摘要:

AbstractPoly(hydroxyalkyl‐L‐glutamine) (alkyl = ethyl, propyl, butyl) solutions have been studied by CD as functions of temperature and activity of calcium chloride and sodium perchlorate. Helical content is altered by changes in salt activity and temperature. The helicity of poly(hydroxybutyl‐L‐glutamine) and poly(hydroxypropyl‐L‐glutamine) falls to zero in a monotonic fashion with increasing calcium chloride activity. A nonzero helicity reappears at activities in excess of 5–50 mol kg−1. Poly(hydroxypropyl‐L‐glutamine) is much more sensitive to calcium chloride than is poly(hydroxybutyl‐L‐glutamine), and both polypeptides are more sensitive to calcium chloride than are typical proteins. Markedly different behavior is observed with sodium perchlorate. This salt acts as a helix stabilizer at low activities but becomes a destabilizer at activities higher than 0.3–1.0 mol kg−1. In this respect the effect of sodium perchlorate onnonionicpoly(hydroxyalkyl‐L‐glutamines) resembles that seen withcationicpoly(L‐lysine) and poly(L‐arginine). Helix stabilization at low sodium perchlorate activity is moderate for poly(hydroxybutyl‐L‐glutamine) and large for poly(hydroxypropyl‐L‐gl

ISSN:0006-3525    

DOI:10.1002/bip.1980.360191102

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

年代:1980

数据来源: WILEY

摘要:

AbstractEmpirical conformational energy calculations have been carried out for N‐methyl derivatives of alanine and phenylalanine dipeptide models and N‐methyl‐substituted active analogs of three biologically active peptides, namely thyrotropin‐releasing hormone (TRH), enkephalin (ENK), and luteinizing hormone‐releasing hormone (LHRH). The isoenergetic contour maps and the local dipeptide minima obtained, when the peptide bond (ω) preceding the N‐methylated residue is in thetransconfiguration show that (1) N‐methylation constricts the conformational freedom of both theith and (i+ 1)th residues; (2), the lowest energy position for both residues occurs around ϕ = −135° ± 5° and ψ = 75° ± 5°, and (3) the αLconformational state is the second lowest energy state for the (i+ 1)th residue, whereas for theith residue the C5(extended) conformation is second lowest in energy. When the peptide bond (ωi) is in thecisconfiguration theith residue is energetically forbidden in the range ϕ = 0° to 180° and ψ = −180° to +180°. Conformations of low energy for ωi= 0° are found to be similar to those obtained for thetranspeptide bond. In all the model systems (irrespective ofcisortrans), the αRconformational state is energetically very high. Significant deviations from planarity are found for the peptide bond when the amide hydrogen is replaced by a methyl group. Two low‐energy conformers are found for [(N‐Me)His2]TRH. These conformers differ only in the ϕ and ψ values at the (N‐Me)His2residue. Among the different low‐energy conformers found for each of the ENK analogs [D‐Ala2,(N‐Me)Phe4, Met5]ENK amide and [D‐Ala2,(N‐Me)Met5]ENK amide, one low‐energy conformer was found to be common for both analogs with respect to the side‐chain orientations. The stability of the low‐energy structures is discussed in the light of the activity of other analogs. Two low‐energy conformers were found for [(N‐Me)Leu7]LHRH. These conformations differ in the types of bend around the positions 6 and 7 of LHRH. One bend type is elimin

ISSN:0006-3525    

DOI:10.1002/bip.1980.360191103

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

年代:1980

数据来源: WILEY

摘要:

AbstractThelacrepressor and its tryptic core were studied by ir spectroscopy, and their β‐structure content was determined by analysis of the spectra. Using protein‐derived reference spectra, we find a β‐content forlacrepressor of 18% and of 23% for its tryptic core. The higher amount of β‐conformation in the tryptic core is confirmed by another type of analysis (decomposition of the spectra in Gaussian curves). These results are discussed with respect to their implications for the structure of the N‐terminal “headpiece” oflacrepressor and for the mode of interaction oflacrepressor

ISSN:0006-3525    

DOI:10.1002/bip.1980.360191104

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

年代:1980

数据来源: WILEY

摘要:

