bluuebunny/crossref_metadata_2025_split huggingface dataset:
Partial intercalation with DNA of peptides containing two aromatic amino acids
Authors: Robledo‐Luiggi Cynthia , Wilson W. David , Pares Elsie , Vera Marisol , Martinez Carmen S. , Santiago Daphne 
Published: December 2004

AbstractThe interactions with DNA of tetrapeptide amides containing lysine at the N‐terminal position and aromatic amino acids at the second and fourth positions (Ala at position three), 1–6, have been investigated by nmr, CD, and viscometric methods. Tetrapeptides with N‐terminal lysine and a single aromatic amino acid, 7–10, were investigated as controls. Significant decreases in DNA viscosity occurred on addition of 7, with the aromatic group at the second position, but not with any of the other single aromatic amino acid peptides. All of the tetrapeptides with two aromatic groups caused DNA viscosity decreases which were two to three times larger than with 7. Peptides with p‐nitrophenylalanine (p‐NO2Phe) as the aromatic group were synthesized for nmr studies because of its simpler aromatic nmr spectrum relative to Phe. Large upfield shifts of the aromatic proton signals were obtained when the amino acid in the second position was L‐p‐NO2Phe, and the fourth position contained either p‐NO2Phe or Phe. Such peptides also caused the largest DNA viscosity decreases on complex formation. Smaller upfield shifts of the aromatic signals were obtained when the amino acid in the second position was L‐Phe or a D isomer of Phe orp‐NO2Phe. With all peptides, larger upfield nmr shifts were obtained with heat‐denatured, recooled DNA than with native DNA under the same conditions. As with nmr, CD results are quite different for the peptides with L and D amino acids at the second position. All of the results can be interpreted in terms of a model in which lysine interacts stereospecifically with the backbone in a DNA double helix and the aromatic group at the second position stacks strongly with the base pairs when the amino acid is an L isomer. The aromatic group at the fourth position can also interact with the base pairs, but primarily through a sideways stacking of the aromatic group with base pairs for either L or D isomers. Because of covalent constraints on the separation distance for the two aromatic groups in the tetrapeptides. they must stack on opposite sides of the same base pair in violation of the neighbor exclusion principle observed with classical intercalators. This stacking at the same base pair no doubt accounts for the larger viscosity decreases in DNA with the peptides containing two aromatic groups relative to those with a single aromatic group. Such protein–induced conformationai changes may be very important in protein‐DNA or RNA recognition, and in opening of DNA by single‐stranded binding proteins and enzymes such as RNA polymerase.
Synthesis, crystal structure, and molecular conformation of N‐Ac‐dehydro‐Phe‐L‐Val‐L‐Val‐OCH3
Authors: Narula P. , Khandelwal B. , Singh T. P. 
Published: December 2004

AbstractThe peptide N‐Ac‐dehydro‐Phe‐L‐Val‐L‐Val‐OCH3 (C22H31N3O5) was synthesized by the usual workup procedure and finally by coupling the N‐Ac‐dehydro‐Phe‐L‐Val‐OH to valine methyl ester. It was crystallized from its solution in acetonitrile‐water mixture at 4°C. The crystals belong to the space group P1 with a = 8.900(3) Å, b = 11.135(2) Å, c = 12.918(2) Å, α = 90.36(1)°, β = 110.14(3)°, γ = 90.10(3)°, V = 1207.7(6) Å,3 Z = 2, dm = 1.156(5) Mgm−3, dc = 1.148(5) Mgm−3. The structure was determined by direct methods using SHELXS86. The structure was refined by full‐matrix least‐squares procedure to an R value of 0.077 for 3916 observed reflections. The molecular dimensions and conformations of the two crystallographically independent molecules are in good agreement. In the dehydro residues, the average Cα–Cβ distance is 1.31(2) Å whereas the bond angle Cα–Cβ–Cγ is 132(1)°. The average backbone torsion angles are ω0 = 169(1)°, ϕ1 = −40(1)°, ψ1 = −50(1)°, ω1 = −177(1)°, ϕ2 = 54(1)°, ψ2 = 46(1)°, ω2 = −174(l)°, ϕ3 = 103(1)°, ψ = −139(1)°, and θ = −176(1)°. The acetyl group is in the trans conformation, while the backbone adopts a right‐handed and left‐handed helical conformation alternatingly. The two crystallographically independent molecules are held together by three hydrogen bonds: N21–H21–O′12 = 2.911(12) Å, N22–H22–O′11 = 2.941(12) Å and N23–H23–O11 = 3.005 (9) Å. The crystal structure is stabilized by van der Waals forces and three additional hydrogen bonds: N11–H11–O2, = 2.896(15) Å, N12–H12–O′21 = 2.947(14) Å and N13–H13–O21 = 2.987(15) Å.
Mass‐weighted molecular dynamics simulation of cyclic polypeptides
Authors: Mao Boryeu , Maggiora G. M. , Chou K. C. 
Published: December 2004

AbstractA modified molecular dynamics (MD) method in which atomic masses are weighted was developed previously for studying the conformational flexibility of neuroregulating tetra‐peptide Phe‐Met‐Arg‐Phe‐amide (FMRF‐amide). The method has now been applied to longer and constrained molecules, namely a disulfide‐linked cyclic hexapeptide, c [CYFQNC], and its linear and [pseudo‐cyclic] analogues. The sampling of dihedral conformational space of the linear hexapeptide in mass‐weighted MD simulations was found to be improved significantly over conventional MD simulations, as in the case of the shorter FMRF‐amide molecule studied previously. In the cyclic hexapeptide, the internal constraint of the molecule due to the intramolecular disulfide bond (hence the absence of free terminals in the molecule) does not adversely affect the significant improvement of conformational sampling in mass‐weighted MD simulations over normal MD simulations. The pseudo‐cyclic polypeptide is identical to the linear CYFQNC molecule in amino acid sequence (i.e., side chains of the cysteine residues are reduced), but the positions of its two terminal heavy atoms were held fixed in space such that the molecule has a nearly cyclic conformation. For this molecule, the mass‐weighted MD simulation generated a wide range of polypeptide backbone conformations covering the internal dihedral degrees of freedom; moreover, the physical space of the pseudo‐cyclic structure was also sampled in a complete revolution of the entire molecular fragment about the two fixed termini during the simulation. These characteristics suggest that mass‐weighted MD can also be an extremely useful method for conformational analyses of constrained molecules and, in particular, for modeling loops on protein surfaces.
Drug–DNA interactions: Spectroscopic and footprinting studies of site and sequence specificity of elliptinium
Authors: Mauffret Oliver , Rene Brigitte , Convert Odile , Monnot Monique , Lescot Elie , Fermandjian Serge 
Published: December 2004

AbstractThe binding of the antitumoral ellipticine derivative 2‐methyl‐9‐hydroxyellipticinium acetate (elliptinium; NMHE) to DNA was analyzed by the combined use of DNase I foot‐printing and spectroscopic methods. Using two fragments of pBR322 DNA, five discrete NMHE binding sites of 5–7 protected base pairs (bp) were detected by footprinting at 4°C on the analyzed regions. These corresponded to alternating pyrimidines and purines. The inactive derivative 2‐methyl ellipticinium acetate L(NME) lacking a hydroxy group failed to demonstrate DNA protection even at low temperature. Ultraviolet‐absorption and 1H‐nmr analysis was performed using two autocomplementary octanucleotides d(TGACGTCA) (I) and d(ACTGCAGT) (II). The uv‐absorption titrations resulted in an intercalative binding mode for NMHE in the oligomers. Analysis of the derived biphasic Scatchard plots yielded two binding sites corresponding to ∼6‐bp and 2‐bp sizes and characterized by apparent association constants K1 ∼ 108M−1 and K2 ∼ 106M−1, respectively. The 1H‐nmr analysis of exchangeable (imino) protons and nonexchangeable protons performed in the one‐ and two‐dimensional modes confirmed the intercalation of NMHE, and further revealed the existence of multiple sites on DNA. Assuming that imino resonance line width concerned the sole kinetic effects, 10‐ms order lifetimes were estimated for the drug–oligonucleotide complexes at 7°C, pH 7, and 0.1 ionic strength. Finally examination of every drug–DNA spectra in the light of the footprinting results indicated that there was a preference for binding of NMHE to the CpG (octamer I) and TpG (octamers I and II) steps.
Anti‐insulin antibody structure and conformation. I. Molecular modeling and mechanics of an insulin antibody
Authors: Nell Laura J. , McCammon J. Andrew , Subramaniam Shankar 
Published: December 2004

