bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carrier design: Conformational studies of amino acid (X) and oligopeptide (X‐DL‐Alam) substituted poly(L‐lysine)
Authors: Mezö G. , Kajtár J. , Hudecz F. , Szekerke M. 
Published: December 2004

AbstractThe present study was undertaken to examine the influence of the reversal of the sidechain sequential order on the conformation of branched polypeptides. At the same time, the influence of the optically active amino acid joined directly to the poly (L‐Lys) backbone and the DL‐Ala oligomer grafted as chain‐terminating fragment were separately analyzed. Therefore two sets of polypeptides were synthesized corresponding to the general formula poly [Lys‐(Xi,)] (XK) and poly[Lys‐(DL‐Alam‐Xi)] (AXK) when X = Ala, D‐Ala, Leu, D‐Leu, Phe, D‐Phe, Ile, Pro, Glu.,D‐Glu, or His. For coupling amino acid X to polylysine, three types of active ester methods were compared: the use of pentafluorophenyl or pentachlorophenyl ester, and the effect of the addition of an equimolar amount of 1‐hydroxybenzotriazole. After cleavage of protecting groups, AXK polypeptides were synthesized by grafting short oligo (DL‐Ala) chains to XK by using N‐carboxy‐DL‐Ala anhydride. The CD measurements performed in water solutions of various pH values and ionic strengths were used for classification of the polypeptide conformations as either ordered (helical) or unordered. Different from what was observed with the unsubstituted poly (L‐Lys), poly[Lys‐(Xi)] type polypeptides can adopt ordered structure even under nearly physiological conditions (pH 7.3, 0.2M NaCl). These data suggest that the introduction of amino acid residue with either (ar) alkyl side chain (Ala, Leu, Phe) or negatively charged side chain (Glu) promotes markedly the formation of ordered structure. Comparison of chiroptical properties of poly [Lys‐ (DL‐Alam‐Xi)] and of poly [Lys‐ (Xi)] reveals that side‐chain interactions play an important role in the stabilization of ordered solution conformation of AXK type branched polypeptides. The results give rather conclusive evidence that not only hydrophobic interactions, but also ionic attraction, can be involved in the formation and stabilization of helical conformation of branched polypeptides. © 1993 John Wiley & Sons, Inc.
Nmr and computer‐aided modeling studies of the interactions between a cyclic hexapeptide and the two enantiomers of some Boc‐ and Fmoc‐amino acids
Authors: McEwen I. 
Published: December 2004

AbstractThe cyclic hexapeptide cyclo[‐Pro1‐Gly2‐Glu3(OBzl) ‐Pro4‐Phes5‐Leu6‐] (1) was modeled and synthesized to be used for chiral discrimination studies. Total correlated spectroscopy and nuclear Overhauser effect spectroscopy spectra of the cyclic hexapeptide 1 in CDCl3 showed the presence of three stereoisomers: two dominant stereoisomers 1a and 1b that exchanged chemically with each other, and a minor stereoisomer 1c (4%) that exchanged exclusively with the stereoisomer 1b. Of the two dominant stereoisomers, only 1a interacted specifically with t‐butyloxycarbonyl (Boc‐) and 9‐flourenylmethyloxycarbonyl (Fmoc‐) amino acids in CDCl3. The interaction site of la when complexing with the derivatized amino acids was the chain segment Phe5‐Leu6. The Phe5 NH and Leu6 NH protons are contiguous and solvent exposed. Their nmr signals shifted strongly downfield with the addition of Boc‐ or Fmoc‐ amino acids to the peptide solution. Thus, both NH protons hydrogen bond to the amino acids, forming a two‐point hydrogen‐bonding complex. The peptide stereoisomer 1b did not interact specifically with the Boc‐ and Fmoc‐amino acids because of the lack of two contiguous and solvent‐exposed peptidic NH protons that seem to be needed for specific interactions of the cyclic hexapeptide 1 with the Boc‐ and Fmoc‐amino acids. A clear difference in the interaction of 1a with D‐ and L‐enantiomers of BocTrp and Fmoc‐Trp was observed with nmr spectroscopy. Docking models and molecular mechanics calculations together with nmr observations showed that the NH proton of the indole ring of the Boc‐L‐Trp and the Fmoc‐L‐Trp hydrogen bonded to the Pro1 carbonyl group. In this three‐point hydrogen‐bonding complex, the indole ring becomes locked underneath the Leu residue. The nmr signals of all the Leu6 protons (except for Leu NH) shifted strongly upfield owing to the shielding effect of the indole aromatic ring currents. The indole NH of the D‐enantiomer did not hydrogen bond to the Pro1 carbonyl group because the formation of such a three‐point hydrogen‐bonding complex was thermodynamically unfavorable. © 1993 John Wiley & Sons, Inc.
Sequence dependence of purine C8H exchange kinetics in the dodecamer 5′‐d(CGCGAATTCGCG)‐3′
Authors: Walters Kylie J. , Russu Irina M. 
Published: December 2004

AbstractProton nmr spectroscopy is used to measure the deuterium exchange rates of C8 protons in individual purines of the dodecamer 5′‐d(CGCGAATTCGCG)‐3′ and their temperature dependence. In perfect agreement with results from tritium labeling and laser Raman spectroscopy, we find that the DNA secondary structure retards the rates of purine C8H exchange. The largest effects are observed for the C8 protons of adenines whose rates of exchange at 40°C are 3‐to 4‐fold lower than that in 5′‐adenosine monophosphate. Moreover, the retardation of exchange at the central adenine is greater than that at its 5′‐neighbor. For the guanines, the exchange rates are up to 2‐fold lower than that in 5′‐guanosine monophosphate, and the largest retardation is observed for the bases at positions 10 and 12. A dependence on base sequence is also observed for the activation energy for exchange. The activation energy is largest for the adenines and its value is 4 kcal/mol higher than that in 5′‐adenosine monophosphate. The lowest activation energy is observed for the guanine in position 4 and the value is the same as in 5′‐guanosine monophosphate. These results demonstrate the sensitivity of the purine C8H exchange kinetics to sequence‐dependent conformational features of B‐DNA in solution state. © 1993 John Wiley & Sons, Inc.
Probing the influence of sequence‐dependent interactions upon α‐helix stability in alanine‐based linear peptides
Authors: Jacchieri Saul G. , Richards Nigel G. J. 
Published: December 2004

AbstractThe observation that short, linear alanine‐based polypeptides form stable α‐helices in aqueous solution has allowed the development of well‐defined experimental systems with which to study the influence of amino acid sequence upon the stability of secondary structure. We have performed detailed conformational searches upon six alanine‐based peptides in order to rationalize the observed variation in the α‐helical stability in terms of side‐chain‐backbone and side‐chain‐side‐chain interactions. Although a simple, gas‐phase, potential model was used to obtain the conformational energies for these peptides, good agreement was obtained with experiment regarding their relative α‐helical stabilities. Our calculations clearly indicate that valine, isoleucine, and phenylalanine residues should destabilize the α‐helical conformation when included within alanine‐based peptides because of energetically unfavorable side‐chain‐backbone interactions, which tend to result in the formation of regions of 310‐helix. In the case of valine, the destabilization most probably arises from entropic effects as the isopropyl side chain can assume more orientations in the 310‐helical form of the peptide. A detailed examination of very short‐range interactions in these peptides has also indicated that an interaction, involving fewer than five consecutive residues, whose stabilizing effect reinforces that of the (i, i + 4) hydrogen bond may be the basis of the requirement for increased nucleation (σ) and propagation parameters (s) required by Zimm–Bragg theory to predict the α‐helical content for compounds in this class of short peptides. Our calculations complement recent work using modified Zimm–Bragg and Lifson–Roig theories of the helix–coil transition, and are consistent with molecular dynamics simulations upon linear peptides in aqueous solution. © 1993 John Wiley & Sons, Inc.
Nmr and molecular dynamics study of four carbocyclic muramyl dipeptide analogues
Authors: Pristovšek P. , Kidrič J. , Mavri J. , HadžI D. 
Published: December 2004

AbstractWe have performed a conformational analysis of the carbocyclic muramyl dipeptide analogues (1′R, 2′R)‐ and (1′S, 2′S)‐N‐[2‐(2′‐acetamidocyclohexyIoxy)acetyl]‐LAla‐D‐iGln (‐D‐Glu) utilizing 1H‐nmr spectroscopy and nuclear Overhauser effect restrained molecular dynamics. Intramolecular H bonding for all four diastereoisomers is suggested by the Ala‐NH temperature coefficients. Distance restraints were obtained by NOE spectroscopy and rotating frame NOE spectroscopy experiments. Structures with low potential energy and high agreement with NOE data were sought by restrained molecular dynamics. The ring configuration was found to induce conformational preferences. The β‐like turn characterized by the intramolecular C10 H‐bond Ala‐NH‐acetamido‐CO is preferred with the (1′S, 2′S), but appears to be less stable with (1′R, 2′R), diastereoisomers. Calculations show the double β‐turn proposed for muramyl dipeptide [S. Fermandjian, B. Perly, M. Level, and P. Lefrancier (1987) Carbohydrate Research, Vol. 162, pp. 23–32] to have higher potential energy. © 1993 John Wiley & Sons, Inc.
The contribution of helical potential to the in vitro receptor binding activity of a neuropeptide Y N‐terminal deletion fragment
Authors: Doughty Michael B. , Hu Longqin 
Published: December 2004

AbstractIn its dimeric form neuropeptide Y (NPY) folds into a compact structure in which the antiparallel oriented proline and α‐helices apparently associate to form a primitive hydrophobic core. To investigate the contribution of helical stability to the receptor binding activity of NPY and its N‐terminal deletion fragments, we synthesized and studied the solution conformational properties and in vitro activities of NPY, Nα‐acetyl‐NPY2–36, NPY15–36, Nα‐propinonly‐NPY15–36, and Nα‐succinyl‐NPY15–36 is significantly less helical than both NPY and Nα‐acetyl‐NPY2–36, and this decreased helical potential is attributed of the absence of the intramolecular stabilizing interaction afforded by the proline helix in the latter analogues. However, in accord with the helix dipole model, the helical potential of NPY15–36 is significantly increased by N‐terminal succinlyation, whereas propionylation has no effect. In addition to an increase in helical potential, Nα‐succinyl‐NPY15–36 is 2.5 and 4.6 times more active than NPY15–36 and Nα‐propionly‐NPY15–36, respectively and is equipotent with Nα‐acteyl‐NPY2–36 in displacing 1mM[3H]‐NPY from specific binding sites in rat brain membranes. The demonstration of positive correlation between % α‐helix content and in vitro binding activity suggests that the helical potential of N‐terminal NPY deletion fragments contributes to their in vitro activity in the rat brain, and that a second role of the proline helix might be to stabilize the receptor‐active conformation of the NPY α‐helix. © 1993 John Wiley & Sons, Inc.
Stretching and overstretching of DNA in pulsed field gel electrophoresis. I. A quantitative study from the steady state birefringence decay
Authors: Mayer Pascal , Sturm Jean , Weill Gilbert 
Published: December 2004

AbstractUsing a sensitive birefringence instrument, the birefringence arising from the orientation of the DNA chain during electrophoretic transport has been recorded. This birefringence is shown to proceed both from the alignment (stretching) of the molecule in the direction of the electric field and from the extension of the length of its primitive path (overstretching). The contribution of these two processes can be separated in the decay of the birefringence after the end of the application of the electric field. The fast relaxation of the overstretching occurs first and is demonstrated to be the main contribution to the birefringence. The orientation factor of the remaining stretched state and its decay can be quantitatively understood using the biased reptation model. It provides, in addition, a high value for the tube diameter or gel pore size a (4500 ± 450 Å for a 0.7% agarose gel with a c−0.6g dependence in the agarose concentration cg) and a low value for the effective charge per base pair (0.2e as compared to 0.5e using the condensation hypothesis). The contribution of overstretching to the birefringence is also quantitatively interpreted in term of the change in the mean length l of DNA inside a pore size a. The dynamics of decay of this overstretching is well represented by a stretched exponential with a stretching exponent α = 0.44. The mean decay time decreases slightly with increasing fields and scales with the overall DNA length close to N20. © 1993 John Wiley & Sons, Inc.
A formulation for correlating properties of peptides and its application to predicting human immunodeficiency virus protease‐cleavable sites in proteins
Authors: Chou James J. 
Published: December 2004

AbstractA mathematical frame has been established to generally formulate the correlating properties of peptides. The formulation can be used to study the specificity of multisite enzymes, particularly in predicting the susceptible sites in proteins by human immunodeficiency virus (HIV) proteases, and hence can serve as a supplementary means in designing HIV protease inhibitors as potential drugs against acquired immunodeficiency syndrome. © 1993 John Wiley & Sons, Inc.
Effect of various frictional models on long‐time peptide dynamics
Authors: Kostov Konstantin , Freed Karl F. , Perico Angelo 
Published: December 2004

