摘要:

AbstractThe presence of the sulfur atom of the methionine side chain exerts significant effects at different levels on biochemical behavior of chemotacticN‐formylpeptides. In order to acquire more information on this point, the synthesis, the conformation in the crystal, and the activity of For‐Hse(Me)‐Leu‐Phe‐OMe(2)—an oxygen analogue of For‐Met‐Leu‐Phe‐OMe (f MLP‐OMe) containing theO‐methyl‐L‐homoserine in place of the native methionine at position 1—is reported. The new analogue2adopts a conformation that is extended at the first two residues and folded at theC‐terminal phenylalanine. This conformation is different from that of the parent f MLP‐OMe and strikingly similar to that adopted by f MLP‐OBut. The side‐chain spatial orientation of2corresponds to that adopted by f MLP‐OH when cocrystallized with an immunoglobulin possessing binding properties similar to those of neutrophil receptors. When tested on human neutrophils the formylpeptide2is more active than the parent in the stimulation of directed mobility and maintains both the granule enzyme release activity an the superoxide anion

ISSN:0006-3525    

DOI:10.1002/bip.360340102

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

年代:1994

数据来源: WILEY

摘要:

AbstractαD‐N‐acetyl neuraminic acid (Neu5Ac, sialic acid) is a commonly occurring carbohydrate residue in various cell surface glycolipids and glycoproteins. This residue is linked terminally or internally to Gal residues via an α(2 → 3) or α(2 → 6) linkage. In the cell surface receptor, sialyl‐LewisX, a terminal α(2 → 3) linkage is present. Previous studies from our laboratory have shown that in solution LewisXadopts a relatively rigid structure. In order to model the Neu5Ac residue, vacuum molecular dynamics of this monosaccharide were compared with simulations that explicitly include solvent water. The dynamical average of the monosaccharide conformation obtained from the two simulations was similar. Vacuum calculations for the disaccharide Neu5Ac α(2 → 3) Gal β‐O‐methyl show that a number of low energy minima are accessible to this disaccharide. Molecular dynamics simulations starting from the low energy minima show conformational transitions with a time scale of 10–50 ps among several of the minima while large barriers between other minima prevent transitions on the time scale studied. Simulations of this disaccharide in the presence of solvent show fewer conformational transitions, illustrating a dampening effect of the solvent that has been observed in some other studies. Our results are most consistent with an equilibrium among multiple conformations for the Neu5Ac α(2 → 3) Gal β linkage

ISSN:0006-3525    

DOI:10.1002/bip.360340103

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

年代:1994

数据来源: WILEY

摘要:

AbstractA tetrasaccharide related to the blood group oligosaccharides, known as sialyl LewisX, has been proposed as the receptor for the lectin responsible for leukocyte adhesion named alternatively as E‐selectin or ELAM‐1. The13C‐ and1H‐nmr spectra have been completely assigned for a tetrasaccharide model of this receptor, Neu5Ac α‐(2 → 3)‐Gal β‐(1 → 4)‐[ Fuc α‐(1 → 3)‐] GlcNAc β‐NHAc. Quantitative nuclear Overhauser data (NOESY) have been recorded and analyzed by a complete spin matrix simulation method. Conformational space was exhaustively searched and all conformational models whose simulated NOESY spectra matched the experiment were found. Molecular mechanics and molecular dynamics calculations were carried out to test whether the experimental conformations are low energy and thus likely to represent true single conformations for the tetrasaccharide. It was concluded that while the LewisXtrisaccharide portion of the compound adopts a single conformation, there is likely to be some flexibility about the Neu5Ac α‐(2 → 3)‐linkage. A model featuring fast exchange between two different conformations of this linkage is found to be consistent with both the nmr experiments and the molecular dynamics si

ISSN:0006-3525    

DOI:10.1002/bip.360340104

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

年代:1994

数据来源: WILEY

摘要:

AbstractA DNA trefoil (31) knot has been constructed from a 104‐nucleotide molecule whose strands form a 3‐arm branched junction motif. This construction tests the notion that a node in a DNA knot can be equated with a half‐turn of double‐helical DNA, and is consistent with that concept. Of five 104‐mer sequences tested, only one produces high yields of the target knot. The other molecules produce larger quantities of circular material and of a knot containing more nodes. The key features that differentiate the successful design from the others are (1) the ligation takes place in the linker region between helical domains and (2) only six nucleotide pairs are used for each of the double‐helical arms of the junction. The successful design separates the double‐helical regions from each other by a spacer containing two deoxythymidine nucleotides at the site of the branched junction. © 1994 John W

ISSN:0006-3525    

DOI:10.1002/bip.360340105

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

年代:1994

数据来源: WILEY

摘要:

AbstractThe solution structure of crambin has been refined using a direct nuclear Overhauser effect (NOE) simulation approach (DINOSAUR) following a slow‐cooling simulated annealing protocol starting from eight previously obtained nmr and the x‐ray structures of crambin. Theoretical NOE intensities calculated with inclusion of local motions were directly compared to the experimental nmr data and forces were derived using a simple first‐order approximation for the calculation of the NOE gradient. A dynamic assignment procedure was applied for the peaks involving unassigned diastereotopic proton pairs or equivalent aromatic protons. With this approach,Rfactors could be minimized in a reasonable simulation time to low values (around 0.26) while deviations from ideal bond lengths and angles are still acceptable. The improvement inRfactors is accompanied by an improvement of the precision of the structures, the rms deviations (rmsd; from the average) calculated on the ensemble of nine structures decreasing from 0.65 to 0.55 Å for backbone atoms and from 1.0 to 0.85 Å for all heavy atoms. The solution structure is significantly different from the x‐ray structure with rmsd for all atoms of 1.35 Å compared to 0.85 Å between solution structures. The largest differences are found for residues Thr‐21 and Pro‐22 in the loop region between the two α‐helices and for the side chain of Tyr‐29. © 1994

ISSN:0006-3525    

DOI:10.1002/bip.360340106

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

年代:1994

数据来源: WILEY

摘要:

AbstractThe properties of collagen are affected by the replacement of Pro by imino acid analogues. The structural effect of the low‐level local substitution ofL‐azetidine‐2‐carboxylic acid (Aze) has been analyzed by computing the energy of CH3CO‐(Gly‐Pro‐Pro)4‐NHCH3triple helices in which a single residue of one strand has been replaced by Aze. When Aze is in position Y of a (Gly‐X‐Y) unit, low‐energy local deformations are introduced in the triple helix, i.e., it becomes more flexible. On the other hand, the flexibility of the triple helix is not increased with Aze in position X. The energy of the triple helix to coil transition is not changed significantly by this amount of substitution. In an earlier study, we have demonstrated that the regular substitution of Aze in every tripeptide distorts or destabilizes the triple helix to a large extent [A. Zagari, G. Némethy,&H. A. Scheraga (1990)Biopolymers, Vol. 30, pp. 967–974 ]. Thus, it appears that a high level of substitution is required to cause the observed chemical and biological effects of Aze on collagen. ©

ISSN:0006-3525    

DOI:10.1002/bip.360340107

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

年代:1994

数据来源: WILEY

摘要:

AbstractThe interaction of a series of 2‐phenylquinoline derivatives with RNA was investigated by means of viscometric, pKa, spectroscopic, binding,Tm, and kinetic methods. Compounds1,2, and3have a piperazyl substituent at thepara,meta, ororthoposition, respectively, while4has an unsubstituted phenyl ring. The pKa results suggest that1has three charges,2and3have more than two charges, and4has two charges at pH 6.2. Spectroscopic andTmresults indicate that1binds more strongly to RNA than2–4. Kinetic and modeling results indicate that1is a threading intercalator while2and4are classical intercalators. All experimental results indicate that3, which has a large twist between the phenyl and quinoline rings, binds weakly with RNA. © 1994 John Wiley&Sons,