AbstractA knowledge‐based three‐dimensional model of an anti‐insulin antibody, 125, was constructed using the structures of conserved residues found in other known crystallographic immunoglobulins. Molecular modeling and mechanics were done with the 125 amino acid sequences using QUANTA and CHARMm on a Silicon Graphics 4D70GT workstation. A minimal model was made by scaffolding using crystallography coordinates of the antibody HyHEL‐5, because it had the highest amino acid sequence homology with 125 (84% light chain, 65% heavy chain). The three hypervariable loop turns that are longer in 125 than in HyHEL‐5 (L1, L3, and H3) were modeled separately and incorporated into the HyHEL‐5 structure; then other amino acid substitutions were made and torsions optimized. The 125 model maintains all the structural attributes of an antibody and the structures conserved in known antibodies. Although there are many polar amino acids (especially serines) in this site, the overall van der Waals surface shape is determined by positions of aromatic side chains. Based on this model, it is suggested that hydrogen bonding may be key in the interaction between the human insulin A chain loop antigenic epitope and 125.
Conformational analysis of a dinucleotide photodimer with the aid of the genetic algorithm
Authors: Blommers Marcel J. J. , Lucasius Carlos B. , Kateman Gerrit , Kaptein Robert 
Published: December 2004

AbstractThe solution structure of the photodimer cis, syn‐dUp [ ]dT is derived with the aid of the genetic algorithm. The conformational space available for the molecule is sampled efficiently using the computer program DENISE and tested against a set of constraints available from nmr experiments. The dominant conformation in solution found with this approach can be described by the following combinations of sugar‐phosphate backbone torsion angles: ε (t), ζ(t), α(+), β(–ac), and γ(t). The conformation of the sugars and glycosidic torsion angles are S type and syn, respectively. The cyclobutane ring and pyrimidines are puckered. In addition, other conformations that exist in equilibrium with the first are found. It is concluded that the cyclobutane‐pyrimidine system is rigid, whereas the sugar‐phosphate backbone is flexible. The solution structures are compared with the crystal structure of the strongly related cyano‐ethyl ester of cis, syn‐dTp [ ]dT.
Conformation and charge distribution of bicyclic β‐lactams: Structure–activity relationships
Authors: Fernández Berta , Carballiera Luís , Ríos Miguel A. 
Published: December 2004

AbstractThe structures of 7‐oxo‐1‐azabicyclo[3.2.0] heptane and its 4‐oxa, 3‐ethylene‐4‐oxa, and 3‐ethylene‐6‐methyl‐4‐oxa derivatives, and of 8‐oxo‐1‐azabicyclo[4.2.0] octane and its 5‐oxa derivative, were studied by ab initio methods. Conformations were refined without constraints using the 4‐21G and the 4‐21G* basis sets, and energies and charge distributions were improved by single‐point 6‐31G*/4‐21G* calculations. The results are interpreted in terms of structural trends related to β‐lactamase inhibitor capability.
Helix‐forming tendencies of amino acids depend on the restrictions of side‐chain rotamer conformations: Crystal structure of the tripeptide GAI in two crystalline forms
Authors: Go Kuantee , Chaturvedi Sanjeev , Parthasarathy R. 
Published: December 2004

