐Gly3‐D‐Ala4‐Pro5), adopts a single rigid conformation in solution (either chloroform or dimethylsulfoxide) and in crystals, whereas the second, cyclo (Gly1‐Pro2‐D‐Phe3‐Gly4‐Val5), is much more flexible and adopts different conformations in the crystal and in solution. Both of these peptides are solubilized by SDS micelles, and nmr relaxation rates indicate that they are both partially immobilized by interaction with the micelles. Furthermore, some amide protons in both peptides participate in hydrogen bonds with water. In the presence of micelles, the former peptide retains a conformation essentially the same as that found in crystals and in solution, which consists of a β turn and an inverse γ turn. However, the micellar environment has a significant effect on the latter peptide. In particular, the population of a conformer containing a cis Gly‐Pro peptide bond is increased significantly. The most likely conformation of the cis isomer, determined by a combination of nmr and restrained molecular dynamics, contains a Gly1‐Pro2 δ turn and a γ turn about D‐Phe3. The nmr data on the trans isomer indicate that this isomer is averaging between two conformations that differ mainly in the orientation of the D‐Phe3‐Gly4 peptide bond. © 1992 John Wiley & Sons, Inc.
Conformational analysis of met‐enkephalin in both aqueous solution and in the presence of sodium dodecyl sulfate micelles using multidimensional NMR and molecular modeling
Authors: Graham William H. , Carter Eugene S. , Hicks Rickey P.
Published: December 2004

Proton and 13C chemical shift assignments are reported for the neuropeptide Met‐enkephalin (ME) in both aqueous solution and in the presence of 50 mM sodium dodecyl sulfate (SDS). Rotating frame nuclear Overhauser enhancement spectroscopy was used to qualitatively describe interproton distances. These distances were then used as restraints in the distance geometry based molecular modeling program Dspace, developed by Hare Research to generate sets of conformations of ME. The resulting aqueous solution conformations of ME were determined to exhibit characteristic of an extended random‐coil polypeptide with no distinguishable secondary structure. The resulting set of solution conformations of ME in the presence of 50 m M SDS exhibited characteristics of an amphiphilic type IV β turn that are stabilized by hydrophobic aromatic‐aromatic interactions between the side chains of Tyr1 and Phe4. © 1992 John Wiley & Sons, Inc.
Crystal structure, conformational analysis, and molecular dynamics of tetra‐O‐methyl‐(+) ‐catechin
Authors: Fronczek Frank R. , Hemingway Richard W. , Mcgraw G. Wayne , Steynberg Jan P. , Helfer Carin A. , Mattice Wayne L.
Published: December 2004

The structure of tetra‐O‐methyl‐ (+) ‐catechin has been determined in the crystalline state. Two independent molecules, denoted structure A and structure B, exist in the unit cell. Crystals are triclinic, space group P1, a = 4.8125(2) Å, b = 12.9148(8) Å, c = 13.8862(11) Å, α = 86.962(6) °, β = 89.120(5)°, γ = 88.044(5)°, Z = 2, Dc = 1.336 g cm−3, R = 0.033 for 6830 observations. The heterocyclic rings of the crystal structures are compared to previous results for 8‐bromotetra‐O‐methyl‐(+)‐catechin, penta‐O‐acetyl‐(+)‐catechin, and (−) ‐epicatechin. One of the two molecules has a heterocyclic ring conformation similar to that observed previously for (−)‐epicatechin, and the other has a heterocyclic ring conformation similar to one predicted earlier in a theoretical analysis of dimers of (+)‐catechin and (−) ‐epicatechin. Both structure A and structure B in the crystal have heterocyclic ring conformations that place the dimethoxyphenyl substituent at C(2) in the equatorial position. However, this heterocyclic ring conformation does not explain the proton nmr coupling constant measured in solution. Molecular dynamics simulations show an equatorial ⇌ axial interconversion of the heterocyclic ring, which can explain the nmr results. © 1993 John Wiley & Sons, Inc.
Vibrational CD study of the thermal denaturation of poly(rA) · poly(rU)
Authors: Yang Ligang , Keiderling Timothy A.
Published: December 2004

