摘要:

AbstractIt is noteworthy that the dehydro‐Ala residue adopts an extended conformation that is different than those observed in dehydro‐Phe, dehydro‐Leu, and dehydro‐Abu. The peptide N‐Boc‐L‐Phe‐dehydro‐Ala‐OCH3(C18H24N2O5) was synthesized by the usual workup procedure and finally by converting N‐Boc‐L‐Phe‐L‐Ser‐OCH3to N‐Boc‐L‐Phe‐dehydro‐Ala‐OCH3. It was crystallized from its solution in a methanol–water mixture at room temperature. The crystals belong to the monoclinic space group P21witha= 9.577(1) Å,b= 5.195 (3) Å,c= 19.563 (3) Å, β = 94.67 (5)°, V = 970.1(6) Å3,Z= 2, dm= 1.201(5) Mg m−3, dc= 1.197 (5) Mg m−3. The structure was determined using direct method procedures. It was refined by a full‐matrix least‐squares procedure to anRvalue of 0.048 for 1370 observed reflections. The C 2α‐C 2βdistance is 1.327 (8) Å, while the bond angles N2‐C 2α‐C 2'and C 1'‐N2‐C 2αare 109.8 (5)° and 127.8 (5)°, respectively. The backbone adopts a nonspecific conformation with dehydro‐Ala in a fully extended conformation with the following torsion angles: θl= 175.2 (4)°, ω,0= 170.2 (4)°, ø1= 135.8 (5)°, ψ1= ‐22.6(6)°, ω1= 168.5 (5)°, ψ2,= ‐170.3(5)°, ψ 2T= –178.6(5)°', θT= 178.4(7)°. The rigid planar and trans conformation of dehydro‐Ala forces Phe to adopt a strained conformation. The Boc group has atrans‐transconformation. The side‐chain torsion angles of the Phe residue are χ1= 63.3(6)°, χ 12,1= −92.1(6)°, χ12,2= 89.5 (6)°. The observed conformation is stabilized by three nonlinear intramolecular C—H‐‐‐O type of interactions. The crystal structure is stabilized by an intermolecular hydrogen bond N1—H1‐‐‐O2of distance 2.938(7) Å along thebaxis while the van der Waals forces are the stabilizing interactions in theacplane. The low‐energy conf

ISSN:0006-3525    

DOI:10.1002/bip.360321002

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractA penalty function for scalar coupling constants has been applied in molecular dynamics simulations as an experimental constraint. The function is based on the difference between the coupling constant calculated from the dihedral angle and the experimentally measured coupling constant. The method is illustrated on a model cyclic pentapeptide for which3JHN‐Hαand3JHN‐Cβ, both about the ϕ backbone dihedral angle, have been measured. The function is efficient in producing structures consistent with the scalar couplings, but removed from the conformation observed in solution. This arises from the lack ofJrestraints for the ψ dihedral angle. Simulation with both nuclear Overhauser effect (NOE) andJ‐coupling restraints illustrates small but significant differences from simulations using only NOEs. © 1992 John Wiley

ISSN:0006-3525    

DOI:10.1002/bip.360321003

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractSix cyclic peptides, designed to act as topological templates in the TASP (template assembled synthetic protein) approach in protein de novo design, were investigated employing a 100‐ps, 900‐K molecular dynamics conformational search. The peptides are composed of two Lys‐X‐Lys (X = Gly, Ala) tripeptides connected at its N‐ and C‐terminal end by a Pro‐Gly motif and a cystine bridge (I), two Pro‐Gly units (II), naphthalene derivatives (III), and tetrahydronaphthalene derivatives of different stereochemistry (IV‐VI). The molecular dynamics conformational search established that template I had β‐sheet like geometry. Templates II‐VI showed different preferential geometries, among them, e.g., distinct preferences for type V turns in Pro‐Gly containing peptides and close spatial arrangement of hydrophobic naphthalene moieties. The orientation of the lysine side chains within preferential geometries of the individual templates is analyzed and a tentative evaluation for their potential to stabilizeTASPmolecules of 4‐helix bundle topology is given.

