bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthetic probes for the α‐factor receptor
Authors: Naider Fred , Yaron Arieh , Ewenson Ariel , Tallon Michael , Xue Chu‐Biao , Srinivasan Jaya V. , Eriotou‐Bargiota Effimia , Becker Jeffrey M. 
Published: December 2004

AbstractThe binding of the tridecapeptide yeast mating phermone, α‐factor, to its receptor represents an excellent model for the investigation of peptide hormone–receptor interactions. In this paper we present a number of strategies to probe the binding site of the α‐factor receptor, and discuss the synthesis of probes containing radioactive and affinity tags. Preferential acylation of the α‐ or ε‐amine in [Nle12]‐α‐factor was accomplished using 3‐[3,5‐diiodo‐4‐hydroxyphenyl] propanoic acid hydroxysuccinimide ester (diiodo Bolton‐Hunter reagent). At pH 8.0 in a N‐N‐dimethylformamide/water mixture the ratio of ε‐ to α‐acylation was 2.15 to 1, whereas at pH 6.5 in a 1,2‐dimethyoxyethane/water mixture α‐acylation was favored by more than 3 to 1. The product distribution was sound to depend on pH, organic cosolvent, and the ratio of organic solvent and aqueous buffer. Product distributions were followed using analytical high performance liquid chromatography and the products were characterized enzymatically and by mass spectrometry. Citraconic anhydride preferentially α‐acylated [Nle12]‐α‐factor and served as a temporary masking group during the synthesis of ε‐Bolton–Hunter acylated phermone. Biotin or diiodo Bolton–Hunter reagents were also directly incorporated into [Nle12]‐α‐factor or Lys[Nle12]‐α‐factor during peptide synthesis. The peptides were assembled on a chloromethyl polystyrene resin or on a (phenylace‐tamido)methyl resin, and cleaved using anhydrous hydrogen fluoride (HF). Probes were inserted on amino groups either prior (biotin) or subsequent (Bolton–Hunter reagent) to HF cleavage. The biological activity of the synthetic peptides was characterized using growth arrest assays. These studies provide insights into the structural requirements for binding of α‐factor to its receptor and form a basis for detailed investigation of the receptor using biochemical procedures.
The vacuum UV CD bands of repeating DNA sequences are dependent on sequence and conformation
Authors: Gray Donald M. , Johnson Kenneth H. , Vaughan Marilyn R. , Morris Patricia A. , Sutherland John C. , Ratliff Robert L. 
Published: December 2004

AbstractCD spectra were obtained for eight synthetic double‐stranded DNA polymers down to at least 175 nm in the vacuum uv. Three sets of sequence isomers were studied: (a) poly[d(A‐C) · d(G‐T)] and poly[d(A‐G) · d(C‐T)], (b) poly[d(A‐C‐C) · d(G‐G‐T)] and poly[d(A‐C‐G) · d(C‐G‐T)], and (c) poly[d(A) · d(T)], poly[d(A‐T) · d(A‐T)], poly[d(A‐A‐T) · d(A‐T‐T)], and poly[d(A‐A‐T‐T) · d(A‐A‐T‐T)]. There were significant differences in the CD spectra at short wavelengths among each set of sequence isomers. The (G · C)‐containing sequences had the largest vacuum uv bands, which were positive and in the wavelength range of 180–191 nm. There were no large negative bands at longer wavelengths, consistent with the polymers all being in right‐handed conformations. Among the set of sequences containing only A · T base pairs, poly[d(A) · d(T)] had the largest vacuum uv CD band, which was at 190 nm. This CD band was not present in the spectra of the other (A · T)‐rich polymers and was absent from two first‐neighbor estimations of the poly[d(A) · d(T)] spectrum obtained from the other three sequences. We concluded that the sequence dependence of the vacuum uv spectra of the (A · T)‐rich polymers was due in part of the fact that poly[d(A) · d(T)] exists in a noncanonical B conformation.
Synthesis, crystal structure, and molecular conformation of peptide N‐Boc‐L‐Pro‐dehydro‐Phe‐L‐Gly‐OH
Authors: Patel H. C. , Singh T. P. , Chauhan V. S. , Kaur P. 
Published: December 2004