The vibrational cd (VCD) of a double‐stranded RNA, poly(rA) ‐ poly(rU), at pH 7 and moderate added salt concentration (0.1M) has been measured in both the base‐stretching and phosphate‐stretching regions of the ir as a function of temperature. The data in both cases show two distinct phase transitions. The first is from double‐ to a triple‐stranded form, and the second is from triple‐ to single‐stranded forms, which still retain substantial local order even up to 80°C. The nature of these transitions has been identified by comparison of the VCD and ir absorption spectra of the initially double‐stranded samples with those of single‐stranded poly(rA) and poly(rU) and with triple‐stranded poly‐(rA) ‐poly‐(rU) poly (rU). The large differences in the VCD band shapes allows positive identification of the intermediate and final states. Thus under VCD‐concentration conditions, a simple helix‐to‐coil transition can be eliminated for poly (rA ) ‐ poly (rU) while such a two‐step transition can be seen at low salt conditions. All of these observations are consistent with previous studies of the phase transitions of poly (rA) ‐ poly (rU) under various salt conditions. Additionally, the VCD is indicative of premelting for all the triple‐, double‐, and single‐strand complexes studied. The triple‐strand complex did not show disproportionation to double strand on heating under these added salt conditions. The unusual VCD pattern for low temperature poly (rA) ‐ poly (rU), as compared to high GC content RNAs and DNAs, is qualitatively, but not quantitatively, explained using exciton coupling of localized dipolar transitions in each type of base within the strand. © 1993 John Wiley & Sons, Inc.
Exhaustive conformational search and simulated annealing for models of lattice peptides
Authors: Brower R. C. , Vasmatzis George , Silverman Michael , Delisi Charles
Published: December 2004

We consider simple lattice models for short peptide chains whose states can be exhaustively enumerated to find the lowest energy conformation. Using these exact results and numerical simulations, we compute the distributions for the mean time tN, required to find the global minimum energy state by simulated annealing (SA), as a function of N, the number of units in the chain. On the basis of scaling arguments, the time tN, to find the global minimum energy of longer chains, beyond the range covered by exhaustive enumeration, can be estimated. On the basis of the observed exponential increase in folding time of the standard SA algorithms, it is imperative that better algorithms be found for minimizing longer chains. © 1993 John Wiley & Sons, Inc.
A cooperative self‐consistent microscopic theory of thermally induced melting of a repeat sequence DNA polymer
Authors: Chen Y. Z. , Prohofsky E. W.
Published: December 2004

We attempt to extend the modified self‐consistent phonon theory to describe thermal fluctuational base‐pair opening of repeat sequence DNA polymers in the helix–coil transition region as well as in the premelting region. A microscopic base‐pair open state is introduced and the effect of this open state is taken into account self‐consistently in a mean field system that models the DNA polymer. Our analysis indicates the structure of this open state changes with temperature in such a manner that on average a base pair opens and unstacks with its neighbors more completely as temperature increases. We apply this theory to a homopolymer—poly(dG) · poly(dC) to evaluate the base‐pair opening probability in a temperature range from 273 to 366.5 K. At 366.5 K the system undergoes cooperative melting. Our calculated base‐pair opening probabilities are in general agreement with several experimental estimates at room temperature. The calculated probabilities show typical melting curve behavior at temperatures close to the observed melting temperature. The cooperative modified self‐consistent phonon approximation approach becomes a viable microscopic theory of melting. © 1993 John Wiley & Sons, Inc.
The influence of hydration on the conformation of lysozyme studied by solid‐state 13C‐nmr spectroscopy
Authors: Gregory Roger B. , Gangoda Mahinda , Gilpin R. K. , Su Wen
Published: December 2004

13C proton decoupled cross‐polarization magic‐angle spinning nmr spectra of lysozyme are reported as a function of hydration. Increases in hydration level enhance the resolution of the spectra, particularly in the aliphatic region, but has no significant effect on either the rotating frame proton spin–lattice relaxation time or the cross‐relaxation time. The enhancement in spectral resolution with hydration is attributed to a decrease in the distribution of isotropic chemical shifts, which reflects a decrease in the distribution of conformational states sampled by the protein. Changes in the distribution of isotropic chemical shifts occur after the addition of water to the charged groups as coverage of the polar side chains and peptide groups takes place. The onset of this behavior occurs at a hydration level of about, 0.1–0.2 g water/g protein and is largely complete at about 0.3 g water/g protein, the same hydration range where changes in the heat capacity are observed. That hydrogen exchange of buried protons can occur at hydration levels significantly lower than those at which changes in the distribution of conformational states are first observed suggests that some motions that mediate exchange are already present in the dry protein. The preservation of efficient dipolar coupling indicates that the conformational rearrangements that do‐occur on hydration are small and do not involve any significant overall expansion of free volume or weakening of interactions that would increase the reorientational freedom of protein groups. © 1993 John Wiley & Sons, Inc.
Reversible effects of medium dielectric constant on structural transformation of β‐lactoglobulin and its retinol binding
Authors: Dufour Eric , Bertrand‐Harb Catherine , Haertlé Tomasz
Published: December 2004

