某些环肽及其相应线型肽在不同溶剂中构象的CD谱研究

We used CD spectroscopy to study the conformations of three cyclic peptides (CP10E: cyclo[Glu(OBz1)-Pro-Gly-Glu(OBzl)-Gly]2, CP10K: cyclo[Lys(Z)-Pro-Gly-Lys(Z)-Gly]2, CP12K: cyclo[Phe-Lys(Z)-Pro-Gly-Lys(Z)-Gly]2 and their correspondent linear peptides (LP10E: Boc-[Glu(OBzl)-Pro-Gly-Glu(OBzl)-Gly]2-OPac, LP10K: Boc-[Lys(Z)-Pro-Lys(Z)-Pro]2-OMe, LP 12K: Bao- [-Lys(Z)-Pro-Gly-Lys(Z)-Gly]2- OMe) in three solvents of different polarity (chloroform, acetonitrile, 2,2,2-triliuroethanol), and it was found that all of linear and cyclicpeptides exists asγ-turn conformation in chloroform, however, in TFE＆ CH3CN solutions, the three linear peptides are inβ Ⅱ-turn conformations. CP10E isβI-turn conformation, CP10K ＆CP12K exists in more than one types of turn conformations. On the basis of our experiments, it was concluded: 1) In the presence of conformational constrained amino acids short linear peptides form obvious secondary structure; 2)The solvent polarity has influence on the peptide conformation and this influence on linear peptides is greater than that on cyclic peptides; 3)The backbone of cyclic peptide has constraint effect on its conformation and makes the secondary structure of cyclic peptide different from that of its relative linear peptide. This information might give some cules in the design of bioactive peptides with different receptor selectivity.     

Influence of turn (or fold) and local charge in fragmentation of the peptide analogue molecule CH3CO-Gly-NH2 following single-photon VUV (118.22 nm) ionization

The radical cationic reactivity of the peptide analogue molecule CH(3)CO-Gly-NH(2) is addressed both experimentally and theoretically. The radical cation intermediate of CH(3)CO-Gly-NH(2) is created by single-photon ionization of this molecule at 118.22 nm (~10.5 eV). The two most stable conformers (C(7) and C(5)) of this molecule exhibit different folds along the backbone: the C(7) conformer has a γ-turn structure, and the C(5) conformer has a β-strand structure. The experimental results show that the radical cation intermediate of CH(3)CO-Gly-NH(2) dissociates and generates a fragment-ion signal at 73 amu that is observed through TOFMS. Theoretical results show how the fragment-ion signal at 73 amu is generated by only one conformer of CH(3)CO-Gly-NH(2) (C(7)) and how local charge and specific hydrogen bonding in the molecule influence fragmentation of the radical cation intermediate of CH(3)CO-Gly-NH(2). The specific fold of the molecule controls fragmentation of this reactive radical cation intermediate. Whereas the radical cation of the C(7) conformer dissociates through a hydrogen-transfer mechanism followed by HNCO elimination, the radical cation of the C(5) conformer does not dissociate at all. CASSCF calculations show that positive charge in the radical cationic C(7) conformer is localized at the NH(2)CO moiety of the molecular ion. This site-specific localization of the positive charge enhances the acidity of the terminal NH(2) group, facilitating hydrogen transfer from the NH(2) to the COCH(3) end of the molecular ion. Positive charge in the C(5) conformer of the CH(3)CO-Gly-NH(2) radical cation is, however, localized at the COCH(3) end of the molecular ion, and this conformer does not have enough energy to surmount the energy barrier to dissociation on the ion potential energy surface. CASSCF results show that conformation-specific localization of charge in the CH(3)CO-Gly-NH(2) molecular ion occurs as a result of the different hydrogen-bonding interactions involved in the different molecular conformers.     

Effect of backbone flexibility on charge transfer rates in peptide nucleic acid duplexes

Charge transfer (CT) properties are compared between peptide nucleic acid structures with an aminoethylglycine backbone (aeg-PNA) and those with a γ-methylated backbone (γ-PNA). The common aeg-PNA is an achiral molecule with a flexible structure, whereas γ-PNA is a chiral molecule with a significantly more rigid structure than aeg-PNA. Electrochemical measurements show that the CT rate constant through an aeg-PNA bridging unit is twice the CT rate constant through a γ-PNA bridging unit. Theoretical calculations of PNA electronic properties, which are based on a molecular dynamics structural ensemble, reveal that the difference in the CT rate constant results from the difference in the extent of backbone fluctuations of aeg- and γ-PNA. In particular, fluctuations of the backbone affect the local electric field that broadens the energy levels of the PNA nucleobases. The greater flexibility of the aeg-PNA gives rise to more broadening, and a more frequent appearance of high-CT rate conformations than in γ-PNA.     