AbstractWe analyze the implications of various choices for atomic friction coefficients on a recent theory of long‐time peptide dynamics. One method for determining atomic friction coefficients is based on calculating effective hydrodynamic radii from the reduction of the atomic surface area accessible to solvent, while another employs an additive van der Waals radii model. These friction coefficients are used to evaluate the orientational correlation times of bonds in the peptide fragment ACTH(5–10), which contains a single tryptophan probe. Three models are considered; they choose as relevant slow variables (a) the positions of the α‐carbons, (b) the positions of all backbone bonds, and (c) both positions in (b) and those along side chains. Comparisons are made between the three models and with experiment. While general variations are similar, large shifts in local correlation times emerge from using the different methods. The results indicate that the extra backbone bonds do not contribute much to the memory function for the virtual bond model, but the side‐chain groups have a strong effect. © 1993 John Wiley & Sons, Inc.
Simulation of α‐helix–coil transitions in simplified polyvaline: Equilibrium properties and brownian dynamics
Authors: Schneller William , Weaver David L. 
Published: December 2004

AbstractA quantitative understanding of helix–coil dynamics will help explain their role in protein folding and in folded proteins. As a contribution to the understanding, the equilibrium and dynamical aspects of the helix–coil transition in polyvaline have been studied by computer simulation using a simplified model of the polypeptide chain. Each amino acid residue is treated as a single quasiparticle in an effective potential that approximates the potential of mean force in solution. The equilibrium properties examined include the helix–coil transition and its dependence on chain position and well depth at the coil–helix interface. A stochastic simulation of the Brownian motion of the chain in its solvent surroundings has been used to investigate dynamical properties. Time histories of the dihedral angles have been used to study the behavior of the helical structure. Auto and cross‐correlation functions have been calculated from the time histories and from the state (helix or coil) functions of the residues with relaxation times of tens to hundreds of picoseconds. Helix–coil rate constants of tens of ns−1 were found for both directions of the transition. © 1993 John Wiley & Sons, Inc.
Molecular dynamics analysis of a ribonuclease C‐peptide analogue
Authors: Soman Kizhake V. , Karimi Afshin , Case David A. 
Published: December 2004

AbstractWe have carried out a nanosecond molecular dynamics simulation of an analogue of the ribonuclease C‐peptide in water. The overall conformation has an extended region for the first three amino acids connected to an α‐helix for residues 4–13, and this basic structure is preserved throughout the simulation, with helical hydrogen bonds present 87% of the time, on average. The final helical hydrogen bond is spontaneously broken and re‐formed several times, providing a detailed picture of such winding/unwinding events. The simulation was used to estimate the effects of internal motion on proton nuclear Overhauser effect spectroscopy (NOESY) intensities for several classes of important cross peaks. Within the helical regions, the effects of internal motion vary only a little from one residue to another for backbone–backbone cross peaks, and the relevant correlation functions reach plateau values within about 50 ps. The spectral simulations show, however, that it may be difficult to establish a close quantitative connection between NOESY cross‐peak volumes and measures of helical content. © 1993 John Wiley & Sons, Inc.
Assessment of protein rotational diffusion by 13C off‐resonance rotating frame spin–lattice relaxation: Effect of backbone and side‐chain internal motion
Authors: Wang Sharon X. , Stevens Arthur , Schleich Thomas 
Published: December 2004

AbstractThe 13C off‐resonance rotating frame spin–lattice relaxation technique is applicable to the study of protein rotational diffusion behavior in a variety of experimental situations. The original formalism of James and co‐workers (1978) (J. Am. Chem. Soc. Vol. 100, pp. 3590–3594) incorporated random isotropic reorientational motion of a rigid spherical rotor with no provision for backbone or side‐chain carbonyl group internal motion. Here we demonstrate that the failure to include such internal motion may lead to erroneous rotational correlation time determinations for overall reorientational motion. The effect becomes severe for protein molecular masses in excess of 100 kD. Inclusion of both backbone and side‐chain carbonyl carbon internal motion, using reasonable parameters derived from the literature [R. Levy and M. Karplus (1979), Chemical Physics Letters, Vol. 65, pp. 4–11; G. Careri, P. Fasella, and E. Gratton (1975), Critical Reviews in Biochemistry, Vol. 3, pp. 141–164; G. Lipari, A. Szabo, and R. Levy (1982), Nature, Vol. 300, pp. 197–198], plus corrections for anisotropic tumbling [C. F. Morgan, T. Schleich, G. H. Caines, and D. Michael (1990), Biopolymers, Vol. 29, pp. 469–480] and microscopic viscosity [S. H. Koenig (1980), ACS Symposium. Series, Vol. 127, pp. 157–176], leads to reliable values for the correlation time describing overall protein reorientation up to molecular masses of approximately 1000 kD. © 1993 John Wiley & Sons, Inc.
Comparative study of the interactions of cisplatin and carboplatin with nucleotides using UV resonance raman spectroscopy
Authors: Benson Ronda L. , Gustafson Terry L. 
Published: December 2004