The secondary structure transformation of β‐lactoglobulin from a predominantly β‐structure into a predominantly α‐helical one, under the influence of solvent polarity changes is reversible. Independent of the alcohol used — methanol, ethanol, or 2‐propanol — the midpoints of the observed structural transformation occur around dielectric constant ε ≈ 60. The structural change destroying the hydrophobic core formed by the β‐barrel structure leads, at room temperature, to the dissociation of the retinol/β‐lactoglobulin complex in the neighborhood of dielectric constant ε ≈ 50. However, when the dielectric constant of the medium is raised back to ε ≈ 70 by the decrease of the temperature, both the refolding of BLG into a β‐structure and the reassociation of the retinol/β‐lactoglobulin complex are observed. The esterification of β‐lactoglobulin carboxyl groups has two effects: on the one hand it accelerates the β‐strand → α‐helix transition induced by alcohols. On the other hand, the esterification of β‐lactoglobulin strengthens its interaction with retinol as it may be deduced from the smaller apparent dissociation constant of retinol/methylated β‐lactoglobulin complex. The binding of retinol to modified or unmodified β‐lactoglobulin has no influence (stabilizing or destabilizing) on the folding changes induced by alcohol. © 1993 John Wiley & Sons, Inc.
The effect of intrinsic curvature on supercoiling: Predictions of elasticity theory
Authors: Tobias Irwin , Olson Wilma K.
Published: December 2004

Elasticity theory of naturally curved rods is employed to study the effects of intrinsic curvature on the properties of the equilibrium conformations of supercoiled DNA. The results stand in sharp contrast to those obtained when the molecule is viewed as being straight in its relaxed form. Starting from very fundamental principles of the theory, we show that the torsion of an open segment with a curved duplex axis can vary when the temperature, and along with it, the intrinsic twist is changed. Conversely, an imposed helicity, such as might be associated with binding to a histone, can change the intrinsic twist. It is also shown that another consequence of the presence of naturally curved sequences is that the twist density will, in general, vary with position along the chain in all equilibrium states. Then portions of the molecule will be more or less susceptible to interaction with other agents sensitive to such a variation. Finally, some closed equilibrium global structures uniquely associated with intrinsic curvature are discussed. © 1993 John Wiley & Sons, Inc.
Synthesis and conformational analysis of N‐glycopeptides. II. CD, molecular dynamics, and nmr spectroscopic studies on linear N‐glycopeptides
Authors: Perczel András , Kollát Emma , Hollósi Miklós , Fasman Gerald D.
Published: December 2004

The comprehensive structural analysis reported herein of eight N‐glycopeptides, in three different solvents, is based on quantitative CD experiments, homonuclear nuclear Overhauser effect measurements, and molecular dynamics (MD) calculations. Although several orientations of the two amide planes attached to the carbohydrate pyranose ring are possible, according to NOE, CD data, and MD simulations, of all of the glycopeptide models, regardless of the type of the carrier peptide, only one dominant conformer population was found. This conformer is characterized by a nearly trans orientation of the CH and NH hydrogens of both acetamido groups. This finding is in perfect agreement with x‐ray crystallographic data on the solid state conformation of the 1‐N‐acetyl‐ and 1‐N‐(β‐aspartoyl)‐2‐acetamido‐2‐deoxy‐β‐D‐glucopyranosylamine. The precise identification of this dominant conformer of N‐glycopeptides in solution was the major question addressed herein by the structural analyses. A “CD additivity” experiment was carried out using an equimolar solution of Boc‐Pro‐Asp‐NHCH3 and l‐N‐acetyl‐3,4,6‐tri‐O‐acetyl‐2‐acetamido‐2‐deoxy‐β‐D‐gluco‐pyranosylamine at ambient temperature in acetonitrile. The CD spectrum obtained from the equimolar solution of the above two molecules (the “spectroscopic sum”) was identical with the CD curve obtained from the algebraic summation of the individually recorded CD spectra of the peptide and the carbohydrate moiety (“mathematical sum”).

The global picture of the CD spectral analyses of the eight parent peptides with the eight N‐glycopeptides revealed that in trifluoroethanol and acetonitrile, the side‐chain modification of the Asn models (natural N‐glycopeptide analogues) by N‐glycosylation has a significant effect on the conformation of the carrier peptide, resulting in a decrease in the original type I β‐turn content. Simultaneously, the type II β‐turn conformational percentage increased to ≈ 20%. Such a conformational ratio change seems to be larger than the expected errors arising from the CD analyses, and agrees with the results of MD calculations. N‐glycosylation of Asn residues causes perturbations, not only through the covalent bond, but also through specific hydrogen bonds between the backbone and side chain atoms. CD spectroscopy, augmented by efficient CD curve deconvolution techniques, has proved to be a useful tool for studying multicomponent conformer mixtures of small linear peptides in solution and changes of conformational equilibria caused by N‐glycosylation. © 1993 John Wiley & Sons, Inc.
Sol–gel transition of alginate solution by the addition of various divalent cations: 13C‐nmr spectroscopic study
Authors: Wang Zheng‐Yu , Zhang Qinc‐Zhi , Konno Mikio , Saito Shozaburo
Published: December 2004

13C‐NMR spectroscopic studies have been made on alginate solutions undergoing sol–gel transition induced by four different divalent cations: Ca, Cu, Co, and Mn. From the analysis of nmr spectra and relaxation times, we have found different interaction modes existing between the Ca–alginate systems and the transition metal (Cu, Co, and Mn)–alginate systems. In the Ca–alginate systems, there exists a specific interaction characterized by a strong autocooperative binding between guluronate residues and calcium ions, and all functional groups in guluronate residues are considered to involve the interaction with calcium ions. On the other hand, in transition metal (Cu, Co, and Mn)–alginate systems, sol–gel transition is characterized by a complex formation in which the carboxyl groups in both mannuronate and guluronate residues are coordinated to metal ions. The other functional groups, like hydroxyl groups, do not participate in the binding to metal ions. It is suggested by relaxation time measurements that from a microscopic point of view the sol–gel transition phenomena can be explained as a dynamic process in which the low frequency molecular motions are dominant and increase their proportions with the formation of three‐dimensional cross‐links. © 1993 John Wiley & Sons, Inc.
Unfolding of an α‐helix in peptide crystals by solvation: Conformational fragility in a heptapeptide
Authors: Karle Isabella L. , Flippen‐Anderson Judith L. , Uma K. , Balaram P.
Published: December 2004

The structure of the peptide Boc‐Val‐Ala‐Leu‐Aib‐Val‐Ala‐Leu‐OMe has been determined in crystals obtained from a dimethylsulfoxide–isopropanol mixture. Crystal parameters are as follows: C38H69N7O10 · H2O · 2C3H7OH, space group P21, a = 10.350 (2) Å, b = 26.084 (4) Å, c = 10.395(2) Å, β = 96.87(12), Z = 2, R = 8.7% for 2686 reflections observed > 3.0 σ (F). A single 5 → 1 hydrogen bond is observed at the N‐terminus, while two 4 → 1 hydrogen bonds characteristic of a 310‐helix are seen in the central segment. The C‐terminus residues, Ala(6) and Leu(7) are expended, while Val(5) is considerably distorted from a helical conformation. Two isopropanol molecules make hydrogen bonds to the C‐terminal segment, while a water molecule interacts with the N‐terminus. The structure is in contrast to that obtained for the same peptide in crystals from methanol‐water [ I. L. Karle, J. L. Flippen‐Anderson, K. Uma, and P. Balaram (1990) Proteins: Structure, Function and Genetics, Vol. 7, pp. 62–73] in which two independent molecules reveal an almost perfect α‐helix and a helix penetrated by a water molecule. A comparison of the three structures provides a snapshot of the progressive effects of solvation leading to helix unwinding. The fragility of the heptapeptide helix in solution is demonstrated by nmr studies in CDC13 and (CD3)2SO. A helical conformation is supported in the apolar solvent CDCl3, whereas almost complete unfolding is observed in the strongly solvating medium (CD3)2SO. © 1993 John Wiley & Sons, Inc.
Probing protein structure by solvent perturbation of nmr spectra. II. Determination of surface and buried residues in homologous proteins
Authors: Esposito Gennaro , Lesk Arthur M. , Molinari Henriette , Motta Andrea , Niccolai Neri , Pastore Annalisa
Published: December 2004