ISSN:0006-3525    

DOI:10.1002/bip.360321004

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractThe effect of mixed salt (1:1 and 2:1 electrolyte) on alginate (a charged polysaccharide) gel formation is analyzed within the Poisson‐Boltzmann cell model utilizing experimental data from the literature. The concentration of calcium ions needed to induce gelation of alginate goes through a minimum as 1 : 1 electrolyte is added. The theoretical model can account for this in a qualitative manner. According to the theoretical model, however, it is only in terms of concentrations that the minimum exists. In terms of chemical potentials for the ions (or salt) the curve is monotonic. The effect is due to the highly nonideal interactions in polyelectrolyte solutions when the total salt content is low. © 1992 John Wiley&Sons, I

ISSN:0006-3525    

DOI:10.1002/bip.360321005

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractThe Spectroscopic properties of syringomycin E, an antibiotic lipodepsinonapeptide associated with pathological states in plants, have been investigated by uv absorbance and CD spectroscopies, and by the synthesis of relevant model compounds. Initial studies [E. Vaillo, A. Ballio, P. L. Luisi, and R. M. Thomas (1990) inPeptides 1990, Giralt, E.&Andreu, D., Eds., Escom Scientific, Leiden, Netherlands] suggested that a significant contribution to the spectra was due to the presence of azdehydroaminobutyric acid residue in the amino acid sequence. The model peptides N‐Boc‐L‐Phe‐ΔZAbu‐OMe and its analogue, N‐Boc‐L‐Phe‐L‐Thr‐OMe, lacking the unsaturated bond, were synthesized using standard solution chemistry, and a detailed investigation was made in which the spectra of the models and that of syringotoxin (an antibiotic closely related to syringomycin E but without a Phe residue) were compared with those of syringomycin E under a variety of solvent conditions. The uv absorbance spectra of both N‐Boc‐L‐Phe‐ΔZAbu‐OMe and syringomycin E clearly showed the presence of the unsaturated residue while the CD spectra were complex, environmentally sensitive, and contained contributions from both the ΔzAbu and Phe residues. In the course of these studies extinction coefficients were obtained for syringomycin E and its dipeptide model. The origins of the uv and CD spectra are discussed in detail, and a comparison is made with the spectra of other, similar lipopeptide antibiotics. Finally, a structural model for syringomycin is proposed in which the changes induced in the spectrum by alterations in the solvent environment are accommo

ISSN:0006-3525    

DOI:10.1002/bip.360321006

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractFormulations of conformational weights for helix‐coil transitions can be extended to substantially more complex situations than are usually pursued. General rules for matrix multiplication that depend parametrically on the interaction ranges and numbers of rotamers of residues are presented. The orders of the matrices of statistical weights can be increased with chain length, so that an individual matrix element can represent any specified single conformation, as needed. By the appropriate choice of interaction ranges and numbers of available conformers, approximations can be introduced in which: (1) an average of the conformations of any chain segment is obtained, (2) specific residue‐residue interactions are excluded, or (3) the conformation of a part of the chain is restricted or fixed. The method is appropriate for treating specific interactions in peptides and could be used together with available experimental information to develop models of conformational transitions. As such, the methods represent a class of calculations aimed at more rigorous calculations built around known features of a molecule. The aim is to facilitate calculations that bridge the gap between nonquantitative molecular model building and more rigorous but less directed molecular mechanics calculations. The method can directly include any desired longer range of interactions, if the interaction range is not too long to make impossible the manipulation of the requisite matrices. An outline is presented of an application to treat salt bridges in the C peptide of ribonuclease A. © 1992 John Wiley&Sons,

ISSN:0006-3525    

DOI:10.1002/bip.360321007

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractThe temperature dependencies of line shapes and spin lattice relaxation timesTlhave been measured for25Mg in dilute solutions of Na‐DNA/NaCl containing varying amounts of added magnesium(II) ions. The25Mg spectrum is clearly non‐Lorentzian, due to the presence of motions modulating the quadrupolar interaction that are slow compared to the inverse of the Larmor frequency. The weakly temperature dependent line shapes and relaxation rates appear to be influenced by the relatively slow exchange of the Mg2+ions between the DNA surface and the aqueous bulk phase. The observed temperature dependencies depend on the ratio of total magnesium to DNA phosphate, Mg/P. The line shape as well as the temperature dependence of the line width at half height can be qualitatively reproduced with a two‐site discrete exchange model for the quadrupolar relaxation of a spin\documentclass{article}\pagestyle{empty}\begin{document}$ \frac{5}{2} $\end{document}nucleus in isotropic solution. The calculations give a value of the lifetime for magnesium bound to DNA of 4 ms at room temperature. Previously reported temperature dependent43Ca relaxation measurements in DNA solution can be reproduced under the assumption of a mean lifetime of bound calcium that is not, larger than 2 ms but not smaller than 50 μs at room temperature. The temperature variation ofT1for25Mg has been calculated, giving some qualitative agreement with the data. The correlation time for bound25Mg has been found to be about 40 ns at room temperature. © 1992 John Wiley&So