AbstractThe peptide N‐Boc‐L‐Pro‐dehydro‐Phe‐L‐Gly‐OH was synthesized by the usual workup procedure and finally coupling the N‐Boc‐L‐Pro‐dehydro‐Phe to glycine. The peptide crystallizes in monoclinic space group P21 with a = 8.951(4) Å, b = 5.677 (6) Å, c = 21.192(11) Å, β = 96.97(4)°, V = 1069(1) Å3, Z = 2, dm = 1.295(5) Mgm−3, and dc = 1.297(4) Mgm−3. The structure was determined by direct methods using SHELXS86. The structure was refined by the block‐diagonal least‐squares procedure to an R value of 0.074 for 1002 observed reflections. The C–C distance of 1.33(2) Å is an appropriate double bond length. The angle C–C–C is 133(1)°. The peptide backbone torsion angles are θ1 = −167(1)°, ω0 = 179(1)°, ϕ1 = −48(1)°, ψ1 = 137(1)°, ω1 = 175(1)°, ϕ2 = 65(2)°, ψ2 = 15(2)°, ω2 = −179(1)°, and ϕ3 = −166(1)°. These values show that the Boc group has a trans–trans conformation while the peptide backbone adopts a β‐turn II conformation, which is stablized by an intramolecular hydrogen bond of length of 3.05(1) Å. The structures of dehydro‐Phe containing peptides suggest that the dehydro‐Phe promotes the β‐turn II conformation. The five‐membered pyrrolidine ring of the Pro residue adopts an ideal Cγ‐exo conformation with torsion angles χ = −24(1)°, χ = 34(1)°, χ = −30(1)°, χ = 15(1)°, and θ = 6(1)°. The side chain torsion angles in dehydro‐Phe are χ = −1(2)°, χ = −176(1)°, and χ = 8(2)°. The Plane of C–C–C is rotated with respect to the plane of the phenyl ring at 7(1)°, which indicates that the atoms of the side chain of dehydro‐Phe are essentially coplanar. The molecules form a 21 screw axis related hydrogen‐bonded rows along the b axis.
Kinetics of cooperative ligand–lattice binding: Fast Monte Carlo integration
Authors: Reiter Johannes , Epstein Irving R. 
Published: December 2004

AbstractA fast Monte Carlo integration algorithm with varying time step is described for cooperative binding of ligands of arbitrary length to a one‐dimensional lattice. This algorithm is particularly suitable for strongly cooperative or anticooperative systems, i.e., when the time scales for different kinetic events are very different. As an application, the kinetics of a bimodal two‐ligand system are briefly discussed.
The binding of substituted cis‐Pt(II)‐diammines to duplex DNA
Authors: McCarthy Sharon L. , Hinde Robert J. , Miller Kenneth J. , Anderson Janet S. , Basch Harold , Krauss Morris 
Published: December 2004

AbstractThe results of a study of the binding to DNA of substituted cis‐Pt(II) diammines, (cis‐DP) are presented. Computer modeling of a series of cis‐Pt(NH2R)—where R = H, CH3, cyclopropyl, cyclobutyl, and cyclopentyl—to N7(G) atoms of two adjacent intrastrand guanine bases in a square planar complex in a pentamer duplex of DNA were performed. The stability of the complexes is studied by calculating the relative conformational energy of the cis‐DP–DNA complexes with molecular mechanics (MM) and the intrinsic binding energy, which is the relative binding energy for ligand replacement in the presence of the substituents R with quantum mechanics. In the model, the receptor site geometry and the conformation of the DNA is changed little in the accommodation of the series of monosubstituted diammines. These diammines bind to one family of DNA conformations, denoted as IC in a previous study, and this suggests that a common conformational feature in the DNA may exist to explain the smooth trend in activity. The slight increase in van der Waals energy resulting from an increasing number of atoms in the substituents is countered by a larger decrease in the ligand replacement energy as the substituent increases in size. This overall decrease in relative energy is consistent with the slight decrease in activity as the substituent size increases.
1H‐Nmr stereospecific assignments by conformational data‐base searches
Authors: Nilges Michael , Clore G. Marius , Gronenborn Angela M. 
Published: December 2004