The experimental assignment of most residues in a protein to the surface or interior is in principle possible without prior solution of a complete three‐dimensional structure. The method described is based on nmr measurements that determine the amino acid composition of the surface of a protein [A. Petros, L. Mueller, and K. D. Kopple (1990) Biochemistry, Vol. 29, pp. 10041–10048; G. Esposito, A. M. Lesk, H. Molinari, A. Motta, N. Niccolai, and A. Pastore (1992) Journal of Molecular Biology, Vol. 224, pp. 659–670]. If these measurements are carried out on several homologous proteins of known sequence, it is possible to combine the results to determine, in most cases, which positions in the sequence contain exposed residues. © 1993 John Wiley & Sons, Inc.
Conformational requirements for molecular recognition of acetylcholine receptor main immunogenic region (MIR) analogues by monoclonal anti‐MIR antibody: A two‐dimensional nuclear magnetic resonance and molecular dynamics approach
Authors: Tsikaris Vassilios , Detsikas Evangelos , Sakarellos‐Daitsiotis Maria , Sakarellos Constantinos , Vatzaki Efstratia , Tzartos Socrates J. , Marraud Michel , Cung Manh Thong
Published: December 2004

The conformational properties of two [D‐A70, A76] and [Aib70, A76] analogues of the α67–76 Torpedo acetylcholine receptor fragment, with low binding capacity for the anti main immunogenic region (MIR) antibodies, were studied in DMSO by two‐dimensional nmr techniques and molecular dynamics simulations. The results were compared to the free and bound conformations of the [A76] analogue, which has twice more affinity for the anti‐MIR monoclonal antibody 6 (mAb6), than the natural Torpedo sequence. It appeared that a single substitution of the A70, at a crucial position, by the D‐A70 or Aib70, could modify completely the conformational behavior of the peptide and reduced its recognition by the anti‐MIR antibody. The WNPADY rigid structure at the N‐terminal part was essential for antibody recognition. The adjacent more flexible C‐terminal sequence (GGIK) gives additional stability to the monoclonal antibody–peptide complex probably due to an adequate orientation of the peptide side chains in the complex, by setting them in close contact with the antibody. © 1993 John Wiley & Sons, Inc.
Molecular dynamics simulation of the stability of a 22‐residue α‐helix in water and 30% trifluoroethanol
Authors: Van Buuren Aldert R. , Berendsen Herman J. C.
Published: December 2004

A molecular dynamics (MD) simulation was performed on the α‐helix H8‐HC5, the C‐terminal part of myoglobin (residue 132–153), under periodic boundary conditions in two different solutions, water and water with 30% (v/v) 2,2,2‐trifluoroethanol (TFE), at 300 K to investigate the stability of the helix. In both simulations, the initial configuration was a canonical right‐handed α‐helix. In the course of the MD trajectory in water (200 ps), the helix clearly destabilized and began to unfold after 100 ps. In the TFE solution, two stable parts of helical regions were observed after 70 ps of a 200‐ps MD simulation, supporting the notion that TFE acts as a structure‐forming solvent. © 1993 John Wiley & Sons, Inc.
The solution conformation Ac‐Pen‐Arg‐Gly‐Asp‐Cys‐OH, a potent fibrinogen receptor antagonist
Authors: Bogusky Michael J. , Naylor Adel M. , Mertzman Michael E. , Pitzenberger Steven M. , Nutt Ruth F. , Brady Stephen F. , Colton Christiane D. , Veber Daniel F.
Published: December 2004