ISSN:0006-3525    

DOI:10.1002/bip.360321008

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractCD spectra have been measured as a function of temperature for a number of ApA analogues with modified backbones. Oligonucleotides with these modified backbones are being used as antisense agents having potential as viral therapeutics. Results of these studies show that when a carbonyl is substituted for the phosphate to produce an uncharged backbone, the analogues that have either sugar or morpholino substitution do not stack. In contrast, when a morpholino group is substituted for the sugar and the phosphate is modified so as to be uncharged, there is strong base stacking. Stacking interactions in the phosphorus‐linked morpholino analogues are at least as strong as those found in d (ApA). The stacking interactions in ApA are weak by comparison. Singular value decomposition demonstrates that the stacking is two state, and Taylor series decomposition yields a coefficient that measures base stacking interactions. The van't Hoff equation is applied to the base stacking coefficient from the Taylor series fitting to give thermodynamic parameters. © 1992 John Wiley&Sons, I

ISSN:0006-3525    

DOI:10.1002/bip.360321009

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractThe distribution coefficients of single‐ and double‐stranded Oligodeoxynucleotides in a PEG 8000/phosphate two‐phase system are a function of their chain length. Values of the distribution coefficients are in general agreement with a simple extension of a model for excluded volume effects (the “available volume model”) which was applied previously to the distribution of proteins in this system. The current results therefore provide a second set of examples for molecules of very different geometry where the distribution of added molecules is controlled by excluded volume interactions between those molecules and the PEG 8000 of the two‐phase system. © 1992 John Wil

ISSN:0006-3525    

DOI:10.1002/bip.360321010

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractUnder physiological conditions, many polypeptide chains spontaneously fold into discrete and tightly packed three‐dimensional structures. The folded polypeptide chain conformation is believed to represent a minimum Gibbs energy of the system, governed by the weak interactions that operate between the amino acid residues and between the residues and the solvent.A semiempirical molecular thermodynamic model is proposed to represent the Gibbs energy of folding of aqueous homopolypeptide systems. The model takes into consideration both the entropy contribution and the enthalpy contribution of folding homopolypeptide chains in aqueous solutions. The entropy contribution is derived from the Flory‐Huggins expression for the entropy of mixing. It accounts for the entropy loss in folding a random‐coiled polypeptide chain into a specific polypeptide conformation. The enthalpy contribution is derived from a molecular segment‐based Non‐Random Two Liquid (NRTL) local composition model [H. Renon and J. M. Prausnitz (1968)AIChE J., Vol. 14, pp. 135–142; C.‐C. Chen and L. B. Evans (1986)AIChE J., Vol. 32, pp. 444–454], which takes into consideration of the residue‐residue, residue‐solvent, and solvent‐solvent binary physical interactions along with the local compositions of amino acid residues in aqueous homo‐polypeptides. The UNIFAC group contribution method [A. Fredenslund, R. L. Jones, and J. M. Prausnitz (1975)AIChE J., 21, 1086–1099; A. Fredenslund, J. Gmehling, and P. Rasmussen (1977)Vapor‐Liquid Equilibrium Using UNIFAC, Elsevier Scientific Publishing Company, Amsterdam], developed originally to estimate the excess Gibbs energy of solutions of small molecules, was used to estimate the NRTL binary interaction parameters.The model yields a hydrophobicity scale for the 20 amino acid side chains, which compares favorably with established scales [Y. Nozaki and C. Tanford (1971)Journal of Biological Chemistry, Vol. 46, pp. 2211–2217; E. B. Leodidis and T. A. Hatton (1990)Journal of Physical Chemistry, Vol. 94, pp. 6411–6420]. In addition, the model generates qualitatively correct thermodynamic constants and it accurately predicts thermodynamically favorable folding of a number of aqueous homopolypeptides from random‐coiled states into α‐helices. The model further facilitates estimation of the Zimm‐Bragg helix growth parameter s and the nucleation parametersfor amino acid residues [B. H. Zimm and J. K. Bragg (1959)Journal of Chemical Physics, Vol. 31, pp. 526–535]. The calculated values of the two parameters fall into the ranges suggested by Zim

ISSN:0006-3525    

DOI:10.1002/bip.360321011

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY