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41.
To determine which of a variety of inorganic and organic selenium compounds could best stimulate glutathione peroxidase, human lymphocytes were cultured with a number of selenium sources. The phytohemagglutinin-transformed lymphocytes were cultured in the presence of75Se bound to serum proteins (25% v/v) or 10?7 M concentrations of [75Se]-selenite, [75Se]-selenate, [75Se]-selenocystine, and [75Se]-selenomethionine. Organic forms of selenium were taken up in preference to inorganic forms. Control cultures, from which exogenous selenium had been omitted, showed a decreased level of glutathione peroxidase activity at the end of a 4 d culture period. Of the Se sources tested, [75Se]-selenocystine and [75Se]-labeled fetal calf serum proteins increased enzyme activity significantly, 79 and 47%, respectively, but selenite increased activity only by 7%. These results indicate that selenium from the two organic sources is most readily available for glutathione peroxidase synthesis. 相似文献
42.
Three crystalline polymorphs of the helical decapeptide, Boc-Aib-Ala-Leu-Ala-Leu-Aib-Leu-Ala-Leu-Aib-OMe, have been obtained. Antiparallel helix aggregation is observed in crystals grown from methanol (A), while completely parallel packing is observed in crystals from isopropanol (B) or an ethylene glycol-ethanol mixture (C). Crystals B and C are very similar in molecular conformation and packing. The packing motifs in crystals A and B consist of rows of parallel molecules, with an almost identical arrangement in both crystals. In crystal A, adjacent rows assemble with the helix axes pointed in opposite directions, whereas in crystal B all rows assemble with helix axes pointed in the same direction. Electrostatic interactions between helix dipoles do not appear to be a major determinant of packing modes. The structures also do not provide a ready rationalization of packing preferences in terms of side-chain interactions or solvation. The alpha-helix of the peptide in crystal A has seven 5----1 hydrogen bonds; the helix in crystal B is a mixed 3(10)/alpha-helix. The crystal parameters are as follows. Crystal A: C51H92N10O13.CH3OH, space group P2(1) with a = 10.498 (1) A, b = 18.189 (3) A, c = 16.475 (3) A, beta = 99.28 (1) degree, Z = 2, R = 9.6% for 1860 data. Crystal B: C51H92N10O13.C3H7OH, space group P2(1) with a = 10.534 (1) A, b = 28.571 (4) A, c = 11.055 (2) A, beta = 95.74 (1) degree, Z = 2, R = 6.5% for 3251 data. Crystal C: C51H92N10O13.C2H5OH, space group P2(1), with a = 10.450 (1) A, b = 28.442 (5) A, c = 11.020 (2) A, beta = 95.44(1) degree, Z = 2, R = 14.8% (isotropic) for 1948 data. 相似文献
43.
Chlamydocin, Iabu-L -Phe-D -Pro-L X, is a naturally occurring cyclic tetrapeptide that exhibits high cytostatic activity. The conformation of the peptide ring, as well as the stereo configuration in the vicinity of the epoxide ring, have been established by a single-crystal X-ray study of dihydrochlamydocin: C28H40N4O6·H2O. It crystallizes in the monoclinic space group P21 with a = 12.616(6) Å, b = 12.355(6) Å, c = 9.442(5) Å, and β = 99.5(1)°. The structure was solved by the symbolic addition procedure for phase determination followed by the tangent formula method of phase refinement. This structure represents the first cyclic tetrapeptide in which all four peptide units have been found in the trans conformation; however, each peptide unit is significantly nonplanar with ω angles deviating by 14–24° from the ideal value of 180°. This molecule contains two intramolecular 3 → 1 hydrogen bonds and experimentally determined parameters for these seven-membered turns are presented. 相似文献
44.
Experiments with various labelled cinnamic acid derivatives establish, in conjunction with previous work, that the incorporation of phenylalanine into the 3a-aryl octahydroindole ring system of the mesembrine alkaloids occurs via the intermediacy of cinnamic acid and 4′-hydroxycinnamic acid. The major pathway to the 3′,4′-di-oxyaryl substituted alkaloids proceeds via 4′-hydroxydihydrocinnamic acid (4′-phloretic acid), and 3′4′-dioxy-genated cinnamic acids are not involved as intermediates on this major pathway. In accord with this latter finding, the 3′-aryl oxygen substituent is introduced at a late state in the biosynthesis as evidenced by the bioconversion in S. strictum of sceletenone to mesembrenol and other related alkaloids. The late stages in the biosynthesis of the alkaloids are shown to involve the sequence: sceletenone, 4′-O-demethylmesembrenone, mesembrenone. Mesembrenone is converted to mesembrine, mesembrenol and mesembranol. 相似文献
45.
