bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of a new electronic transition in the Z form of poly(dG‐dC)·poly(dG‐dc) by infrared absorption and resonance Raman spectroscopy
Authors: Chinsky L. , Jolles B. , Laigle A. , Turpin P. Y. , Taboury J. , Taillandier E.
Published: May 2005

Infrared absorption and resonance Raman spectroscopy (RRS) are used to study poly(dG‐dC)·poly(dG‐dC) in two different forms: the right‐handed B form at low ionic strength and the left‐handed Z form at high ionic strength. The existence of a new electronic absorption band in the 290–300‐nm region is evidenced by uv RRS studies of the Z form at different wavelengths of excitation. Infrared absorption spectra prove that this new electronic band is polarized perpendicularly to the cytosine plane. The possibility of a nπ* character of this transition moment is discussed.
Theoretical studies on the conformation of saccharides. VIII. Solvent effect on the stability of β‐cellobiose conformers
Authors: Tvaroška Igor
Published: May 2005

The conformational equilibria of five β‐cellobiose conformers have been studied theoretically in 10 solvents. The stability of the conformers in dilute solution has been compared by using the method that has already been tested for 2‐methoxytetrahydropyran, β‐maltose, and D‐glucose. The solvation energy consists of electrostatic, dispersion, and cavity terms which have been determined from the properties of the solute calculated by the PCILO quantum‐chemical method and physicochemical properties of the solvents. The calculated abundance of conformers depends on the solvent (e.g., in dioxane C1:C2:C3:C4:C5 = 60.0:34.1:2.9:2.0:1.0; in dimethylsulfoxide, 75.5:22.1:1.8:0.5:0.2; and in water, 82.2:16.2:1.3:0.2:0.1). The results obtained indicate that the preponderant conformer in the aqueous solution is similar to the one adopted by β‐cellobiose in the crystalline form. The role of individual contributions to the solvation energy have been analyzed. Based on the determined abundance of conformers, averaged residual optical activity and nmr parameters have been calculated and compared with observable properties. The marked differences observed between solvent‐induced conformational changes for β‐cellobiose and β‐maltose have been discussed from the viewpoint of the solubility of the cellulose.
Molecular theory of the helix–coil transition in polyamino acids. V. Explanation of the different conformational behavior of valine, isoleucine, and leucine in aqueous solution
Authors: Gō Mitiko , Scheraga Harold A.
Published: May 2005

Even though poly(L‐valine) and poly(L‐isoleucine) both contain residues that are branched at their β‐carbon atoms, they exhibit a different behavior of their Zimm‐Bragg helix‐growth parameter s in aqueous solution. This quantity increases with temperature for poly(L‐valine) but decreases for poly(L‐isoleucine). The origin of this behavioral difference was examined by computing theoretical values of s versus temperature from interatomic interaction energies, taking solvent (hydrophobic and hydrophilic) effects into account. The calculated s versus temperature curves for both homopolymers are consistent with the observed experimental behavior. The two homopolymers behave differently because of differences in the change in the number of hydration‐shell water molecules accompanying their helix–coil transitions. The larger isoleucine side chains are more crowded together in both the α‐helical and coil forms than are those of valine. Therefore, there is a smaller change in hydration of the isoleucine side chains compared to that of the valine side chains in the helix–coil transition. By analyzing the effects of hydration on the s versus temperature curves, it is possible to account also for the experimental curve for poly(L‐leucine), which exhibits an intermediate behavior between those for poly(L‐valine) and poly(L‐isoleucine).
Theoretical studies on protein–nucleic acid interactions. III. Stacking of aromatic amino acids with bases and base pairs of nucleic acids
Authors: Kumar N. Vasant , Govil Girjesh
Published: May 2005

Stacking of aromatic amino acids tryptophan (Trp), tyrosine (Tyr), phenylalanine (Phe), and histidine (His) with bases and base pairs of nucleic acids has been studied. Stacking energies of the amino acid–base (or base pair) complexes have been calculated by second‐order perturbation theory. Our results show that, in general, the predominant contribution to the total stacking energy comes from the dispersion terms. In these cases, repulsion energy is greater than the sum of electrostatic and polarization energies. In contrast to this, interaction of histidine with the bases and base pairs is largely Coulombic in nature. The complexes of guanine with aromatic amino acids are more stable than the corresponding complexes of adenine. Among pyrimidines, cytosine forms the most stable complexes with the aromatic amino acids. The G · C base pair has the highest affinity with aromatic amino acids among various sets of base pairs. Optimized geometries of the stacked complexes show that the aromatic moieties overlap only partially. The heteroatom of one residue generally overlaps with the other aromatic moiety. There is a considerable degree of configurational freedom in the stacked geometries. The role of stacking in specific recognition of base sequences by proteins is discussed.
Resonance Raman spectra of mononucleotides obtained with 266 and 213 nm ultraviolet radiation
Authors: Ziegler L. D. , Hudson B. , Strommen D. P. , Peticolas W. L.
Published: May 2005