The solution conformation of , a potent fibrinogen receptor antagonist, was characterized in DMSO‐d6 by the combination of nmr and molecular modeling. The conformational space available to the peptide was explored using a distance geometry algorithm with distance constraints derived from 1H‐nmr spectra. The dynamics of the peptide were examined by relaxation time measurements and low temperature studies. The results from the low temperature studies suggest that the peptide backbone does not exist in a single, well‐defined conformation but undergoes exchange between multiple conformers. This result is consistent with the inability to find a single structure that satisfies all the nmr‐derived constraints. The constraints could only be satisfied by considering pairs of conformers to represent the experimental data. The low energy conformers comprise type II′ or type V β‐turns with distinct side‐chain directionality. The Arg‐Gly‐Asp portion of the ring is flexible and can be described by amide‐plane rotations of the Arg‐Gly and Gly‐Asp peptide bonds. Although some backbone flexibility is evident, the incorporation of β,β‐dimethyl cysteine imparted greater conformational rigidity as compared to the previously studied cyclic pentapeptide, . © 1993 John Wiley & Sons, Inc.
Molecular recognition of watson–crick base‐pair reversals in triple‐helix formation: Use of nonnatural oligonucleotide bases
Authors: Mohan V. , Cheng Y.‐K. , Marlow Gail E. , Pettitt B. Montgomery
Published: December 2004

We report the calculated characteristics of nonnatural triplex‐forming oligonucleotide (TFO) bases recognizing base‐pair reversals (TA → AT) in a double‐helical DNA sequence. Ab initio and molecular mechanics calculations have been carried out to characterize the geometric and energetic consequences at the base‐pair reversal sites. We have estimated the free energies of solvation of the natural and proposed bases by solving the linearized Poisson–Boltzmann equation. The calculations indicate that the proposed TFO bases should bind with some specificity to the duplex. Implications of the strategy used in the context of molecular biology is discussed. © 1993 John Wiley & Sons, Inc.
Individual‐site binding data and the energetics of protein–DNA interactions
Authors: Saroff Harry A.
Published: December 2004

Individual‐site isotherms for the binding of bacteriophage λ repressor to the left and right λ operators have been determined [D. F. Senear, M. Brenowitz, M. A. Shea, and G. K. Ackers (1986) Biochemistry, Vol. 25, pp. 7344–7354.] using the DNAse protection technique [ footprinting; D. J. Galas and A. Schmitz (1978) Nucleic Acids Research, Vol. 5, pp. 3157–3170]. These extensive data have been interpreted with a quantitative model that emphasized cooperative interactions between adjacently bound ligands [occupied ↔ occupied interactions; G. K. Ackers, A. D. Johnson, and M. A. Shea (1982) Proceedings of the National Academy of Science, USA, Vol. 79, pp. 1129–1133]. Overlooked in this model are the effects of cooperative interactions between a site containing a bound ligand and its neighboring unoccupied site (occupied ↔ unoccupied interactions). This paper reinterprets the existing data with a model that considers occupied ↔ unoccupied as well as occupied ↔ occupied interactions. The results yield parameters that differ substantially from those already reported. A discussion on the advisability of ignoring occupied ↔ unoccupied interactions is included. © 1993 John Wiley & Sons, Inc.
Chain length dependent transition of 310‐ to α‐helix of Boc‐(Ala‐Aib)n‐OMe
Authors: Otoda Kazuya , Kitagawa Yasuyuki , Kimura Shunsaku , Imanishi Yukio
Published: December 2004

An apolar synthetic octapeptide, Boc‐(Ala‐Aib)4‐OMe, was crystallized in the triclinic space group P1 with cell dimensions a = 11.558 Å, b = 11.643 Å, c = 9.650 Å, α = 120.220°, β = 107.000°, γ = 90.430°, V = 1055.889 Å3, Z = 1, C34H60O11N8·H2O. The calculated crystal density was 1.217 g/cm3 and the absorption coefficient ϕ was 6.1. All the intrahelical hydrogen bonds are of the 310 type, but the torsion angles, ϕ and ψ, of Ala(5) and Ala(7) deviate from the standard values. The distortion of the 310‐helix at the C‐terminal half is due to accommodation of the bulky Boc group of an adjacent peptide in the nacking. A water molecule is held between the N‐terminal of one peptide and the C‐terminal of the other. The oxygen atom of water forms hydrogen bonds with N (1) ‐H and N (2) ‐H, which are not involved in the intrahelical hydrogen bonds. The hydrogen atoms of water also formed hydrogen bonds with carbonyl oxygens of the adjacent peptide molecule. On the other hand, 1H‐nmr analysis revealed that the octapeptide took an α‐helical structure in a CD3CN solution. The longer peptides, Boc‐(Ala‐Aib)6‐OMe and Boc‐(Ala‐Aib)8‐OMe, were also shown to take an α‐helical structure in a CD3CN solution. An α‐helical conformation of the hexadecapeptide in the solid state was suggested by x‐ray analysis of the crystalline structure. Thus, the critical length for transition from the 310‐ to α‐helix of Boc‐(Ala‐Aib)n‐OMe is 8. © 1993 John Wiley & Sons, Inc.
An NMR and conformational investigation of the trans‐syn cyclobutane photodimers of dTpdU
Authors: Tabaczynski Walter A. , Lemaire Danielle G. E. , Ruzsicska Bŕla P. , Alderfer James L.
Published: December 2004