Structural and dynamic properties of water within the solvation layer around various conformations of the glycine-based polypeptide

Several conformations of the solvated glycine-based polypeptides were investigated using molecular dynamics simulations. Some properties of water in the neighboring space around these molecules were investigated. It was found that water forms a well-defined layer-the first solvation shell-around the peptide molecule, and thickness of this layer is independent of the peptide structure and is equal to approximately 0.28 nm. Within this layer, water molecules show marked orientations relative to a peptide surface. Using the two-particle contribution to entropy as a measure of structural ordering of water, we found that the first solvation shell contributes 95% or more to the total water ordering around the peptide molecule. In investigating the dynamic properties of water, diffusion coefficients and lifetime of the hydrogen bond, clear differences between solvation layer and the bulk water were observed. It was found that the translational diffusion coefficient, D(T), decreases by 30% or more compared to bulk water; also, the lifetime of the water-water hydrogen bond clearly increases. The rotational diffusion coefficient, however, decreases only slightly, no more than approximately 10%. These differences correspond to the slightly higher energy of the hydrogen bond, and to its slightly distorted geometry. Analyzing the translational dynamics of water in the vicinity of the peptide molecule, it was deduced that the structure of the first solvation shell becomes more rigid than the structure of the bulk water. Investigation of a "pure hydrophobic" form of the polypeptide shows that the structure and the properties of water within the solvation shell are predominantly determined by the hydrophobic effect. The specific interactions between water molecules and various charge groups of the peptide molecule modifies this effect only slightly.     

Salt-specific stability and denaturation of a short salt-bridge-forming alpha-helix

The structure of a single alanine-based Ace-AEAAAKEAAAKA-Nme peptide in explicit aqueous electrolyte solutions (NaCl, KCl, NaI, and KF) at large salt concentrations (3-4 M) is investigated using approximately 1 mus molecular dynamics (MD) computer simulations. The peptide displays 71% alpha-helical structure without salt and destabilizes with the addition of NaCl in agreement with experiments of a somewhat longer version. It is mainly stabilized by direct and indirect (" i + 4")EK salt bridges between the Lys and Glu side chains and a concomitant backbone shielding mechanism. NaI is found to be a stronger denaturant than NaCl, while the potassium salts hardly show influence. Investigation of the molecular structures reveals that consistent with recent experiments Na (+) has a much stronger affinity to side chain carboxylates and backbone carbonyls than K (+), thereby weakening salt bridges and secondary structure hydrogen bonds. At the same time, the large I (-) has a considerable affinity to the nonpolar alanine in line with recent observations of a large propensity of I (-) to adsorb to simple hydrophobes, and thereby "assists" Na (+) in its destabilizing action. In the denatured states of the peptide, novel long-lived (10-20 ns) "loop" configurations are observed in which single Na (+) ions and water molecules are hydrogen-bonded to multiple backbone carbonyls. In an attempt to analyze the denaturation behavior within the preferential interaction formalism, we find indeed that for the strongest denaturant, NaI, the protein is least hydrated. Additionally, a possible indication for protein denaturation might be a preferential solvation of the peptide backbone by the destabilizing cosolute (sodium). The mechanisms found in this work may be of general importance to understand salt effects on protein secondary structure stability.     

Ab initio calculations on blocked Pro-Ala dipeptides

The effect of the chirality of the amino acid at position i + 2 on a β-turn was investigated by a grid scan ab initio calculation on the Ac- -Pro- -Ala-NH₂ and Ac- -Pro- -Ala-NH₂ blocked dipeptides. Th6-31G basis set was used to estimate the effect of the alanyl side chain on the conformation of the peptide backbone in a blocked dipeptide as a simple, but complete model for a reverse turn. This study provides a quantum mechanical evaluation of the ability of the NH at the i + 3 residue to form the H-bond that closes the 10 membered ring which stabilizes the turn. The lowest energy of all 64 probed conformations of the -Ala containing peptide corresponded to a good type II β-turn with a hydrogen bond distance between the acetyl oxygen and the amide terminal hydrogen of 2.21 Å. A comparison with the nonblocked dipeptide ab initio study indicates that the presence of the end blocks enhances the propensity of the -Ala-containing dipeptide for a type II β-turn, but does not seem to enhance the propensity of the -Ala-containing dipeptide for a type I β-turn. The energies and geometric parameters for the lowest four optimized conformations identified by the grid scan search for each molecule have been calculated.     

新型十八核聚氧钼酸盐的合成与结构

合成了新化合物(NH4)6•[Ca2(H2O)6(CH3COO)2]•{Ca@[O52(OH)4(CH3COO)2]}•14H2O，并运用元素分析和单晶X衍射对其结构进行了表征.测定结果证实,该化合物由十八个钼氧八面体相互连接而成，呈现一种有趣的环状结构.在环的中心有一个Ca2＋离子，它通过与环上的四个酰氧配位而与环骨架相连.有十个钼原子呈正六价，而其余八个钼原子呈正五价，且有Mo－Mo键存在.环上还有配位相连的四个乙酸配体.在环的上下各有两个Ca2＋离子，它通过与该环和其它环上的氧原子配位而把环连成一维链状结构.晶体属三斜晶系，空间群P1，晶胞参数：a=1.055 2(2) nm， b=1.515 0(3) nm， c=1.544 9(3) nm， α=60.84(3)， β=88.00(3)， γ=71.21(3)°，V=2.019 4(7) nm3， R1=0.036 6（对可观察点）， wR2=0.083 3（对独立点）.     