Resonance Raman spectra of the nucleoside 5′‐monophosphates UMP, CMP, AMP, and GMP have been obtained with 266‐ and 213‐nm radiation, the fourth and fifth harmonics of a Nd:YAG laser. The 266‐nm radiation is resonant with the states giving rise to the first absorption band of the bases. The resulting spectra are in agreement with those reported previously using similar wavelength excitation but are generally of better quality. The 213‐nm radiation is resonant with those states giving rise to the second strong absorption band of the bases. The spectra obtained with this wavelength show several new features relative to the 266‐nm spectra, including strong enhancement of modes of the pyrimidines with a character similar to the e2g ν8 mode of benzene, relative enhancement of ring modes at 1580 and 729 cm−1 in AMP, and strong enhancement of the 1670‐cm−1 C = O mode of GMP. These enhancements are discussed in terms of previously reported preresonance behavior and predicted intensities based on CNDO bond‐order changes and normal‐mode calculations. The results of a preliminary study of the effect of the interaction of GMP with cis‐dichlorodiammineplatinum(II) on the 213‐nm resonance Raman spectrum is also discussed.
Transfer of peptide hormones from aqueous to membrane phases
Authors: Deber Charles M. , Behnam Basil A.
Published: May 2005

Peptide hormones and neurotransmitters are functional amphiphilic substances that deploy their chared and nonpolar substituents as required for traversing aqueous phases en rout to their ultimate transfer into the lipid‐rich environment of their membrane‐embedded receptors. As a means of determining the role(s)that cellular membrane lipids may play in mediating these events, we describe an experimental approach, using high‐resolution 1H‐and 13C‐nmr spectroscopy, for delineation of the structures of complexes between the (neurotransmitter pentapeptide) enkephalins and micellar and vesicular phospholipid particles. Residue‐specific enkephalin interactions with lipid are identified; affinity constants for the hydrophobic component(s) of peptide/lipid association are calculated for enkephalin and several of its analogs; and comparisons with morphine are presented. Finally, based on molecular details obtained from nmr experiments, a model is proposed for the encoutner of a peptide hormone with a phospholipid membrane surface.
Peptide homologs, isosteres, and isomers: A general approach to structure–activity relationships
Authors: Goodman Murray
Published: May 2005

A general approach to study peptide structure is presented using three areas of ongoing research in our laboratories. The first involves the molecular basis for taste of peptide derivatives. We synthesized dipeptides based on L‐aspartyl‐α‐aminocycloalkane carboxylic acid methyl ester. A homologous series of cycloalkane derivatives was studied. The cyclopropane, cyclobutane, and cyclopentane derivatives are sweet, the cyclohexane and cycloheptane peptides are bitter, and the cyclooctane homolog is tasteless. The related acyclic analog L‐aspartyl‐aminoisobutyric acid methyl ester is sweet, while the L‐aspartyl diethyl glycine carboxylic acid methyl ester is tasteless. A model is presented to explain these experimental observations. The second area involves depsipeptides as isosteric replacements of α‐hydroxy acids for amino acid residues in peptide chains. We have synthesized sequentially defined polydepsipeptides as model systems for polypeptides. A detailed analysis of the conformational order for these polydepsipeptides is presented. The third area involves partial retro–inverso peptide modifications of isomeric cyclic enkephalin analogs, which illustrate the relationship between the modification and biological activity. We are probing the intramolecular hydrogen‐bonding features for these biologically active molecules. From such findings we are relating the structural and conformational preferences deduced from spectroscopy and molecular mechanics to biological activity.
Time scale, geometrical constraints, and disulfide bond formation in the folding of small globular proteins
Authors: Gałat Andrzej
Published: May 2005

We hypothesize a model of protein folding based on the Poincaré recursion argument and a number of experimental results, including CD, nmr, and Raman spectra. Our model considers that protein folding in vivo proceeds through prefolded peptide segments consisting of 3 to 14 amino acid residues. Such segments may fold spontaneously into nativelike microdomains within a biologically feasible time, i.e., in the 10−6–10−1 s time scale. If, due to improper recognition and adjustment of their surfaces, these transiently formed secondary structures are not stabilized by long‐range interactions, then the protein species occur within a time‐ and number‐averaged spectrum of populations of transient conformational substates until the final, proper adjustment of the segments takes place. However, if, during protein folding, incorrect disulfide (S‐S) bonds are formed, then such unique through‐space contacts between the different parts of the polypeptide chain are usually restricted to a minimum. It is postulated that unfolding and refolding processes in vitro, and protein folding in vivo, proceed through variably populated quantized substates. The distribution of these substates depends on a number of molecular interactions between the phase and the hydration spheres surrounding the prefolded surfaces of peptide segments and long‐range interactions between these prefolded surfaces.
Rheological studies of creep and creep recovery of unligated fibrin clots: Comparison of clots prepared with thrombin and ancrod
Authors: Bale Marsha D. , Müller Michael F. , Ferry John D.
Published: May 2005

Mechanical creep and creep recovery in small shearing deformations have been studied in unligated clots formed with both thrombin and ancrod. In thrombin clots, both A binding sites (which interact with “a” sites to link monomer units within a protofibril) and B sites (which interact with “b” sites to form links between protofibrils) are exposed to enable formation of linkages; in ancrod clots, only the A sites are exposed. Fine clots (with minimal lateral aggregation of protofibrils), coarse clots (with substantial aggregation of fibril bundles), and clots of intermediate coarseness were compared. Fine thrombin clots showed less creep at short times but more creep at long times than coarse or intermediate clots and had more irrecoverable deformation relative to the initial elastic deformation. Ancrod clots had greater irrecoverable deformation than the corresponding thrombin clots, both fine and coarse. The permanent deformation in fine ancrod clots was enormous, corresponding almost to fluid character; the rate of permanent deformation was larger than that in fine thrombin clots by more than two orders of magnitude. For all types of clots, differential measurements of compliance (or its reciprocal, elastic modulus), as well as the applicability of the Boltzmann superposition principle to calculation of creep recovery, showed that the overall density of structure remained constant throughout the mechanical history; i.e., if structural elements were breaking, they were reforming at the same rate in different configurations. The possibility that the weakness of ancrod clots is attributable to partial degradation of α‐chains rather than absence of Bb linkages was eliminated by comparisons of clots made with thrombin, ancrod, and ancrod plus thrombin; the last two showed identical partial degradation of α‐chains (by gel electrophoresis), but the first and third had essentially identical initial elastic moduli and creep behavior. Two alternative mechanisms for irrecoverable deformation in fine clots are discussed, involving rupture of protofibrils and slippage of twisted segments, respectively.
Role of interstrand loops in the formation of intramolecular cross‐β‐sheets by homopolymino acids
Authors: Mattice Wayne L. , Scheraga Harold A.
Published: May 2005