AbstractIn our attempts to design crystalline α‐helical peptides, we synthesized and crystallized GAI (C11H21N3O4) in two crystal forms, GAI1 and GAI2. Form 1 (GAI1) Gly‐L‐Ala‐L‐Ile (C11H21N3O4 · 3H2O) crystals are monoclinic, space group P21 with a = 8.171(2), b = 6.072(4), c = 16.443(4) Å, β = 101.24(2)°, V = 800 Å3, Dc = 1.300 g cm‐3 and Z = 2, R = 0.081 for 482 reflections. Form 2 (GAI2) Gly‐L‐Ala‐L‐Ile (C11H21N3O4 · ½H2O) is triclinic, space group P1 with a = 5.830 (1), b = 8.832 (2), c = 15.008(2) Å, α = 102.88 (1), β = 101.16(2), γ = 70.72(2)°, V = 705 Å3, Z = 2, Dc = 1.264 g cm−3, R = 0.04 for 2582 reflections. GAI1 is isomorphous with GAV and forms a helix, whereas GAI2 does not. In GAI1, the tripeptide molecule is held in a near helical conformation by a water molecule that bridges the NH+3 and COO− groups, and acts as the fourth residue needed to complete the turn by forming two hydrogen bonds. Two other water molecules form intermolecular hydrogen bonds in stabilizing the helical structure so that the end result is a column of molecules that looks like an incipient a‐helix. GAI2 imitates a cyclic peptide and traps a water molecule. The conformation angles χ11 and χ12 for the side chain are ( –63.7°, 171.1°) for the helical GAI1, and (–65.1°, 58.6°) and (–65.0°, 58.9°) for the two independent nonhelical molecules in GAI2; in GAI1, both the C, atoms point away from the helix, whereas in GAI2 the Cγ atom with the g+ conformation points inward to the helix and causes sterical interaction with atoms in the adjacent peptide plane. From these results, it is clear that the helix‐forming tendencies of amino acids correlate with the restrictions of side‐chain rotamer conformations. Both the peptide units in GAI1 are trans and show significant deviation from planarity [ω1 = –168(1)°; ω2 = –171(1)°] whereas both the peptide units in both the molecules A and B in GAI2 do not show significant deviation from planarity [ω1 = 179.3(3)°; ω2 = –179.3(3)° for molecule A and ω1 = 179.5(3)°; omega;2 = –179.4 (3) ° for molecule B], indicating that the peptide planes in these incipient α‐helical peptides are considerably bent.
β‐Alanine containing peptides: A novel molecular tool for the design of γ‐turns
Authors: Pavone V. , Lombardi A. , D'auria G. , Saviano M. , Nastri F. , Paolillo L , Di Blasio B. , Redone C. 
Published: December 2004

AbstractIn the present paper we describe the synthesis, purification, single crystal x‐ray analysis, and solution conformational characterization of the cyclic tetrapeptide cyclo‐ (L‐Pro‐γ‐Ala‐L‐Pro‐γ‐Ala). This peptide was synthesized by classical solution methods and the cyclization of the free tetrapeptide was accomplished in good yields in diluted methylene chloride solution using N, N‐dicyclohexyl‐carbodiimide (DCCI). The compound crystallizes in the orthorombic space group P212121 from ethyl acetate. All peptide bonds are trans. The molecular conformation is stabilized by two intramolecular hydrogen bonds between the CO and NH groups of the two β‐alanine residues. These hydrogen bonds take part in a C7 structure in which both proline residues occupy the 2 position of an inverse γ‐turn. The two β‐alanine residues have a typical folded conformation (around the Cα‐Cβ bond) observed in other cyclic peptides containing this residue. A detailed 1H‐nmr analysis in CD3CN solution has been carried out. The molecule assumes a twofold symmetry in solution with a molecular conformation consistent with that observed in the solid state.
The low‐temperature heat capacity of solid proteins
Authors: Edelman Jay 
Published: December 2004

AbstractSeveral harmonic models of protein fluctuations are used to calculate the heat capacity. They get the spectral density of conformational modes from inelastic neutron scattering, normal mode calculations, or macroscopic elasticity (Debye model). It is assumed that the low‐frequency spectral density depends only weakly on temperature and protein species. The Debye model predicts temperatures below which modes are primarily in their ground states: 10 and 80 K for the lattice and conformational modes, respectively. The models differ most below 100 K. The mode calculations yield the most accurate predictions, though all three models are within twofold of the data. The heat capacity has the power law form aTb for T < 30 K. The experimental b's of proteins are 1.6–1.8, and the theoretical, 1.1–1.3. One possible explanation for the discrepancy is the occurrence of transitions between discrete conformations. All of the models approach the measured data in the range 100–200 K. They are very similar above 200 K, where the heat capacity includes significant contributions from bond stretching and bending. This masks the possible anharmonic behavior of the conformational modes. Hydration substantially increases the heat capacity above 200 K. This effect seems to be a consequence of conformational transitions that have higher energy than the ones seen with low hydration. The analysis also predicts that denaturation with constant hydration produces a negligible increase of heat capacity. The larger increment in solution arises from the different hydration of the folded and unfolded states, and is responsible for the existence of cold denaturation. This phenomenon is thus predicted not to occur when the hydration is constant.
Variations in the turn‐forming characteristics of N‐Acyl proline units
Authors: Liang Gui‐Bai , Rito Christopher J. , Gellman Samuel H. 
Published: December 2004

AbstractWe have examined intramolecular hydrogen bonding in four homologous compounds, N‐acetyl‐, N‐propionyl‐, N‐i‐butyryl‐, and N‐pivaloyl‐proline‐methylamide, in methylene chloride, by means of 1H‐nmr and ir measurements. At room temperature, the major trans conformer of MeCO‐Pro‐NHMe appears to be approximately 68% intramolecularly hydrogen bonded, the trans conformers of EtCO‐Pro‐NHMe and i‐PrCO‐Pro‐NHMe are approximately 75% intramolecularly hydrogen bonded, and t‐BuCO‐Pro‐NHMe is approximately 50% intramolecularly hydrogen bonded. Thus, the internally hydrogen‐bonded state (C7 or γ‐turn) is significantly less populated for the N‐pivaloyl compound than for the other three molecules in this series. Variable temperature measurements indicate that for each proline derivative there is very little enthalpic difference between the intramolecularly hydrogen‐bonded and nonhydrogen bonded states of the trans rotamer. Changing the N‐terminal acyl group also affects intramolecular hydrogen bonding (including β‐turn formation) in end‐blocked Pro‐Gly dipeptides.
Conformational study of endothelins and sarafotoxins with the cystine‐stabilized helical motif by means of CD spectra
Authors: Tamaoki Haruhiko , Kyogoku Yoshimasa , Nakajima Kiichiro , Sakakibara Shumpei , Hayashi Mitsuo , Kobayashi Yuji 
Published: December 2004

AbstractA series of CD measurements were carried out on members of peptides in the endothelin and sarafotoxin families. The helical structures taken by these peptides containing the helical motif with the sequences of Cys‐X‐X‐X‐Cys and Cys‐X‐Cys [Y. Kobayashi et al. (1991) Neurochemistry International Vol. 18, pp. 525–534] are classified into three groups: a group of structures of ET‐1, ET‐2 and vasoactive intestinal contractor (VIC), a group of sarafotoxin, and a group of ET‐3.
Minimum energy conformations of proline‐containing helices
Authors: Polinsky Alexander , Goodman Murray , Williams Karen A. , Deber Charles M. 
Published: December 2004