AbstractA search procedure is described for making stereospecific assignments at prochiral centers in proteins on the basis of nuclear Overhauser enhancement and coupling constant data derived from nmr experiments. A data base comprising torsion angles, associated 1H‐1H coupling constants and interproton distances is searched by a computer algorithm for sets of values that match the experimental data within specified error limits. Two different data bases are used. The first is a crystallographic data base derived from 34 well‐refined crystal structures; the second is a systematic data base derived from conformations of a short peptide fragment with idealized geometry by systematically varying the ϕ,ψ, and χ1 torsion angles. Both approaches are tested for β‐methylene groups with model data obtained from 20 crystal structures. The results for the two methods are similar though not identical, so that a combination of the two methods appears to be useful. With an appropriate choice of error estimates, around 80% of the β‐methylene groups could be assigned in the test calculations. In addition, results with experimental nmr data indicate that a similar percentage of stereospecific assignments can be made in practical situations.
A conformational comparision of two stereoisomeric cyclic dermorphin analogues employing nmr and computer simulations
Authors: Mierke Dale F. , Schiller Peter W. , Goodman Murray 
Published: December 2004

AbstractIn a continuation of our program to study the structure–activity relationship of peptide opiates, we report the conformational analysis of two cyclic tetrapeptides related to dermorphin—Tyr‐c[D‐Orn‐Phe‐Asp]‐NH2 and Tyr‐c[D‐Asp‐Phe‐Orn]‐NH2. These analogues have similar binding properties marked by a high selectivity for the μ‐opioid receptors because of a drastic decrease in the affinity for the δ‐opioid receptor. The conformational preferences of these analogues of dermorphin determined from proton nmr, molecular dynamics, and energy minimizations are quite similar. The constraint of the 13‐membered ring formed from cyclization is quite evident from the conformational analysis. The constrained ring system acts as a template maintaining the relative orientation of the exocyclic tyrosine and side chain of phenylalanine. Two intramolecular hydrogen bonds measured for the D‐Orn analogue in DMSO were disrupted upon the addition of water. For the D‐Asp analogue, two intramolecular hydrogen bonds were found stable in DMSO and water. The global conformations of the two peptides determined from nuclear Overhauser effects did not change with the solvent titration. The difference in the hydrogen bonding within the 13‐membered ring may account for the slight differences observed in the efficacy of the analogues at the μ‐opioid receptors.
Determination of solution conformation of DNA backbone: Application of homonuclear (J, δ) spectroscopy
Authors: Hosur R. V. , Chary K. V. R. , Saran Anil , Govil Girjesh , Miles H. Todd 
Published: December 2004

AbstractHomonuclear two‐dimensional (J,δ) proton spectroscopy has been suggested as a method for the measurement of 1H‐31P coupling constants in oligonucleotides. The technique has been applied to a dinucleoside monophosphate G2′p5′C and a deoxydecanucleotide d(ACATCGATGT). PCILO energy calculations have been carried out to find minimum energy conformations with respect to the DNA backbone torsion angle ε, and these have been considered for the interpretation of the observed H3′‐31P coupling constants in oligonucleotides.
Disaccharide conformational flexibility. II. Molecular dynamics simulations of sucrose
Authors: Tran V. H. , Brady J. W. 
Published: December 2004

AbstractMolecular dynamics simulations have been used to study the motions in vacuum of the disaccharide sucrose. Ensembles of trajectories were calculated for each of the five local minimum energy conformations identified in the adiabatic conformational energy mapping of this molecule. The model sucrose molecules were found to exhibit a variety of motions, although the global minimum energy conformation was found to be dynamically stable, and no transitions away from this structure were observed to occur spontaneously. In all but one of these vacuum trajectories, the intramolecular hydrogen bond between residues was maintained, in accord with recent nmr studies of this molecule in aqueous solution. Considerable flexibility of the furanoid ring was found in the trajectories. No “flips” to the opposite puckering for this ring were found in the simulations starting from the global minimum, although such a transition was observed for a trajectory initiated with one of the higher local minimum energy conformations. Overall, the observed structural fluctuations were consistent with the experimental picture of sucrose as a relatively rigid molecule.
The interaction of cyclosporin and calmodulin
Authors: Steiner Robert F. , Albaugh Sharon 
Published: December 2004

AbstractThe interaction of cyclosporin A and dansyl cyclosporin A with bovine and wheat germ calmodulin has been monitored by measurements of induced changes in dansyl and bound toluidinyl naphthalene sulfonate fluorescence. The interaction is Ca2+‐dependent and 1 : 1 Measurements of the efficiency of radiationless energy transfer from bound dansyl cyclosporin A to an acceptor group located on Cys‐27 of wheat germ calmodulin suggest that the primary binding site is not located on the N‐terminal lobe (residues 1–65). However, studies with proteolytic fragments of calmodulin indicate that elements of the N‐terminal half‐molecule (residues 1–77) may be involved in the stabilization of the binding site. The binding of cyclosporin alters the physical properties of calmodulin and, in particular, reduces the localized rotational mobility of a fluorescent probe.
X‐ray diffraction studies on the cross‐β form of poly (O‐benzyl‐L‐serine)
Authors: Takeda Yasuhiro 
Published: December 2004

AbstractPoly(O‐benzyl‐L‐serine) of degree. polymerization 90 in oriented film cast from dichloroacetic acid (DCA) solution yielded the x‐ray patterns of the intramolecular cross‐β form, in which the extended segments stand upward and downward to the surfaces of a thin film. These x‐ray photographs further suggest that residual solvent molecules are bound to the polymer, and it may provide an important clue in understanding the nature of the cross‐β conformation in a diluted DCA solution.
Contribution of asymmetric ligand binding to the apparent permanent dipole moment of DNA
Authors: Plum G. Eric , Bloomfield Victor A. 
Published: December 2004

AbstractDespite its antiparallel symmetry, DNA often appears to possess a permanent electric dipole moment in transient electro‐optical experiments. We propose that this may be due to the asymmetric binding of charged ligands to the DNA. We have used the fluctuating dipole theory of Kirkwood and Shumaker to calculate the contribution of asymmetric ligand binding to the electro‐optic orientation function, and Monte Carlo computer simulation to calculate the reversing pulse behavior, as a function of ligand binding density. The results indicate that the effect should be observable even against the background of the sizable induced dipole moment produced by polarization of the counterion atmosphere.
The effects of hydration on the dynamic mechanical properties of elastin
Authors: Lillie M. A. , Gosline J. M. 
Published: December 2004

AbstractThe dynamic mechanical properties of elastin have been quantified over a temperature and hydration range appropriate for a biological polymer. Composite curves of the tensile properties at constant water contents between 28.1 and 44.6% (g water/100 g protein) were typical of an amorphous polymer going through its glass transition. Water content had no effect on the shape of the curves, but shifted them a distance aC along the frequency axis. The combined effects of hydration and temperature are given in a series of isoshift curves where elastin's properties are constant along any one curve. A 1% change in hydration has the same effect as a 1°–2° change in temperature, depending on the initial water content and temperature. Theoretical isoshift curves that matched the experimental data were predicted using the WLF equation and coefficients determined from the data. These data form a basis to predict the role of elastin in arterial disease based on changes in its chemical and physical environment.
Theory for the extension of a linear polyelectrolyte attached at one end in an electric field
Authors: Schurr J. Michael , Smith Steven B. 
Published: December 2004

AbstractA simple theory is developed for the extension of a uniformly charged linear polyion attached at one end in an electric field. For a polyion consisting of a very large number (N) of Kuhn lengths (b), the mean extension in the direction of the electric field (E) is given accurately by Rz = (b/A) In (sinh (NA)/NA), where A = EQb/kBT and Q is the effective charge associated with each Kuhn length. For any value of E, no matter how small, a polyion of sufficient length, such that NA ≫ 1.0, will be essentially fully extended. When A ≪ 1.0, as is the case for DNA in weak electric fields, the head end of the chain is only weakly oriented, even though the stem and tail may be completely aligned. In the linear regime, NA < 1.0, Rz is proportional to E, Q, and N2. The linear density of chain elements is calculated for a chain in the linear regime. This theory provides a basis to determine the product Qb from direct microscopic measurements of Rz vs. E for fluorescent‐labeled circular DNAs that are topologically snared near voids or surfaces of gels. Experimental realization of this suggestion is described in the following paper.
Langevin modes of macromolecules: Applications to crambin and DNA hexamers
Authors: Kottalam J. , Case D. A. 
Published: December 2004

AbstractLangevin modes described the behavior of atoms moving on a harmonic potential surface subject to viscous damping described by a classical Langevin equation. We present applications to the protein crambin and to the DNA duplex d(CpGpCpGpCpG)2 and its complex with ethidium. Our friction matrix is weighted according to surface area exposed to solvent, and results are reported for various values of the solvent viscosity and models for hydro‐dynamic interactions. Even for relatively small solvent friction (η = 0.3 cp) a substantial number of modes are overdamped, and time correlation functions decay smoothly without the oscillations characteristic of gas‐phase calculations. Perturbation theory starting from the gas‐phase modes is accurate for many low‐frequency modes (which are overdamped in the presence of solvent), but fails badly for higher modes. For correlation functions of interest to fluorescence depolarization or nmr relaxation, the plateau values are insensitive to solvent viscosity, but the relaxation times are not. The advantages and limitations of this analysis of macromolecular motions are discussed.
Cooperativity of carbohydrate moiety orientation and β‐ turn stability is determined by intramolecular hydrogen bonds in protected glycopeptide models
Authors: Hollosi M. , Perczel A. , Fasman G. D. 
Published: December 2004

AbstractThe 2, 3, 4, 6‐Tetra‐O‐acetyl‐β‐D‐gluco‐, and β‐D‐galactopyranosides, as well as approximately 4 : 1 anomeric mixtures of α‐ and β‐mannopyranosides of Boc‐X‐Y‐NHCH3 dipeptides (X‐Y = Pro‐Ser, Pro‐D‐Ser, Val‐Ser, Val‐D‐Ser, and Gly‐Ser) have been synthesized. CD and ir spectroscopic studies were performed to characterize the conformation of the glycosylated peptide backbone and examine the possible formation of intrapeptide and glycopeptide intramolecular H‐bonds. It was found that O‐glycosylated peptides containing a D‐serine residue are likely to adopt a type II β‐turn while those with the Pro‐Ser or Val‐Ser sequence feature a type I(III) β‐turn in solution. Glycosylation also increases the magnitude of the CD bands, characteristic of the given type of β‐turns, which can be interpreted as an indication of the stablization of the folded backbone conformation. Infrared data showed that in nonpolar solutions the peracetyl glycopeptides adopt both single‐ and double H‐bonded conformations whose ratio, in some cases, depends on the position at C‐2′ of the H‐bond acceptor acetoxy group. These data suggest that five‐, seven‐, or ten‐membered glyco‐turns may play an important role in fixing the steric orientation of the carbohydrate antennae systems in glycoproteins.
A molecular dynamics investigation of the elastomeric restoring force in elastin
Authors: Wasserman Z. R. , Salemme F. R. 
Published: December 2004

AbstractA repetitive polypentapeptide organized as a connected chain of β‐bends is believed to be an important structural element of elastin, the major elastomer in biological systems. Molecular dynamics simulations were carried out on hydrated polymers of (Val‐Pro‐Gly‐Val‐Gly)18 at various extensions. Analysis of the fluctuations of backbone angles in relaxed elastin showed that particularly large‐amplitude torsional motions occur in ϕ and ψ angles of residues connecting sequentially adjacent hairpin bends. Many such motions reflect peptide plane librations that result from anticorrelated crankshaft rotations of ψi and ϕi+1. These effects were much reduced in stretched polymer models. The conformational entropy of relaxed and stretched elastin models was estimated using a treatment due to Meirovitch, and gave a calculated decrease in entropy of about 1 cal/mol deg when the polymer was stretched to 1.75 times its original length. There are large changes in solvent‐accessible surface area during the intitial stages of elastin stretching. Collectively these results suggest that hydrophobic interactions make contributions to elastin entropy at low extensions, but that librational mechanisms make large contributions to the elastic restoring force at longer extensions.
Determining minimum energy conformations of polypeptides by dynamic programming
Authors: Vajda Sandor , Delisi Charles 
Published: December 2004

AbstractA combinatorial optimization approach is used for solving the multiple‐minima problem when determining the low‐energy conformations of short polypeptides. Each residue is represented by a finite number of discrete states corresponding to single residue local minima of the energy function. These precomputed values constitute a search table and define the conformational space for discrete minimization by a generalized dynamic programming algorithm that significantly limits the number of intermediate conformations to be generated during the search. Since dynamic programming involves stagewise decisions, it results in buildup‐type procedures implemented in two different forms. The first procedure predicts a number of conformations by a completely discrete search and these are subsequently refined by local minimization. The second involves limited continuous local minimization within the combinatorial algorithm, generally restricted to two dihedral angles in a buildup step. Both procedures are tested on 17 short peptides previously studied by other global minimization methods but involving the same potential energy function. The discrete method is extremely fast, but proves to be successful only in 14 of the 17 test problems. The version with limited local minimization finds, however, conformations in all the 17 examples that are close to the ones previously presented in the literature or have lower energies. In addition, resutls are almost independent of the cutoff energy, the most important parameter governing the search. Although the limited local minimization increases the number of energy evaluations, the method still offers substantial advantages in speed.