A matrix treatment of the formation of intramolecular anti‐parallel β‐sheets from a statistical coil has been extended to incorporate interstrand loops of arbitrary size. The behavior of the model is compared with a simpler version in which all pairs of contiguous strands were connected by β‐bends. When large interstrand loops are allowed, there are many more types of sheets than is the case when all contiguous strands must be connected by tight or β‐bends. For this reason, the larger interstrand loops make it easier to introduce the initial sheet into a statistical coil, and the sheet content is enhanced in the early stages of stages of sheet formation (i.e., at small values of the growth parameter t). As the transition continues (i.e., as t increases), a stage will be reached where occupancy of the statistical coil state is negligible because nearly all residues are in sheets or interstrand loops. Now, additional sheet formation can be accomplished only at the expense of residues in the interior of interstrand loops. For this reason, the larger interstrand loops make it more difficult to complete the final stages of sheet formation. These effects are especially dramatic in the formation of cross‐β‐sheets.
Crystal structure of dehydromonopetide, (Z)‐N‐acetyl‐α,β‐dehydrophenylalanine methylamide
Authors: Aubry A. , Allier F. , Boussard G. , Marraud M.
Published: May 2005

The crystal structure of (Z)‐acetyl‐α,β‐dehydrophenylalanine methylamide (monoclinic Cc, a = 10.241(1), b = 15.252(1), c = 8.643(1) Å, β = 120.98(1)°, Z = 4) has been solved by x‐ray diffraction to an R‐factor = 0.148, and compared to that of the homologous L‐phenylalanine dervative. Molecules are intermolecularly hydrogen‐bonded to four neighboring molecules in a three‐dimensional network with alternating layers of interacting amide bonds and orthogonally arranged phenyl rings. The existence of the Cα = Cβ double bond results in a phenyl orientation that is forbidden for phenylananine (χ1 = −7,8°), and in shorter Cα − Cβ and Cβ − Cγ distances. The geometrical paramenters of the peptide backbone are not drastically modified by α,β‐unsaturation. However, the N‐Cα‐C′ angle is increased by nearly 5°, and the dimensions, and therefore probably the electronic conjugation, of the N‐terminal amide group to be affected by the occurrence of the vicinal Cα = Cβ double bond.
Conformational properties of gastrin fragments of increasing chain length
Authors: Peggion E. , Foffani M. T. , Wünsch E. , Moroder L. , Borin G. , Goodman M. , Mammi S.
Published: May 2005

The conformational properties of a series of biologically active gastrin peptides of increasing chain length have been investigated in TEE solution by spectroscopic techniques. It was found that elongation of the glutamic acid sequence from 1 to 5 residues at the N‐terminal portion of the molecules causes a cooperative change of the conformation of the peptide backbone. The environment of the biologically important C‐terminal sequence‐Trp‐Nle‐Asp‐Phe‐NH2 monitored by the near‐uv chiroptical propertical properties is alos affected by chain elongation. However, the change of the structure of the C‐terminal portion does not parallel the conformational change of the peptide backbone. In fact, the final folded structure at the C‐terminus is almost reached in the fragment with a sequence of 4 glutamic acid residues, while an additiona, relevent conformational change of the backbne is observed on further elongation of the chain to minigastrin and little gastrin. The ability of the fragments to fold into an ordered conformation on chain elongation parallels the increase of biolocical potency tested in vivo, reported in the literature, and suggests a correlation between these two facts. Ionization of the carboxyl side chains is without effect on the structure of the fragments with 2, 3, and 4 glutamic acid residues, while an effect is observed in minigastrin and little gastrin. From analysis of the CD properties and from their dependence upon side‐chain ionization a structural model is proposed for the hormones minigastrin and little gastrin. This tentative model includes a β‐bend located in the sequence Ala‐Tyr‐Gly‐Trp‐ and a short helical section at the N‐terminal portion of the hormones.
Dependence of purine 8C‐H exchange on nucleic acid conformation and base‐pairing geometry: A dynamic probe of DNA and RNA secondary structures
Authors: Benevides James M. , Thomas George J.
Published: May 2005

