Antigen�Cantibody interactions of influenza virus hemagglutinin revealed by the fragment molecular orbital calculation

Effective interactions between amino acid residues in antigen?Cantibody complex of influenza virus hemagglutinin (HA) protein can be evaluated in terms of the inter-fragment interaction energy (IFIE) analysis with the fragment molecular orbital (FMO) method, in which each fragment contains the side chain of corresponding amino acid residue. We have carried out the FMO-MP2 (second-order Moeller?CPlesset) calculation for the complex of HA antigen and Fab antibody of influenza virus H3N2 A/Aichi/2/68 and obtained the IFIE values between each amino acid residue in HA and the whole antibody as the sums over the residues contained in the latter. Combining this IFIE data with experimental data for hemadsorption activity of HA mutants, we succeeded in theoretically explaining the mutations in HA observed after the emergence of influenza virus H3N2 A/Aichi/2/68 in an earlier study, except for those of THR83. In the present study, we employ an alternative way of fragment division in the FMO calculation at the carbonyl C site of the peptide bond instead of the C_?? site used in the previous work, which provides revised IFIE values consistent with all the historical mutation data in the antigenic region E of HA including the case of THR83 in the present prediction scheme for probable mutations in HA.     

Effect of the peptide secondary structure on the peptide amphiphile supramolecular structure and interactions

Bottom-up fabrication of self-assembled nanomaterials requires control over forces and interactions between building blocks. We report here on the formation and architecture of supramolecular structures constructed from two different peptide amphiphiles. Inclusion of four alanines between a 16-mer peptide and a 16 carbon long aliphatic tail resulted in a secondary structure shift of the peptide headgroups from α helices to β sheets. A concomitant shift in self-assembled morphology from nanoribbons to core-shell worm-like micelles was observed by cryogenic transmission electron microscopy (cryo-TEM) and atomic force microscopy (AFM). In the presence of divalent magnesium ions, these a priori formed supramolecular structures interacted in distinct manners, highlighting the importance of peptide amphiphile design in self-assembly.     

Analysis of chemical interactions between stabilized zirconia and perovskites

LaMnO₃-based perovskites are used as cathode materials in solid oxide fuel cells (SOFC). A major aspect for their applicability is their chemical inertness in connection with the electrolyte material YSZ (Zr_0.85Y_0.15O_1.93) against zirconate formations. Perovskites with the composition La_y-x(Sr, Ca)_xMn_1-uCo_uO₃ (y = 1.0 and 0.95; x = 0– 0.2 and 1; u = 0 and 0.2) were investigated with regard to their reactivity with YSZ at different reaction times and temperatures. Powder mixtures and double-layer reaction couples were used for the investigations. XRD phase analyses, SEM/EDX and EPMA were applied for the characterization of the annealed samples. La-deficient perovskites (y = 0.95) partially substituted by Sr and Ca improve the chemical compatibility of perovskite compositions towards YSZ. Sr-containing perovskites were found to have a higher reactivity than Ca perovskites for La₂Zr₂O₇ formation. On the other hand enhanced Ca diffusion into YSZ was observed. Co substitution on Mn lattice sites decreased the chemical compatibility, especially for Sr containing perovskites.     

Analysis of chemical interactions between stabilized zirconia and perovskites

LaMnO(3)-based perovskites are used as cathode materials in solid oxide fuel cells (SOFC). A major aspect for their applicability is their chemical inertness in connection with the electrolyte material YSZ (Zr(0.85)Y(0.15)O(1.93)) against zirconate formations. Perovskites with the composition La(y-x)(Sr, Ca)(x)Mn(1-u)Co(u)O(3) (y = 1.0 and 0.95; x = 0- 0.2 and 1; u = 0 and 0.2) were investigated with regard to their reactivity with YSZ at different reaction times and temperatures. Powder mixtures and double-layer reaction couples were used for the investigations. XRD phase analyses, SEM/EDX and EPMA were applied for the characterization of the annealed samples. La-deficient perovskites (y = 0.95) partially substituted by Sr and Ca improve the chemical compatibility of perovskite compositions towards YSZ. Sr-containing perovskites were found to have a higher reactivity than Ca perovskites for La(2)Zr(2)O(7) formation. On the other hand enhanced Ca diffusion into YSZ was observed. Co substitution on Mn lattice sites decreased the chemical compatibility, especially for Sr containing perovskites.     