AbstractThe structural properties of uracil photohydrates at the monomer and dimer level in aqueous solution have been examined in detail by nmr spectroscopy. Based on such evidence, the absolute configurations of the two possible diastereomers have been assigned, and the conformational perturbations induced by photohydration have been evaluated. In all instances, photohydration shifts the2E ⇌3E puckering equilibrium of the sugar ring of the uridylyl fragment towards2E (from 12–18%). In addition, for both dimers examined in detail, ho6UpA and Apho6hU, the effect of dimerization on sugar pucker is such that the 3′‐terminal unit shows a clear increase in the percentage of3E (relative to the appropriate 5′‐mononucleotide), whereas the percentage3E of the 5′‐terminal unit shows no change. This is contrary to the findings in the normal dinucleoside monophosphates, where an increased preference for3E pucker occurs inbothresidues on dimerization and increased base stacking. Significant base–base interactions were observed in both hydrated dimers despite the loss of the planar π‐system in the uracil fragment. In addition, the rate of photohydration for a particular dimer pair (e.g., ApU and UpA or GpU and UpG) is shown to be inversely dependent on the amount of base stacking in the parent dimer. This latter parameter has also been correlated with the ratio of the two possible diastereomers formed in the reaction and is associated with a preferential attack at one face of the pyrimidine base ring. The shift of the sugar puckering equilibrium towards2E has been compared with similar shifts observed when adenosine and guanosine are methylated at N(1) and N(7), respectively. The possible biological significance of the above‐mentioned conformationa

ISSN:0006-3525    

DOI:10.1002/bip.1980.360191105

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

年代:1980

数据来源: WILEY

摘要:

AbstractIn proton nmr, the chemical exchange rates of slowly exchanging labile hydrogens (with lifetimes in the range ∼ 10 msec – ∼ 1 sec) of peptides, proteins, and nucleic acids can be measured in H2O by a combination of two separate experiments: (1) the transfer of solvent saturation and (2) saturation‐recovery experiments. When these molecules exist in a dynamic equilibrium among different conformations, the experiments cannot be analyzed in a straightforward manner to derive the intrinsic exchange rates. In the present study we have derived analytical expressions for the above two experiments on a biomolecule under certain limiting conditions: (1) the extreme low‐motility limit, where each of the conformational transitions is much slower than the corresponding hydrogen exchange rate with the solvent; (2) the high‐motility limit (EX2mechanism), which is the opposite extreme of the previous limit; and (3) the low‐motility limit (EX1mechanism), which is a mixture of limits (1) and (2), i.e., for some of the conformations, the exchange rate with the solvent is much faster than their conformational transition rates, while for the remaining conformations the reverse situation is realized. The results may be considered as a generalization to an arbitrary number of states of the two‐state model treated by Hvidt. Equations have also been derived that are applicable to the iostope exchange method of measuring very slow exchange rates (with life‐times of the order of minutes and longer) in biomolecules. The saturation recovery experiments performed in H2O on the active pentapeptide fragment of thymopoietin serve to illustrate the high‐motility limit. The theoretical formulation presented in this study can be easily adapted to other double‐resonance techniques and also to situations where the kinetics of an arbitrary system existing in a multistate equili

ISSN:0006-3525    

DOI:10.1002/bip.1980.360191106

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

年代:1980

数据来源: WILEY

摘要:

AbstractComplex formation of 1‐anilinonaphthalene‐8‐sulfonate (ANS) and 2‐p‐toluidinonaphthalene‐6‐sulfonate (TNS) with the β‐form of poly(L‐lysine) [(β‐Lys)n] has been studied by circular dichroism (CD) and absorption spectra measurements. Not only hydrophobic interactions but also hydrogen‐bonding and electrostatic interactions contribute to complex formation. The relative importance of these stabilizing factors depends on the relative position of the arylamino group and the sulfonate. For example, ionic interactions play a significant role in the binding of 1,8‐ANS and 1,8‐TNS, but not in the case of 2,6‐TNS. The induced CD of the complexes of (β‐Lys)nwith 1,8‐ANS and 1,8‐TNS is consistent with theoretical calculations for nonplanar conformations of these dyes, twisted in a left‐handed sense. As expected for steric reasons, the dominant isomer is one in which the arylamino group is oriented away from the 8‐sulfonate (α1). The induced CD of complexes with 2,6‐TNS can be accounted for by an equimolar mixture of left‐handed isomers in which the arylamino group is oriented toward the 1‐position (β2) and toward the 3‐position (β1). Our results demonstrate that (β‐Lys)nis capable of chiral discrimination and suggest its

ISSN:0006-3525    

DOI:10.1002/bip.1980.360191107

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

年代:1980

数据来源: WILEY

摘要:

AbstractA simplified model of a polypeptide chain is described. Each residue is represented by a single interaction center. The energy of the chain and the force acting on each residue are given as a function of the residue coordinates. Terms to approximate the effect of solvent and the stabilization energy of helix formation are included. The model is used to study equilibrium and dynamical aspects of the helix–coil transition. The equilibrium properties examined include helix–coil equilibrium constants and their dependence on chain position. Dynamical properties are examined by a stochastic simulation of the Brownian motion of the chain in its solvent surroundings. Correlations in the motions of the residues are found to have an important influence on the helix–coil transition

ISSN:0006-3525    

DOI:10.1002/bip.1980.360191108

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

年代:1980

数据来源: WILEY

摘要:

AbstractThe problem of adequately correcting thermal titration curves for heat losses in isoperibolic microcalorimeters during rapid reactions in small volumes has been examined. With a data‐acquisition system for the simultaneous encoding of changes in heat, pH, and time linked directly to a DEC‐20 computer, various possible mechanisms for heat‐loss corrections were tested using computer‐modeling techniques. Models expressed by series exponential terms, as commonly used in linear pharmacokinetics to describe the time‐course concentration of a drug, proved to be inadequate to reconstruct the “adiabatic” thermal curve, since its apparent magnitude increased with the time taken for its generation. However, models based on mechanisms incorporating at least two heat sinks, one of which can be equated to the surroundings, have proved successful. The differential equations descriptive of the various models examined have rate constants characteristic of the reaction cell and its inserts, the reaction volume, and the calorimeter used. These can be evaluated by a curve‐fitting algorithm (MLAB) using standard thermal‐titration data (the neutralization of HCL with KOH). Once the rate constants are known, the differential equation solver of MLAB is then used to deconvolute any time: heat‐change matrix to that which would obtain in the absence of heat loss (the “adiabatic” state). With an appropriate differential equation model, the magnitude of the corrected heat change is independent of the time taken for its production and so‐called best model(s) have been judged on the basis of Akaike's information criterion. The application of the heat‐loss correction procedure to the thermal titration of chym

ISSN:0006-3525    

DOI:10.1002/bip.1980.360191109

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

年代:1980

数据来源: WILEY

摘要:

AbstractBased on steric and electrostatic considerations, the prerequisites for binding to DNA via the intercalation mechanism are proposed. Steric contour energy curves are presented to demonstrate the region inaccessible to an intercalant. They are calculated with a 6‐n(n= 14) potential. This method is a soft potential analog of an excluded‐volume approach. Electrostatic contours on the steric surface illustrate the relatively positive and negative regions of the binding site. The principal intercalation sites, predicted to fit into B‐DNA via a tetramer‐duplex unit, and the unconstrained dimer‐duplex units, obtained in crystal structures, are examined. These contours illustrate the requirements of size, conformation, and net atomic charges necessary for intercalation and optimum binding. Based on the limited space available for intercalation by the presence of the backbone and the maximum base‐pair separation of 8.25 Å, an Essential Metabolite Exclusion Hypothesis

ISSN:0006-3525    

DOI:10.1002/bip.1980.360191110

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

年代:1980

数据来源: WILEY

摘要:

AbstractThe binding positions and relative minimum binding energies are calculated for complexes of 9‐aminoacridine, proflavine,N‐methylphenanthridinium, and ethidium in theoretically determined intercalation sites in B‐DNA (sites I and II) and in unconstrained dimer‐duplex sites. The selection of site I in B‐DNA by these compounds agrees with the theoretical interpretation of studies of unwinding angles in closed circular DNA in all cases but ethidium, which is predicted to select site II. The most stable binding positions of the acridines and ethidium in unconstrained dimer‐duplex units agree with experimental results of intercalation complexes of dinucleoside monophosphate units. Base‐pair specificity for Watson‐Crick pairing is examined. The energy of an intercalation complex is partitioned into ΔE23, the energy required to open base pairs BP2and BP3in B‐DNA to a site, and ΔEIn, the energy change when a free molecular intercalates. ΔE23depends strongly on the base‐pair sequence, whereas ΔEInfor the four molecules studied does not. The three most stable sequences contain (pyrimidine)p(purine) units, and this provides a rationale for the exclusive formation of crystals of intercalation complexes with these units. In spite of this selectivity, the distribution of GṁC and AṁT base pairs is equal for these three units and persists as the more unstable sequences are included. Therefore, specificity arises from the interaction between the base pairs and the 2′‐deoxyribose 5′‐monophosphate backbone for the opening of B‐DNA to an intercalation site and not from the interactio

ISSN:0006-3525    

DOI:10.1002/bip.1980.360191111

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

年代:1980

数据来源: WILEY