Laser Raman spectroscopy is employed as a probe of hydrogen isotope exchange in nucleic acids exhibiting different secondary structures. The rates for deuterium exchange of 8C‐H groups in adenine (A), hypoxanthine (I), and guanine (G) residues of ribo‐ and deoxyribopolynucleotides are compared with corresponding rates of mononucleotides. In general, nucleic acid secondary structure significantly retards the rate of purine 8C‐H exchange. Specifically, the exchange kinetics are strongly dependent on both the kind and amount of secondary structure. The retardation factor (R), defined as the quotient of rate constants for monomer and polymer exchanges, is greatest for the A‐helix (9.5 ± 1), intermediate for the B‐helix (2.8 ± 0.6), and smallest for the Z‐helix (1.5), thus permitting the three authenticated DNA structures to be distinguished from one another using the Raman dynamic probe. Polyribonucleotide complexes of the A‐helix family that contain the same backbone conformation and ribosyl pucker (C3′ ‐ endo/anti) but that differ in the geometry of base pairing or number of helix strands are also clearly distinguished by their different deuterium exchange rates. The extraordinarily large retardation of 8C‐H exchange (R > 200) that occurs in multihelical structures is attributed to hydrogen bonding by the purine 7N acceptor. These results indicate that 8C‐H exchange may be exploited to detect Hoogsteen base pairing and possibly interactions of nucleic acid‐binding proteins that involve the 7N site as hydrogen‐bond acceptor. The feasibility of the method for evaluation of solvent penetration to encapsidated genomes of DNA and RNA viruses is considered. The present results also reveal a number of new vibrational band assignments for identification of DNA and RNA secondary structures from equilibrium Raman spectra.
Kinetics of coil to α‐helix to β‐structure transitions of poly(L‐ornithine) in low concentrations of sodium dodecyl sulfate
Authors: Takeda Kunio
Published: May 2005

Conformational changes of poly(L‐ornithine) [(Orn)n] were studied in a sodium dodecyl sulfate (NaDodSO4) solution by CD. (Orn)n adopted an unstable and a stable helical structure below and above the NaDodSO4 concentration range where β‐structure was favored, respectively. CD stopped‐flow was used to monitor the transitions from coil to the unstable helix, from the helix to β‐structure, and from coil to β‐structure. Only the rate of the helix to β‐structure transition was accelerated by an increase in NaDodSO4 concentration, whereas the rates of the others were independent of NaDodSO4 concentration. The fractions of coil, α‐helix, and β‐structure in each conformation of (Orn)n caused by NaDodSO4 were computed by simulating a mixed spectrum of typical CD spectra for these structures to the experimentally obtained spectrum. The contents of the unstable and stable helical structures were less than 50 and 73%, respectively.
Aqueous solutions containing amino acids and peptides. Part 20. Volumetric behavior of some terminally substituted amino acids and peptides at 298.15 K
Authors: Leslie Tracy E. , Lilley Terence H.
Published: May 2005

The densities at 298.15 K of aqueous solutions containing some terminally substituted amino acids and peptides containing the glycyl, L‐and D‐alanyl, L‐leucyl, sarcosyl, and L‐prolyl residues have been dertermined and standard state partial molar volumes and volumetric pairwise virial coefficients obtained. It is shown that the partial molar volumes can be represented using group volume contributions, but this approach is only approximate, and significant effects of N‐terminal substitution and sequence dependence are observed. The volumetric virial coefficients for the amino acid amides have been expressed using a group‐additivity approach, and the results obtained indicate that the dominant contributions come from peptide group interactions with other peptide groups and with hydrophobic groups. There is also some evidence of both sequence and chiral effects on the volumetric virial coefficients for proline‐containing dipeptides.
Computer simulation of DNA supercoiling in a simple elastomechanical approximation
Authors: Šelepová Pavla , Kypr Jaroslav
Published: May 2005

DNA supercoiling is both an interesting problem from the theoretical point of view and an important phenomenon affecting DNA functions in vivo. Experimentally, however, hardly more than the overall hydrodynamic shape, superhelical density, and enzymic or chemical reactivity of the parameters that are in some way related to DNA secondary and tertiary structure in the superhelical state can be determined. Consequently, it is highly desirable to build up models of DNA supercoiling that, on the one hand, match the above type of global data and, on the other, take advantage of the knowledge about DNA structure at lower levels of complexity, i.e., with linear DNA molecules and its synthetic models. One possible approach, presented here, deals with an extension of Fuller's and Benham's general ideas concerning an elastomechanical model of DNA supercoiling. We extend their model with an algorithm suitable for numerical calculations and construct a fast computer program, ROPASE, that displays the rod shapes as dependent on its elastic properties and applied stress. Development of this program made inevitable a detailed analysis of the input parameters found to be degenerate in the sense that not all of them should be considered variable to generate the whole set of possible solutions of the model. Many calculations were performed using ROPASE to test its properties and the properties of the elastomechanical model. Representative DNA shapes are presented.
Conformational properties of Pro–Pro sequences. I. Crystal structures of two dipeptides with L‐Pro‐L‐Pro and L‐Pro‐D‐Pro sequences
Authors: Aubry André , Vitoux Bernard , Marraud Michel
Published: May 2005

The crystal structures of ButCO‐L‐Pro‐L‐Pro‐NHMe, H2O (1: monoclinic; P21; a = 6.662, b = 11.067, c = 12.205 Å; β = 96.28°) and ButCO‐L‐Pro‐D‐Pro‐NHMe (2: monoclinic; P21; a = 10.770, b = 15.039, c = 11.325 Å; β = 110.00°) have been solved by x‐ray diffraction. Structure 1 accommodates an open disposition with intermolecular interactions involving the water molecule, while 2 is βII‐folded by an intramolecular i + 3 → i hydrogen bond. In both derivatives, small thermal parameters are indicative of fairly fixed conformations for the proline rings. Comparison between conformations of either isolated or adjacent L‐Pro residues in the crystal structures of unstrained oligopeptides shows that the conformational properties of L‐Pro‐L‐Pro sequences are probably a simple combination of those found for isolated L‐Pro residues.
Prediction of the native conformation of a polypeptide by a statistical‐mechanical procedure. I. Backbone structure of enkephalin
Authors: Paine Gregory H. , Scheraga Harold A.
Published: May 2005