AbstractWe have obtained the UV excited resonance Raman spectra of five mononucleotides bound to cisplatin and to carboplatin using excitation in resonance with the first electronic absorption bands of the nucleotide bases. Substantial changes in the spectra are observed following interaction with both platinum drugs, indicating modifications to nucleotide structure. Pt (II) binds to base portions of the nucleotide molecules, altering their normal modes of vibration significantly. We present comparative data of cisplatin and carboplatin, and discuss the implications of these results. The kinetics of the drug/nucleotide reactions differ, but final products are found to be similar. © 1993 John Wiley & Sons, Inc.
Conformation and interactions of bombolitin I analogues with SDS micelles and phospholipid vesicles: CD, fluorescence, two‐dimensional NMR and computer simulations
Authors: Chorev Michael , Gurrath Marion , Behar Vered , Mammi Stefano , Tonello Antonella , Peggion Evaristo 
Published: December 2004

AbstractBombolitins are five structurally related heptadecapeptides acting at the membrane level able to lyse erythrocytes and liposomes and to enhance the activity of phospholipase A 2(PLA2). In the presence of SDS or phospholipid vesicles bombolitins are able to form amphiphilic α‐helical structures and this property seems to be the major determinant of bioactivity. In order to test the model of interaction between bombolitin I and membranes, an analogue was synthesized in which all the lysines were replaced by arginines:

([Arg2,9,12, Ile10] bornbolitin I). The design ofthis sequence allowed the synthesis of a second analogue through a specijic postsynthetic dansylation at the ϵ‐amino group qf a lysine residue replacing the original leucine residue at position 7. The, first analogue was, fiilly characterized by CD and two‐dimensional nmr in the presence of SDS or phospholipid vesicles. The peptide, folds into an amphiphilic α‐helical confbrrnation with the helical segment spanning the central part of the sequencefrom Ile3 to His16. This behavior is identical to that observed for the native sequence. The replacement of Iysine residues by arginine hus no detectable effect on the conformational prderence of the peptide chain. By CD and fluorescence spectroscopy measurements, the fluorophore‐containing analogue [Arg2,9,12, Lys7(ϵ‐dansyl)] bombolitin I also folded into the α‐helical conformation in the presence of SDS micelles or phospholipid vesicles. In particular, the dansyl fluorophore, which is located approximately in the middle of the apolar surface ojthe amphiphilic helix, is clearly buried in a hydrophobic environment when the peptide is bound to phospholipid vesicles. These findings support the hypothesis that the peptide helices are oriented parallel to the vesicle surface. © 1995 John Wiley & Sons, Inc.
Conformation of parathyroid hormone antagonists by CD, nmr, and molecular dynamics simulations
Authors: Chorev Michael , Behar Vered , Yang Quming , Rosenblatt Michael , Mammi Stefano , Maretto Stafano , Pellegrini Maria , Peggion Evaristo 
Published: December 2004

AbstractThe conformation of two highly potent parathyroid hormone (PTH) antagonists was investigated in water/2, 2, 2‐trifluoroethanol mixtures. The two peptides are derived from the sequence (7‐34) of PTH and of PTH‐related protein (PTHrP) and have a D‐Trp replacing Gly in position 12. In the analogue derived from PTHrP, Lys11 was replaced by Leu to remove the residual agonist activity. The study was conducted by CD and two‐dimensional proton magnetic resonance spectroscopy, and the nuclear Overhauser effects found were utilized in restrained distance geometry and molecular dynamics simulations.Both peptides adopt a helical C‐terminal conformation, which seems more stable in the case of the PTHrP analogue. A type II′ β‐turn centered around D‐Trp12 and Lys13 is present inboth structures. © 1995 John Wiley & Sons, Inc.