Two trans‐syn cyclobutane photodimers of thymidylyl (3′–5′) deoxyuridine were formed by deamination of the corresponding trans‐syn cyclobutane photodimers of thymidylyl(3′–5′) deoxycytidine and were examined by 1H−, 13C−, and 31P‐nmr spectroscopy. Correlation spectroscopy, nuclear Overhauser enhancement spectroscopy, and one‐dimensional heterodecoupling experiments allowed a more complete assignment of the 1H spectra, compared with previous reports by Koning et al. [ (1991) European Journal of Biochemistry, Vol. 195, pp. 29–40] and Liu and Yang [(1978) Biochemistry, Vol. 17, pp. 4865–4876]. Deoxyribose ring conformations were calculated from 1H coupling constants by pseudorotational analysis, and rotamer distributions of exocyclic bonds were calculated from the observed homonuclear and heteronuclear coupling constants. The cyclobutane ring configuration (CB) of each isomer was identified, using arguments based upon observed scalar and dipolar couplings. Glycosidic bond conformation was ascertained from nuclear Overhauser enhancements observed between base and deoxyribose protons. Isomer I (S‐type class; CB−; SYN‐ANTI) and isomer II (N‐type class; CB+; ANTI‐SYN) exhibit markedly different conformational features. 31P chemical shifts and exocyclic bond rotamer distributions indicate diminished backbone flexibility for both photoproducts relative to parent thymidylyl (3′–5′) deoxyuridine. Isomer I (SYN‐ANTI) is particularly rigid, while isomer II (ANTI‐S YN) maintains some flexibility. Also, 13C spectra were acquired and assigned unequivocally with the aid of short‐ and long‐range two‐dimensional heteronuclear shift correlation experiments. © 1993 John Wiley & Sons, Inc.
Formation of several stable complexes between the minor components of the cyclic tetrapeptide cyclo‐(‐Pro1‐Ala2‐D‐Phe3‐Leu4‐) and some specific Boc‐amino acids
Authors: McEwen I. , Ottosson K.
Published: December 2004

The cyclic tetrapeptide cyclo(‐Pro1‐Ala2‐D‐Phe3‐Leu4‐) was modeled and synthesized to be used for molecular interactions and chiral discrimination studies in CDCl3. Total correlation spectroscopy and nuclear Overhauser effect spectroscopy spectra of the cyclic tetrapeptide showed the presence of one dominant stereoisomer—1—and three minor ones— 2a, 2b, and 2c—in a relationship of 92:6:1:1. They formed three‐ to five‐hydrogen bond complexes with Boc‐D‐Ser, Boc‐L‐Ser and Boc‐L‐Thr (Boc: t‐butyloxylcarbonyl). These three Boc‐amino acids interact more strongly with 2a, 2b, and 2c than with 1, altering their relative concentrations to 48:40:6:6. In the complex between the cyclic tetrapeptide and Boc‐D‐Ser, the stereoisomer 2a exchanged chemically with 1, 2b, and 2c, while 1 did not exchange with either 2b or 2c. This chemical exchange is due to cis‐trans isomerization of the peptide bonds. The chiral discrimination of 2a, 2b, and 2c was stronger than that of 1. No complexation occurred with Boc‐L‐Ala or Boc‐L‐Trp. © 1993 John Wiley & Sons, Inc.
Quinacrine: Spectroscopic properties and interactions with polynucleotides
Authors: Doglia S. M. , Albinsson B. , Hiort C. , Nordén B. , Gräslund A.
Published: December 2004