The incporation of beta-amino acid residues into the strand segments of designed beta-hairpin leads to the formation of polar sheets, since in the case of beta-peptide strands, all adjacent carbonyl groups point in one direction and the amide groups orient in the opposite direction. The conformational analysis of two designed peptide hairpins composed of alpha/beta-hybrid segments are described: Boc-Leu-betaPhe-Val-(D)-Pro-Gly-Leu-betaPhe-Val-OMe (1) and Boc-betaLeu-Phe-betaVal-D-Pro-Gly-betaLeu-Phe-betaVal-OMe (2). A 500-MHz 1H-NMR (nuclear magnetic resonance) analysis in methanol supports a significant population of hairpin conformations in both peptides. Diagnostic nuclear Overhauser effects (NOEs) are observed in both cases. X-ray diffraction studies on single crystals of peptide 1 reveal a beta-hairpin conformation in both the molecules, which constitute the crystallographic asymmetric unit. Three cross-strand hydrogen bonds and a nucleating type II' beta-turn at the D-Pro-Gly segment are observed in the two independent molecules. In peptide 1, the betaPhe residues at positions 2 and 7 occur at the nonhydrogen-bonding position, with the benzyl side chains pointing on opposite faces of the beta-sheet. The observed aromatic centroid-to-centroid distances are 8.92 A (molecule A) and 8.94 A (molecule B). In peptide 2, the aromatic rings must occupy facing positions in antiparallel strands, in the NMR-derived structure.Peptide 1 yields a normal "hairpin-like" CD spectrum in methanol with a minimum at 224 nm. The CD spectrum of peptide 2 reveals a negative band at 234 nm and a positive band at 221 nm, suggestive of an exciton split doublet. Modeling of the facing Phe side chains at the hydrogen-bonding position of a canonical beta-hairpin suggests that interring separation is approximately 4.78 A for the gauche+ gauche- (g+ g-) rotamer. A previously reported peptide beta-hairpin composed of only alpha-amino acids, Boc-Leu-Phe-Val-D-Pro-Gly-Leu-Phe-Val-OMe also exhibited an anomalous far-UV (ultraviolet) CD (circular dichroism) spectrum, which was interpreted in terms of interactions between facing aromatic chromophores, Phe 2 and Phe 7 (C. Zhao, P. L. Polavarapu, C. Das, and P. Balaram, Journal of the American Chemical Society, 2000, Vol 122, pp. 8228-8231). 相似文献
46.
Nishiyama Y Bhatia G Bangale Y Planque S Mitsuda Y Taguchi H Karle S Paul S 《The Journal of biological chemistry》2004,279(9):7877-7883
We report the selective inactivation of proteolytic antibodies (Abs) to an autoantigen, the neuropeptide vasoactive intestinal peptide (VIP), by a covalently reactive analog (CRA) of VIP containing an electrophilic phosphonate diester at the Lys(20) residue. The VIP-CRA was bound irreversibly by a monoclonal Ab that catalyzes the hydrolysis of VIP. The reaction with the VIP-CRA proceeded more rapidly than with a hapten CRA devoid of the VIP sequence. The covalent binding occurred preferentially at the light chain subunit of the Ab. Covalent VIP-CRA binding was inhibited by VIP devoid of the phosphonate diester group. These results indicate the importance of noncovalent VIP recognition in guiding Ab nucleophilic attack on the phosphonate group. Consistent with the covalent binding data, the VIP-CRA inhibited catalysis by the recombinant light chain of this Ab with potency greater than the hapten-CRA. Catalytic hydrolysis of VIP by a polyclonal VIPase autoantibody preparation that cleaves multiple peptide bonds located between residues 7 and 22 essentially was inhibited completely by the VIP-CRA, suggesting that the electrophilic phosphonate at Lys(20) enjoys sufficient conformational freedom to react covalently with Abs that cleave different peptide bonds in VIP. These results suggest a novel route to antigen-specific covalent targeting of pathogenic Abs. 相似文献
47.
Self-assembly patterns as a function of the central core insert in the retro bis-peptide dicarboxylic acids HO? Aib? X? Aib? OH, containing oxalyl (-CO? CO? 1), fumaryl (? O? CH?CH ? CO ? ;2), and adipoyl [? CO? (CH2)4 ? CO? 3], have been characterized by single crystal x-ray diffraction analyses. Extensive hydrogen bonding occurs in each crystal but there are no OH…O bonds between acid groups. Only two types of hydrogen bonds occur in all the crystals:NH…O (acid terminal),2.84-2.98 Åand OH (acidterminal)…O (corecarbonyl),2.55–2.67 Å (exceptfor an additional intramolecular C5 type bond in the oxalyl moiety in 1). The self-assembly patterns are a β-network in1, separate layer assemblies (β-networks) for two independent molecules in 2 that combine into a three-dimensional γnetwork, and separate ribbon assembles (αnetworks) for two independent molecules in 3 that combine into an extended β-network sheet withhydrophobic faces. © 1995 John Wiley & Sons, Inc. 相似文献
48.
Facile transition between 3(10)- and alpha-helix: structures of 8-, 9-, and 10-residue peptides containing the -(Leu-Aib-Ala)2-Phe-Aib- fragment. 总被引:1,自引:0,他引:1
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I. L. Karle J. L. Flippen-Anderson R. Gurunath P. Balaram 《Protein science : a publication of the Protein Society》1994,3(9):1547-1555
A structural transition from a 3(10)-helix to an alpha-helix has been characterized at high resolution for an octapeptide segment located in 3 different sequences. Three synthetic peptides, decapeptide (A) Boc-Aib-Trp-(Leu-Aib-Ala)2-Phe-Aib-OMe, nonapeptide (B) Boc-Trp-(Leu-Aib-Ala)2-Phe-Aib-OMe, and octapeptide (C) Boc-(Leu-Aib-Ala)2-Phe-Aib-OMe, are completely helical in their respective crystals. At 0.9 A resolution, R factors for A, B, and C are 8.3%, 5.4%, and 7.3%, respectively. The octapeptide and nonapeptide form ideal 3(10)-helices with average torsional angles phi(N-C alpha) and psi(C alpha-C') of -57 degrees, -26 degrees C and -60 degrees, -27 degrees for B. The 10-residue peptide (A) begins as a 3(10)-helix and abruptly changes to an alpha-helix at carbonyl O(3), which is the acceptor for both a 4-->1 hydrogen bond with N(6)H and a 5-->1 hydrogen with N(7)H, even though the last 8 residues have the same sequence in all 3 peptides. The average phi, psi angles in the decapeptide are -58 degrees, -28 degrees for residues 1-3 and -63 degrees, -41 degrees for residues 4-10. The packing of helices in the crystals does not provide any obvious reason for the transition in helix type. Fourier transform infrared studies in the solid state also provide evidence for a 3(10)- to alpha-helix transition with the amide I band appearing at 1,656-1,657 cm-1 in the 9- and 10-residue peptides, whereas in shorter sequences the band is observed at 1,667 cm-1. 相似文献
49.
Carl I. Webster Christine J. Bryson Edward A. Cloake Tim D. Jones Mark J. Austin Anette C. Karle 《MABS-AUSTIN》2016,8(2):253-263
The immunogenicity of clinically administered antibodies has clinical implications for the patients receiving them, ranging from mild consequences, such as increased clearance of the drug from the circulation, to life-threatening effects. The emergence of methods to engineer variable regions resulting in the generation of humanised and fully human antibodies as therapeutics has reduced the potential for adverse immunogenicity. However, due to differences in sequence referred to as allotypic variation, antibody constant regions are not homogeneous within the human population, even within sub-classes of the same immunoglobulin isotype. For therapeutically administered antibodies, the potential exists for an immune response from the patient to the antibody if the allotype of patient and antibody do not match. Allotypic distribution in the human population varies within and across ethnic groups making the choice of allotype for a therapeutic antibody difficult. This study investigated the potential of human IgG1 allotypes to stimulate responses in human CD4+ T cells from donors matched for homologous and heterologous IgG1 allotypes. Allotypic variants of the therapeutic monoclonal antibody trastuzumab were administered to genetically defined allotypic matched and mismatched donor T cells. No significant responses were observed in the mismatched T cells. To investigate the lack of T-cell responses in relation to mismatched allotypes, HLA-DR agretopes were identified via MHC associated peptide proteomics (MAPPs). As expected, many HLA-DR restricted peptides were presented. However, there were no peptides presented from the sequence regions containing the allotypic variations. Taken together, the results from the T-cell assay and MAPPs assay indicate that the allotypic differences in human IgG1 do not represent a significant risk for induction of immunogenicity. 相似文献
50.
The forms of Se in the Se-dependent enzyme formate dehydrogenase is known to be selenocysteine, but the way this amino acid enters the polypeptide chain has not been established. Through the use of a cysteine-requiring mutant ofEscherichia coli K-12 that could also grow in the presence of glutathione, we were able to study the effect of selenite, selenide, andl-selenocysteine, each at a concentration of 0.1 μM, on the synthesis of formate dehydrogenase. The three forms of Se served equally well for inducing formate dehydrogenase activity, measured by dichlorophenol-indophenol reduction mediated by phenazine methosulfate. It is known that selenite can be reduced to selenide by the action of glutathione reductase, present inE. coli, and that selenocysteine is converted to elemental Se by the action of selenocysteine lyase, also present in the mutant. Elemental Se is then reduced nonenzymatically to hydrogen selenide. The conversion of both selenite and selenocysteine to selenide and the ability of each form of Se to induce the synthesis of equal levels of formate dehydrogenase suggest that the incorporation of Se into formate dehydrogenase is accomplished by a posttranslational mechanism. 相似文献