A new methodology for theoretically predicting the native, three‐dimensional structure of a polypeptide is presented. Based on equilibrium statistical mechanics, an algorithm has been designed to determine the probable conformation of a polypeptide by calculating conditional free‐energy maps for each residue of the macromolecule. The conditional free‐energy map of each residue is computed from a set of probability integrals, obtained by summing over the interaction energies of all pairs of nonbonded atoms of the whole molecule. By locating the region(s) of lowest free energy for each map, the probable conformation for each residue can be identified. The native structure of the polypeptide is assumed to be the combination of the probable conformations of the individual residues. All multidimensional probability integrals are evaluated by an adaptive Monte Carlo algorithm (SMAPPS—Statistical‐Mechanical Algorithm for Predicting Protein Structure). The Monte Carlo algorithm searches the entire conformational space, adjusting itself automatically to concentrate its sampling in regions where the magnitude of the integrand is largest (“importance sampling”). No assumptions are made about the native conformation. The only prior knowledge necessary for the prediction of the native conformation is the amino acid sequence of the polypeptide. To test the effectiveness of the algorithm, SMAPPS was applied to the prediction of the native conformation of the backbone of Met‐enkephalin, a pentapeptide. In the calculations, only the backbone dihedral angles (ϕ and ψ) were allowed to vary; all side‐chain (χ) and peptide‐bond (ω) dihedral angles were kept fixed at the values corresponding to the alleged global minimum energy previously determined by direct energy minimization. For each conformation generated randomly by the Monte Carlo algorithm, the total conformational energy of the polypeptide was obtained from established empirical potential energy functions. Solvent effects were not included in the computations. With this initial application of SMAPPS, three distinct low‐free‐energy β‐bend structures of Met‐enkephalin were found. In particular, one of the structures has a conformation remarkably similar to the one associated with the previously alleged global minimum energy. The two additional structures of the pentapeptide have conformational energies lower than the previously computed low‐energy structure. However, the Monte Carlo results are in agreement with an improved energy‐minimization procedure. These initial results on the backbone structure of Met‐enkephalin indicate that an equilibrium statistical‐mechanical procedure, coupled with an adaptive Monte Carlo algorithm, can overcome many of the problems associated with the standard methods of direct energy minimization.
Effect of salt on sodium polystyrene sulfonate measured by light scattering
Authors: Drifford Maurice , Dalbiez Jean‐Pierre
Published: May 2005

The quasielastic light scattering method was used to study the ionic strength dependence of the mutual diffusion coefficient of sodium polystyrene sulfonate (NaPSS) as a function of NaCl and CaCl2 concentrations. The results indicate a splitting in the relaxation times that depends on the ratio Cp/Cs, where Cp and Cs are the polyion and added salt concentrations. A universal relationship taking into account Manning's theory of condensation and the Debye screening due to the added salt is proposed to characterize the fast–slow relaxation time transition.
Theoretical study of the binding of aliphatic diamines to the minor groove of a B‐DNA (dA‐dT)11 oligomer
Authors: Gresh Nohad
Published: May 2005

Theoretical computations are performed on the binding of aliphatic diamines +H3N‐(CH2)n‐NH (n = 3–7), to the minor groove of a (dA‐dT)11 oligomer held in the B‐DNA conformation. The computations are performed in the framework of an additive procedure elaborated recently in this laboratory by means of which the intermolecular DNA–diamine interaction energies and the intramolecular energy variations of the diamine are computed simultaneously. The results of the computations show that the binding of the diamines occurs in well‐defined configurations in which each cationic extremity interacts with specific sites, O2(T), N3(A), and O1,(S) in the groove, the overall configuration differing according to the length of the diamine. The overall energy balance for complexation is found to depend on the chain length of the diamine, an optimal value for δE being found for 1,6 diaminohexane. This result is discussed in light of available experimental results of the compared affinities of diamines for the double‐stranded polymer dA‐dT.
Conformational analysis of cholecystokinin fragments CCK4, CCK5, and CCK6 by 1H‐nmr spectroscopy and fluorescence‐transfer measurements
Authors: Fournie‐Zaluski M. C. , Durieux C. , Lux B. , Belleney J. , Pham P. , Gerard D. , Roques B. P.
Published: May 2005

The confortmational behavior of the cholecystokinin‐related fragments CCK4, CCK5, and CCK6 as determined by 1H‐nmr spectroscopy in DMSO‐d6 and water and fluorescence‐transfer measurements in aqueous medium are greatly dependent on the ionization states of these peptides. Under netral conditions, the backbones of CCK5 and CCK6 preferentially adopted folded forms with a β‐turn including the four residues Gly‐Trp‐Met‐Asp, probably stabilized by a hydrogen bond between the CO of Gly and the NH of Phe. In these structures, possible induced by an ionic interaction between the carboxylic group of Asp32 and the NH group of the N‐terminal amino acid, the lateral chains of the various residues are quite distant from each other (15–16 Å). Under acidic conditions, extended structures without interactions between side chains predominate for CCK5 and CCK6, while for CCK4, a conformational change drawing the Trp and Phe side chains in close proximity was shown by fluorescence. The conformations observed in aqueous medium at physiological pH are discussed in relation to the biological activity of these peptides.
Flexibility and length of human bronchial mucin studied using low‐shear viscometry, birefringence relaxation analysis, and electron microscopy
Authors: Mikkelsen Arne , Stokke Bjørn Torger , Christensen Bjørn Erik , Elgsaeter Arnljot
Published: May 2005

The glycoprotein mucin was isolated from the sputum of patients with chronic obstructive bronchitis. The fractionation procedure included treatment with 6M urea at pH 12.5 followed by gel filtration in 6M urea at neutral pH. (1) Using a low‐shear Cartesian diver viscometer, we found that the mucin intrinsic viscosity equals (0.32 ± 0.03) L/g in 1000 mM NaCl solution increasing to (12 ± 3) L/g in 0.1 mM NaCl (pH 7 and 20°C). (2) The relaxation of electrically induced birefringence in mucin solutions was measured and the relaxation spectrum calculated using a Fourier‐transform deconvoltion method. We found that the dominant relaxation time increased from 1 to 150 μs when the exitation pulse duration used was increased from 2 to 300 μs. (3) Mucin was vacuum‐dried from glycerol‐containing solutions followed by low‐angle rotary shadowing and electron microscopy. Mucin was found to be unbranched, with contour lengths ranging from 300 to 2500 nm and with an average of 900 nm. Our result indicate that mucin is an extended and flexible molecule with Kuhn length 0.3–0.5% of the contour length.
Solid‐state conformation of some basic sequential polypeptides
Authors: Vives J. , Azorín F. , Subirana J. A. , Brack A. , Mayer R.
Published: May 2005

We have studied the structure of solid films obtained by x‐ray diffraction, from several basic polypeptides with a defined sequence. The alterating polypeptides poly(Ala‐Lys), poly(Leu‐Lys), poly(Val‐Lys), and poly(Arg‐Leu) all show a cross‐β‐structure in which layers of hydrophilic side chains alternate with layers containing hydrophobic side chains. The other polypeptides studied are not in the β‐conformation and appear to be in the α‐helical conformation. The helices obtained from poly(Lys‐Ala‐Ala) and poly(Lys‐Ala‐Ala‐Lys) appear to be packed in an unusual fashion, which favors interaction between alanine side chains. Such behavior is not found in poly(Lys‐Leu‐Ala).
Rotational dynamics of DNA from 10−10 to 10−5 seconds: Comparison of theory with optical experiments
Authors: Shibata John H. , Fujimoto Bryant S. , Schurr J. Michael
Published: May 2005

Optical anisotropy data spanning a very wide time range are analyzed using a recently developed theory for filamentous macromolecules that can bend, twist, and also admit overdamped local libration (or wobble) of the chromophore. A rapid relaxation in the fluorescence polarization anisotropy (FPA) near 10−10 s is fitted well by superimposing isotropic wobble of the chromophore (7° rms polar and azimuthal amplitude) on the long‐wavelength twisting and bending motions that characterize the relaxation at longer times but not by the latter alone. Moreover, the decay of the FPA from 0.5 to 150 ns cannot be satisfactorily fitted by chromophore wobble in an otherwise rigid DNA and must be assigned primarily to twisting, as noted previously.

Data from 26 ns to 20 μs for 600 base‐pair DNA are accurately fitted with only a single adjustable scaling factor when the tumbling correlation function is taken to be the empirical electric birefringence decay function of Elias and Eden. The Barkley‐Zimm (BZ) tumbling correlation for very long filaments appears to decay too rapidly and results in significant overestimation of the depolarization for t ≤ 300 ns. In the range of the FPA experiments (t ≥ 150 ns), equally good fits with equally uniform torsion constants are obtained for long DNAs, whether one assumes the BZ tumbling correlation function or neglects tumbling entirely, but the best‐fit torsion constant (actually the product of the torsion constant and friction factor) is increased by the factor 1.9 when the BZ result is used with a persistence length of a = 500 Å. The BZ bending theory is compared with other experimental data, and also with a simulation at very short times with mixed results. Present uncertainties regarding the tumbling dynamics and the friction factor for azimuthal rotation allow the torsion constant to be as much as 3.8 times larger than the initial estimate of Thomas et al. Apparent torsion constants obtained from relative ligase kinetics measurements are also briefly discussed.
Conformational studies on the bacterial cell wall peptide analog phenylacetyl‐D‐alanyl‐D‐alanine: Comparison between conformations of cell wall peptide analog and those of penicillin G
Authors: Labischinski H. , Barnickel G. , Naumann D. , Rönspeck W. , Bradaczek H.
Published: May 2005

The conformation of phenylacetyl‐D‐alanyl‐D‐alanine in the crystalline state was characterized by Fourier‐transform ir and Raman spectroscopy and was unambiguously solved by x‐ray single‐crystal determination. In the crystalline state, the molecule adopts a partially folded conformation quite similar to that of another cell wall peptide, acetyl‐D‐alanyl‐D‐alanine [Benedetti et al. (1981) J. Biol. Chem. 256, 9229–9234], although the crystal structure is stabilized by a quite different intermolecular hydrogen‐bond pattern. No significant deviation from the usual trans‐planar peptide group geometry was detected. The conformations accessible in the noncrystalline state were investigated by ir measurements in solution and conformational energy calculations. The theoretical study revealed that the peptide is a highly flexible molecule, since 55 minima were detected, within 3 kcal/mol, including the conformation found in the single crystal. The ir data for phenylacetyl‐D‐alanyl‐D‐alanine in different solvents were in accordance with virtually extended conformations, with some indication for weak, intramolecularly hydrogen‐bonded C5‐rings. These conformational data obtained for the cell wall peptide analog are compared with those known for penicillin G in the crystalline state.
Concentration dependence of proteoglycan diffusion
Authors: Harper Gregory S. , Comper Wayne D. , Preston Barry N. , Daivis Peter
Published: May 2005

The mutual diffusion coefficient of the bovine nasal cartilage proteoglycan subunit is found to increase rapidly with increasing concentration and decreasing ionic strength. These results have been obtained by analysis of the boundary relaxation of concentration gradients in the analytical ultracentrifuge by schlieren optics. The diffusion behavior can be understood in terms of the nonideality of the proteoglycan. The magnitude of the nonideality is dominated by charge interactions, whereas the influence of molecular size and associated excluded‐volume interactions is small. The concentration dependence of the apparent diffusion coefficient of the proteoglycan subunit from dynamic light scattering was found, in contrast, to decrease with increasing concentration. Computer simulation of the dynamic light scattering suggests that the presence of a small population of aggregates may account for the difference in the two types of diffusion measurement due to their marked influence on the scattering.
Enthalpies of transfer for proteins from aqueous to water‐alcohol solutions: A test for models of residues exposed to solvent
Authors: Schrier M. Y. , Defoster G. , Schrier E. E. , Starzak M.
Published: May 2005

The enthalpies of transfer of proteins from aqueous solution to alcohol–water solutions are used as probes of solvent‐accessible surface for these proteins. Enthalpies of transfer to 10 wt% ethanol solutions are determined calorimetrically for the native proteins ribonuclease A, lysozyme, and ovalbumin. Ribonuclease A and lysozyme are reduced and carboxamidomethylated to produce configurations in which interior residues of the native protein are exposed to the solvent; enthalpies of transfer are determined for these species. These data are then compared with enthalpies of transfer for the constituent amino acids of the proteins. The enthalpies of transfer for the residues are used to generate a maximal enthalpy of transfer that can be compared with the enthalpies of transfer for the reduced, carboxamidomethylated proteins. The residue amino acid enthalpies are coupled with probabilities that each residue is an exterior residue to predict an enthalpy of transfer for the native protein that can be compared with the observed enthalpy. The probabilities developed by Wertz and Scheraga and Lee and Richards, and Chothia are then compared on their ability to predict the native enthalpies of transfer for the protein. The Wertz–Scheraga model gives the better fit of this data in all cases.
Crowned dopa's, their dimers, cyclodimers and polymers: Synthesis and cation complexation
Authors: Berthet Michele , Sonveaux Etienne
Published: May 2005

Optically pure protected L‐[3,4‐(1,4,7,10,13‐pentaoxatridecamethylene) phenyl] alanine, its dipeptide, diketopiperazine and homopolymer, protected L‐[3,4‐(1,4,7,10,13,16‐hexaoxahexadecamethylene) phenyl] alanine and its polymer have been synthesized and characterized. These crown ether derivatives complex the potassium and ammonium cations as well as protonated leucine and glycine in tetrahydrofuran and methanol. They are also phase‐transfer agents. The cooperativity of the crown units was studied in detail for the dimeric ligands.
Determination of thermodynamic functions from scanning calorimetry data
Authors: Kidokoro Shun‐Ichi , Wada Akiyoshi
Published: May 2005

We present a theoretical basis and new methods for the determination of thermodynamic functions from scanning calorimetry data. A thermodynamic state is defined here as an ensemble of microstates in the system, and it can be defined only through assumptions of its heat capacity function and the two integral constants. With these assumptions, scanning calorimetry data can be analyzed using the single or double (or multi‐) deconvolution presented here. New equations to calculate the van't Hoff enthalpy function and the calorimetric enthalpy function are presented. We prove that the agreement of these two functions is a necessary and sufficient factor for the condition that the system can be described with the assumed two‐state model.
Loop formation in polynucleotide chains. II. Flexibility of the anticodon loop of tRNAPhe
Authors: Marky Nancy L. , Olson Wilma K.
Published: May 2005

The flexibility of hairpin loops containing n bases (residues) has been examined using a theoretical model [N. L. Marky and W. K. Olson (1982), Biopolymers, 21, 2329–2344] of oligonucleotide loop closure. The study is based on correlated probabilities of chain separation and terminal residue orientation as outlined previously. The probabilities are calculated using standard statistical mechanical methods as functions of local conformational changes of the chain backbone. Our results for an RNA chain of 9 residues suggest that the anticodon loop is a dynamic structure capable of assuming a variety of different spatial conformations. Free energy values related to the various conformations span a narrow range of values (2–4 kcal/mole) and compare well with experimental observations in aqueous solution. Conformational transitions between the loop conformations are within less than 0.5 kcal/mole in free energy. The different spatial loop conformations and the likely pathways between them may have potential relevance to the molecular translation of the genetic code.
The optical properties of Li‐ and Na‐DNA films
Authors: Weidlich T. , Lindsay S. M. , Rupprecht A.
Published: May 2005

We have measured the refractive indices of highly crystalline Li‐ and Na‐DNA wet‐spun films as a function of their water content using an immersion technique. We calculated the molecular polarizabilities of a DNA base pair using the Lorentz–Lorenz relation for anisotropic materials, the measured water contents, and densities corrected for void formation. For Li‐DNA, the polarizabilities are independent of the relative humidity, whereas for Na‐DNA, there are large changes at the A‐B transition and also at low humidities. The average polarizability of A‐Na‐DNA is in agreement with that calculated from refractive index increments and also as calculated by a simple addition of bond polarizabilities, whereas the values for Li‐ and B‐Na‐DNA are about 30% larger than the calculated values. We propose that these anomalous values are due to nonlinear polarizabilities of the phosphate group.
Conformation of the oligonucleotide d(AAAAAATTTTTT)2 by two‐dimensional nuclear overhauser effect spectroscopy and its relevance to poly(dA) · poly(dT)
Authors: Roy Siddhartha , Borah Babul , Zon Gerald , Cohen Jack S.
Published: May 2005

Conformational analysis from the pattern and intensities of cross‐peaks in the two‐dimensional nuclear Overhauser effect proton nmr spectra of the homopolymer, poly(dA) · poly(dT), and the analogous oligomer, d(AAAAAATTTTTT)2, indicate that they both exist in the B‐conformation. The conformation of the ApT/TpA junction in the oligomer is significantly different from the rest of the base pairs.
A proton NMR spin‐lattice relaxation study of the imino proton exchange kinetics in calf‐thymus DNA
Authors: Bendel Peter
Published: May 2005

The results of semiselective 1H‐nmr inversion recovery experiments on sonicated calf thymus DNA fragments are reported. The measurements were conducted in aqueous solutions containing 85% D2O, in order to reduce the dipolar contribution to the observed relaxation rates. In solutions containing 0.2M NaCl, 0.4 mM EDTA, and 10 mM cacodylate at pH = 7.0, the exchange rates of the imino protons in A‐T base pairs confirm values published earlier in the literature, extrapolating to 0.25 s−1 at 25°C. Corresponding values for the G‐C base pairs are published for the first time, and are about sixfold slower. The addition of up to 0.1M Tris buffer (pH = 7.3 at 25°C), caused a striking increase in the measured exchange rates for both the A‐T and G‐C imino protons, resembling the effect recently observed for poly(rA)‐poly(rU) and poly(rI)‐poly(rC), and suggesting that the exchange rates measured for nucleic acid duplexes in low buffer concentrations at neutral pH do not reflect base‐pair opening rates as assumed in the past. Lower limits to the base‐pair opening rates could be estimated from extrapolation of the experimental data to infinite buffer concentration, and are 1 × 103 s−1 for the A‐T, and 50 s−1 for the G‐C, base paris at 62°C.
The hydrogen bonding of cytosine with guanine: Calorimetric and 1H‐NMR analysis of the molecular interactions of nucleic acid bases
Authors: Williams Loren Dean , Chawla B. , Shaw Barbara Ramsay
Published: May 2005

The enthalpy of hydrogen‐bond formation between guanine (G) and cytosine (C) in o‐dichlorobenzene and in chloroform at 25°C has been determined by direct calorimetric measurement. We derivatized 2′‐deoxyguanosine and 2′‐deoxycytidine at the 5′‐ and 3′‐hydroxyls with triisopropylsilyl groups; these groups increase the solubility of the nucleic acid bases in nonaqueous solvents. Such derivatization also prevents the ribose hydroxyls from forming hydrogen bonds. Consequently, hydrogen‐bond formation in our system is primarily between the bases, and to a lesser extent, between base and solvent, and can be measured directly with calorimetry. To obtain the data on base‐pair formation, we first took into account the contributions from self‐association of each base, and where possible, have determined the ΔH of self‐association. From isoperibolic titration calorimetry, our measured ΔH of C2 formation in chloroform is −1.7 kcal/mol of C. Our measured ΔH of C:G base‐pair formation in o‐dichlorobenzene is −6.65 ± 0.32 kcal/mol. Since o‐dichlorobenzene does not form hydrogen bonds, the ΔH of C:G base‐pair formation in this solvent represents the ΔH of the hydrogen‐bonding interaction of C with G in a nonassociating solvent. In contrast, our measured ΔH of C:G base‐pair formation in chloroform is −5.77 ± 0.20 kcal/mol; thus, the absolute value of the enthalpy of hydrogen bonding in the C:G base pair is greater in o‐dichlorobenzene than in chloroform. Since chloroform is a solvent known to form hydrogen bonds, the decrease in enthalpic contribution to C:G base pairing in chloroform is due to the formation of hydrogen bonds between the bases and the solvent. The ΔH of hydrogen bonding of G with C reported here differs from previous indirect estimates: Our measurements indicate the ΔH is 50% less in magnitude than the ΔH based on spectroscopic measurements of the extent of interaction. We have also observed that the enthalpy of hydrogen bonding of C with G in chloroform is greater when G is in excess than when C is in excess. This increased heat is due to the formation of C:Gn > 1 complexes that we have observed using 1H‐nmr. Although C:G2 structures have previously been observed in triple‐stranded polymeric nucleic acids, higher order structures have not been observed between C and G monomers in nonaqueous solvents until now. By using monomers as a model system to investigate hydrogen‐bonding interactions in DNA and RNA, we have obtained the following results: A direct measurement of the ΔH of hydrogen bonding in the C:G complex in two nonaqueous solvents, and the first observation of C:Gn > 1 complexes between monomers. These results reinforce the importance of hydrogen bonding in the stabilization of various nucleic acid secondary and tertiary structures.