ISSN:0006-3525    

DOI:10.1002/bip.360340108

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

年代:1994

数据来源: WILEY

摘要:

AbstractThe conformational transition between the α‐ and 310‐helical states of α‐methylalanine homopeptides is studied with molecular mechanics. Conformational transition pathways for Ace‐(MeA)n‐NMe withn= 7, 9, and 11 are obtained with the algorithms of Elber and co‐workers [R. Czerminski&R. Elber (1990)International Journal of Quantum Chemistry, Vol. 24, pp. 167–186; A. Ulitsky&R. Elber (1990)Journal of Chemical Physics, Vol. 92, pp. 1510–1511]. The free energy surface, or potential of mean force, for the conformational transition of Ace‐(MeA)9‐NMe is calculated from molecular dynamics simulations, and a method is presented for the decomposition of the free energy surface into the constituent energetic and entropic terms, via the calculation of the required temperature derivativesin situ. For the AMBER/OPLS model employed here, the conformational transition pathways each contain a single 310‐helical‐like transition state, and the transition state potential energy relative to the 310‐conformation is 3 kcal/mol, independent of peptide length. Entropic stabilization in the barrier region significantly lowers the activation free energies for the forward and reverse transitions from the estimates of the barrier heights based simply on potential energy alone.

ISSN:0006-3525    

DOI:10.1002/bip.360340109

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

年代:1994

数据来源: WILEY

摘要:

AbstractWe have studied by Raman and ir spectroscopy the structure of self‐associated polyinosinic acid and polyguanylic acid in aqueous solution. The results are consistent with the formation of a four‐stranded complex, which melts cooperatively near 60°C in the case of poly (I) in the presence of K+ions. The conformation of the ribose in both systems is mixed C2′‐endo/C3′‐endo, giving a structure that is intermediate between the extremes proposed previously from x‐ray diffraction studies. Characteristic Raman bands for the C2′‐endoribose conformation in polyribonucleotides are identified. The four‐stranded structure of poly (I) appears to be very flexible, with ≈15% of the tetrameric segments being disrupted and ≈30% of the ribose units adopting a disordered conformation prior to melting. This disordering process increases to ≈75% above the melting transition, with the remaining ≈25% of the ribose units keeping an ordered C2′‐endoor C3′‐endoconfo

ISSN:0006-3525    

DOI:10.1002/bip.360340110

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

年代:1994

数据来源: WILEY

摘要:

AbstractPoly(L‐lysine) having dansyl (5‐dimethylamino‐1‐naphthalene‐sulfonyl) groups to its side chains was prepared. The fluorescence spectra and fluorescence anisotropy ratios of the dansyl (DNS) group were measured in various conditions. In aqueous solution the increase in emission intensity was observed reflecting the alkali‐induced coil‐to‐helix transition. In aqueous‐methanolic solutions with methanol content above 60 wt %, the poly(L‐lysine) with DNS group (DNS‐PLL) was probed to show α‐helical conformation from CD spectra. With addition of alkali, the increase in fluorescence intensity of α‐helical DNS‐PLL and the drastic change in fluorescence anisotropy ratio were observed. In this case the rotational mobility of DNS probe decreases, gives a minimum at a certain concentration of added alkali, and then increases again up to approximately the initial level. At the concentration where the rotational mobility gives the minimum, intensity of scattered light gives a maximum. This shows that suppression of the mobility of DNS side chains is caused by the intermolecular aggregation of α‐helical DNS‐PLL. This concentration of added alkali corresponds to the midpoint of neutralization to charged side chains of the DNS‐PLL. The interaction that causes aggregate of α‐helical DNS‐PLL is suggested to be the intermolecular hydrogen bonding between neutralized and unneutralized

ISSN:0006-3525    

DOI:10.1002/bip.360340111

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

年代:1994

数据来源: WILEY