Synthesis and structure of 1,4-dipiperazino benzenes: chiral terphenyl-type peptide helix mimetics

The terphenyl structure has been proven to be an ideal scaffold mimicking side-chain functionalities of peptidic alpha-helices. The synthesis of 1,4-dipiperazino benzenes, using stepwise transition metal-catalyzed N-arylation of chiral piperazines to a central benzene core is reported. The structure determination by X-ray crystallography reveals a geometrical arrangement of the hydrophobic side chains resembling the orientation of key i, i + 3, and i + 7 positions in a peptidic alpha-helix or in terphenyl helix mimetics.     

Investigation of the interactions between ginsenosides and amino acids by mass spectrometry and theoretical chemistry

In order to evaluate the essence of the interactions of ginsenosides and proteins which are composed by α-amino acids, electrospray ionization mass spectrometry was employed to study the noncovalent interactions between ginsenosides (Rb₂, Rb₃, Re, Rg₁ and Rh₁) and 18 kinds of α-amino acids (Asp, Glu, Asn, Phe, Gln, Thr, Ser, Met, Trp, Val, Gly, Ile, Ala, Leu, Pro, His, Lys and Arg). The 1:1 and 2:1 noncovalent complexes of ginsenosides and amino acids were observed in the mass spectra. The dissociation constants for the noncovalent complexes were directly calculated based on peak intensities of ginsenosides and the noncovalent complexes in the mass spectra. Based on the dissociation constants, it can be concluded that the acidic and the basic amino acids, Asp, Glu, Lys and Arg, bound to ginsenosides more strongly than other amino acids. The experimental results were verified by theoretical calculations of parameters of noncovalent interaction between ginsenoside Re and Arg which served as a representative example. Two kinds of binding forms, “head–tail” (“H–T”) and “head–head” (“H–H”), were proposed to explain the interaction between ginsenosides and amino acids. And the interaction in “H–T” form was stronger than that in “H–H” form.     

Probing the weak interactions between amino acids and carbon monoxide

The relatively weak interactions between some non-charged amino acids with CO were investigated theoretically by using density functional theory （DFT） method. The stretching frequency of CO correlates well with its bond length followed the Badger＇s rule, and the correlation between binding energy and Mulliken charge partition of CO was also investigated for the first time. 2007 Ying Wu Lin. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.     

Synthesis of C-terminal peptide fragments of the heavy chain of hemagglutinin of influenza virus of subtypes H1 and H3

It is proposed to use the chromogenic 2-[4-phenylazo)benzylsulfonyl]ethyl group, which can be eliminated by organic bases in aprotic solvents, for the protection of a C-terminal carboxy group in the synthesis of peptides. The synthesis of a number of 10–16-membered peptides corresponding to C-terminal fragments of the heavy chain of the hemagglutination of influenza virus of subtypes H1 and H3 has been performed with the use of this group.All-Union Scientific-Research Institute of Molecular Biology, Kol'tsovo, Novosibirsk Oblast. Vektor Scientific-Industrial Association, Ministry of the Medical and Biological Industry of the USSR, Novosibirsk. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 732–738, September–October, 1988.     

Effects of functional group interactions on the dissociation reactions of protonated amino alcohols

The dissociation reactions of protonated amino alcohols were examined in a quadrupole ion trap mass spectrometer. Multi-stage collision-induced dissociation techniques were used to characterize the ions and their fragments and to assist in the determination of the dissociation mechanisms. In addition, semi-empirical calculations were used to rationalize the results on the basis of the thermodynamics of the reactions in question. The reaction of special interest was the double elimination of water and ammonia. For this high-energy process, it is shown that the initial deamination step is the thermodynamically favored one in most cases. The enthalpies of formation for the various precursor and product ions and also those for some of the reaction intermediates were estimated using molecular modelling and semi-empirical calculation methods. The values obtained indicated that the minimum endothermicity of the sequential deamination–dehydration reaction ranges from 209 to 460 kJ mol^?1 for the compounds studied here. Moreover, protonation at the amine site was found to be energetically favored by 38–192 kJ mol^?1 over protonation at the hydroxyl site.     