The acridine dye quinacrine and its interactions with calf thymus DNA, poly(dA‐dT) · poly (dA‐dT), and poly (dG‐dC) · poly(dG‐dC) were studied by light absorption, linear dichroism, and fluorescence spectroscopy. The transition moments of quinacrine give rise to absorption bands polarized along the short axis (400–480‐nm band), and the long axis (345‐nm and 290‐nm bands) of the molecule, respectively. Linear dichroism studies show that quinacrine intercalates into calf thymus DNA as well as into the polynucleotides, displaying fairly homogeneous binding to poly (dA‐dT) · poly (dA‐dT), but more than one type of intercalation site for calf thymus DNA and poly (dG‐dC) · poly(dG‐dC). Fluorescence spectroscopy shows that for free quinacrine the pK = 8.1 between the mono‐ and diprotonated states also remains unchanged in the excited state. Quinacrine bound to calf thymus DNA and polynucleotides exhibits light absorption typical for the intercalated diprotonated form. The fluorescence enhancement of quinacrine bound to poly (dA‐dT) · poly(dA‐dT) may be due to shielding from water interactions involving transient H‐bond formation. The fluorescence quenching in poly(dG‐dC) · poly(dG‐dC) may be due to excited state electron transfer from guanine to quinacrine. © 1993 John Wiley & Sons, Inc.
Photoresponsive polypeptides: Photochromism and conformation of poly (L‐glutamic acid) containing spiropyran units
Authors: Fissi A. , Pieroni O. , Ciardelli F. , Fabbri D. , Ruggeri C. , Umezawa K.
Published: December 2004

Spirobenzopyran units were bound to the side chains of poly (L‐glutamic acid) and partially methylated poly(L‐glutamate)s. The modified polymers were found to exhibit “reverse photochromism” in hexafluoro‐2‐propanol (HFP), so the samples kept in the dark were characterized by an intense absorption band in the visible range of the spectrum, which was completely erased upon exposure to sunlight or irradiation at 500–550 nm.

The CD spectra showed that the macromolecules adopted a random coil conformation in the dark, whereas the bleached solutions after exposure to light displayed the typical CD pattern of the α‐helix. The back reaction in the dark was accompanied by the progressive decrease of the helix content and recovery of the original disordered conformation. The photoinduced conformational changes resulted in large and reversible viscosity variations.

When spiropyran side chains were converted to “spiropyran salts” of trifluoroacetic acid, the system was still photochromic, but the macromolecules were disordered both in the dark and light conditions. However, when appropriate amounts of methanol were added as a cosolvent to the HFP solutions, the system responded to light, giving reversible variations of the α‐helix content. Irradiation at appropriate solvent compositions allowed modulation of the extent of the photoresponse. © 1993 John Wiley & Sons, Inc.
A and Z canonical conformations in d(CnGCGn) crystals characterized by microFTIR and microRaman spectroscopies
Authors: Sfihi H. , Liquier J. , Urpi L , Verdaguer N. , Subirana J. A. , Igolen J. , Taillandier E.
Published: December 2004

Two crystals d(C2GCG2) and d(C5GCG5) have been studied under microscope by Fourier transform ir spectroscopy and Raman spectroscopy. The x‐ray diffraction study of the latter crystal had shown that the d(C5GCG5) sequence is the first DNA dodecamer known to adopt a canonical A conformation [N. Verdaguer, J. Aymami, D. Fernandez‐Forner, I. Fita, M. Coll, T. Huynh‐Dinh, J. Igolen, and J. A. Subirana (1991) Journal of Molecular Biology, Vol. 221, pp. 623–635]. Characteristic ir marker bands and Raman marker peaks of the A conformation have thus been obtained and are compared with previously proposed assignments correlated to fiber diffraction x‐ray results obtained on polymers. The d(C2GCG2) sequence crystal had previously been studied in an intermediate form between B and Z [L. Urpi, J. P. Ridoux, J. Liquier, N. Verdagner, I. Fita, J. A. Subirana, F. Iglesias, T. Huynh‐Dinh, J. Igolen, and E. Taillandier (1989) Nucleic Acids Research, Vol. 17, pp. 6669–6679]. In this paper we present results obtained from a crystal with this oligonucleotide in Z conformation. The effect of the crystallization conditions on the geometry of the obtained oligomer helix is discussed. The influence of the addition, to the central tetramer CGCG, of dCn stretches (at the 5′ end) and dGn stretches (at the 3′ end) of different lengths, on the conformational flexibility of the nucleic acid, is considered. © 1993 John Wiley & Sons, Inc.