AbstractProline occurs frequently in transmembrane α‐helices of transport and receptor proteins even though statistical surveys demonstrate the overwhelming preference of this residue for a non‐α‐helical, hydrophilic environment. As a result, membrane‐buried proline has been proposed to be functionally important, with function arising from structural discontinuity or destabilization of the helix. Destabilization may occur by Promediated conformational transitions between discrete states, and may be manifested in membrane protein systems through reversible processes such as channel opening and closing or signal transduction. In this study, computer modeling of a model transmembrane α‐helix, (Ala)8‐Leu‐Pro‐Phe‐(Ala)8, in a medium of low polarity (dielectric = 2), is used to examine the occurrence and energetic accessibility of Pro‐mediated conformational interconversions. Leu ψ and χ1, Pro ψ and Phe ϕ and χ1 torsion angles were assigned random values so that a data base of 200 conformations for each of the cis and trans states was generated. The conformations were minimized and low‐energy structures organized into families. This analysis demonstrated that the most populated lowest energy family is the Trans‐I conformation, corresponding to proline in a kinked α‐helix. Two additional trans structures, Trans‐II and Trans‐III, as well as a cis conformation, Cis‐I, are also energetically competitive. Interconversions between the trans states could thus be mediated by changes at a single torsion angle, accompanied by minor local hydrogen‐bonding rearrangements. This work substantiates that membrane‐buried proline can provide the basis for conformational transitions between discrete α‐helix‐based structures in a nonpolar environment.
Peptidomimetics as receptors agonists or peptidase inhibitors: A structural approach in the field of enkephalins, ANP and CCK
Authors: Roques Bernard P. 
Published: December 2004

AbstractStabilization of biologically active conformations of native peptides by cyclization or in‐troduction of hindering residues led to peptidominetics endowed with high affinity and selectivity for one class of receptors and able to cross the blood brain barrier. This is the case of BUBU, Tyr‐D‐Ser(OtBu)‐Gly‐Phe‐Leu‐Thr(OtBu) and BUBUC, Tyr‐D‐Cys‐(OtBu) ‐Gly‐Phe‐Leu‐Thr (OtBu) for the opioid δ receptors and of BC 254, Boc‐γ‐D Glu‐Tyr (SO3H)‐Nle‐D Lys‐Trp‐Nle‐Asp‐PheNH2 and of BC 264, Boc‐Tyr(SO3H) gNle‐mGly‐Trp‐MeNle‐Asp‐PheNH2 for central CCK‐B receptors. Inhibition of metabolizing peptidases such as aminopeptidase N and endopeptidase 24.11 (NEP) for enkephalins and of NEP and ACE for atrial natriuretic peptide and angiotensin I by mixed inhibitors such as kelatorphan and RB 101 or ES14, rationally designed by taking into account the structural differences in the active site of these zinc‐metallopeptidases, led to potent analgesics devoid of the major morphine side effects or to new antihypertensives.
Critical analysis of objections against the biological molecular energy machines
Authors: Křemen Alexandr 
Published: December 2004

AbstractIn the past, two important objections against McClare's idea of biological molecular energy 4 machines were raised. One of the criticisms was concerned with the origin of energy gained in ATP cleavage and with an interpretation of McClare's “excited vibrational state.” The former argument reveals a failure of the critics to comprehend McClare's approach. As to the excited vibrational state, it can be identified with nonequilibrium conformational states of the unit rather than with a single vibrational mode. The other criticism based on Brillouin's energy cost of measurement argued that reversible operation of biological molecular energy machines would be virtually impossible. Using propagation velocities of deformations of the unit's structure (instead of velocity of light), the objections against reversibility are invalidated even in the framework of the critic's approach. McClare's idea and relevant definitions are thus physically correct.
Plausible view on the biological molecular energy machines
Authors: Křemen Alexandr 
Published: December 2004

AbstractA qualitative picture of operation modes of biological molecular energy machines is presented. It is suggested that there is mutual control between the flow of molecular energy stored in a biological molecular energy machine and the sequence of nonequilibrium conformational states through which the machine passes in doing work. If the structure of the conformational space is favorable, the set of trajectories in this space decomposes into two families, each of which accomplishes another task. This divergence of trajectories enables to distinguish molecular objects according to differences in interaction between the machine and the object, i.e., to perform a measurement on a molecular object and process the object according to the result of that measurement.