Studies on the interactions between lactam analogs and the N-terminal extracellular tail of CC chemokine receptor 4 by CZE

CC chemokine receptor 4 (CCR4) is a kind of G-protein-coupled receptors with a characteristic seven-transmembrane structure and selectively expressed on Th2-type CD4+ T-cells, which play a pivotal role in allergic inflammation. In this study, the interactions between 2-(2-(2,4-dichloro-phenyl)-4-{[(2-methyl-3-chloro-phenyl)-1-ylmethyl]-carbamoyl}-methyl)-5-oxo-pyrrole-1-yl)-N-(3-piperidinyl-propyl)-acetamide (compound A), a known CCR4 antagonist, and ML40 were studied by CZE for the first time. Both qualitative and quantitative characterizations of the drug-peptide binding were determined. The binding constant of the interaction between the trans-diastereomer of compound A and ML40, calculated from the Scatchard plot by regression, was (1.06 +/- 0.11)x10(5)/M. Also, it was confirmed that the trans-diastereomer was more potent affinity with CCR4 than its cis-counterpart. The experimental results show that this reported method by CZE for the determination of the compound A and ML40 interactions is powerful, sensitive, and fast, requires less amounts of reagents, and further, it can be employed as one of the reliable screening methods to a series of lactam analogs in the drug discovery for allergic inflammation diseases.     

Membrane-dependent effects of a cytoplasmic helix on the structure and drug binding of the influenza virus M2 protein

The influenza A M2 protein forms a proton channel for virus infection and also mediates virus assembly and budding. The minimum protein length that encodes both functions contains the transmembrane (TM) domain (roughly residues 22-46) for the amantadine-sensitive proton-channel activity and an amphipathic cytoplasmic helix (roughly residues 45-62) for curvature induction and virus budding. However, structural studies involving the TM domain with or without the amphipathic helix differed on the drug-binding site. Here we use solid-state NMR spectroscopy to determine the amantadine binding site in the cytoplasmic-helix-containing M2(21-61). (13)C-(2)H distance measurements of (13)C-labeled protein and (2)H-labeled amantadine showed that in 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayers, the first equivalent of drug bound S31 inside the M2(21-61) pore, similar to the behavior of M2 transmembrane peptide (M2TM) in DMPC bilayers. The nonspecific surface site of D44 observed in M2TM is disfavored in the longer peptide. Thus, the pharmacologically relevant drug-binding site in the fully functional M2(21-61) is S31 in the TM pore. Interestingly, when M2(21-61) was reconstituted into a virus-mimetic membrane containing 30% cholesterol, no chemical shift perturbation was observed for pore-lining residues, whereas M2TM in the same membrane exhibited drug-induced chemical shift changes. Reduction of the cholesterol level and the use of unsaturated phospholipids shifted the conformational equilibrium of M2TM fully to the bound state but did not rescue drug binding to M2(21-61). These results suggest that the amphipathic helix, together with cholesterol, modulates the ability of the TM helix to bind amantadine. Thus, the M2 protein interacts with the lipid membrane and small-molecule inhibitors in a complex fashion, and a careful examination of the environmental dependence of the protein conformation is required to fully understand the structure-function relation of this protein.     

Cross sections for transitions between fine structure components of second group excited atoms induced by collisions with noble gas atoms

Cross sections of the transition ³ P ₁ ³ P ₀ for the atoms Zn, Cd, Hg upon collisions with inert gas atoms are calculated. It is shown that the transitions between fine structure components induced by nonadiabatic interaction are due to rotation of the molecule. A numerical estimation of the cross sections is performed.

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Zusammenfassung Es werden Wirkungsquerschnitte für den Übergang ³ P ₁ ³ P ₀ für die Atome Zn, Cd, Hg bei Stößen mit Edelgasatomen berechnet. Es wird gezeigt, daß die Übergänge zwischen Feinstrukturkomponenten, induziert durch nicht-adiabatische Wechselwirkung, durch Rotation des Moleküls bewirkt werden. Es wird eine numerische Abschätzung der Wirkungsquerschnitte durchgeführt.

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Résumé Calcul des sections efficaces pour la transition ³P₁ ³P₀ dans les atomes Zn, Cd, Hg par collision avec des atomes de gaz rare. On montre que les transitions entre les composantes de structure fine induites par interaction non adiabatique sont dues à la rotation de la molécule. Estimation numérique des sections efficaces.

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The authors are indebted to Dr. E. E. Nikitin for very valuable discussions.     

o-Nitrobenzoyl group as a new amino protecting group for peptide synthesis and the synthesis of some anthranilyl peptides

N (o-nitrobenzoyl)amino acids can be coupled with other amino acids using DCC and the resulting product on hydrogenation gives peptides, containing the anthranilyl group as —NH₂ end group. N (anthranilyl)amino acids or peptides can also be obtained by reaction of isatoic anhydride on amino acids or peptides. The anthranilyl end group is easily cleaved by metal (Cu⁺²) catalysed hydrolysis to give α-amino acid peptides and the insoluble copper(II) anthranilate.