Microsolvation of the sodium and iodide ions and their ion pair in acetonitrile clusters: a theoretical study

The structural and thermodynamic properties of Na+(CH3CN)n, I-(CH3CN)n, and NaI(CH3CN)n clusters have been investigated by means of room-temperature Monte Carlo simulations with model potentials developed to reproduce the properties of small clusters predicted by quantum chemistry. Ions are found to adopt an interior solvation shell structure, with a first solvation shell containing approximately 6 and approximately 8 acetonitrile molecules for large Na+(CH3CN)n and I-(CH3CN)n clusters, respectively. Structural features of Na+(CH3CN)n are found to be similar to those of Na+(H2O)n clusters, but those of I-(CH3CN)n contrast with those of I-(H2O)n, for which "surface" solvation structures were observed. The potential of mean force calculations demonstrates that the NaI ion pair is thermodynamically stable with respect to ground-state ionic dissociation in acetonitrile clusters. The properties of NaI(CH3CN)n clusters exhibit some similarities with NaI(H2O)n clusters, with the existence of contact ion pair and solvent-separated ion pair structures, but, in contrast to water clusters, both types of ion pairs adopt a well-defined interior ionic solvation shell structure in acetonitrile clusters. Whereas contact ion pair species are thermodynamically favored in small clusters, solvent-separated ion pairs tend to become thermodynamically more stable above a cluster size of approximately 26. Hence, ground-state charge separation appears to occur at larger cluster sizes for acetonitrile clusters than for water clusters. We propose that the lack of a large Na+(CH3CN)n product signal in NaI(CH3CN)n multiphoton ionization experiments could arise from extensive stabilization of the ground ionic state by the solvent and possible inhibition of the photoexcitation mechanism, which may be less pronounced for NaI(H2O)n clusters because of surface solvation structures. Alternatively, increased solvent evaporation resulting from larger excess energies upon photoexcitation or major solvent reorganization on the ionized state could account for the observed solvent-selectivity in NaI cluster multiphoton ionization.     

β-转角肽的溶液构象

主要报导TEM-1β-内酰胺酶的天然蛋白类抑制剂BLIP中一段多肽B1的溶液构象研究 结果.在磷酸盐缓冲溶液中,通过圆二色光谱、傅立叶红外光谱和核磁共振谱研究了B1的二 级结构特征.实验结果表明,B1在溶液中形成了β-转角结构,为在溶液中单独研究β-转 角结构形成与稳定性提供了良好的模板.β-转角在溶液中可以独立存在,表明β-转角在 蛋白质折叠过程中可能具有重要作用.     

红外光谱法研究温度变化对卵粘蛋白构象的影响

采用傅里叶变换红外(FTIR)光谱法和二维相关分析(2D Correlation analysis)技术研究了卵粘蛋白(Ovomucin)的构象转变与温度之间的关系. 结果表明, 当温度为55~65℃时, 卵粘蛋白的红外谱峰的位置和强度发生较大改变. 二维相关分析表明, 在升温过程中, 与肽链相比卵粘蛋白分子中的糖链对温度变化更为敏感, 且优先发生构象改变, 糖链分子的存在利于维持卵粘蛋白构象的热稳定性. 在25~95℃升温过程中, 卵粘蛋白分子二级结构的变化次序依次为α-螺旋、 β-折叠、 β-转角和无规卷曲. 由温度变化引起的卵粘蛋白分子结构动态变化的微观信息, 为揭示变温微扰引起的蛋白构象变化机理提供了初步的理论依据.     

A Tricyclic Template Derived from (2S,4R)-4-Hydroxyproline for the Synthesis of Protein Loop Mimetics

A tricyclic diketopiperazine, formally derived by coupling (2S,4S)-4-aminoproline (Pro(NH₂)) and (2S,4R)-4-(carboxymethyl)proline (Pro(CH₂COOH)), is synthesized starting from readily available (2S,4R)-4-hydroxyproline. The resulting tricyclic template has carboxy and amino groups to which a peptide chain may be attached. The Fmoc-protected template 5 is incorporated into the cyclic molecule cyclo(-Ala¹-Asn²-Pro³-Asn⁴-Ala⁵-) ( 6 ) where Pro(NH₂)⁷ = Pro(CH₂COOH)⁸ represents the template, using solid-phase peptide synthesis with cyclization in solution. The molecule is shown by NMR and dynamic simulated annealing methods to adopt a preferred conformation in aqueous solution, which includes an extended backbone at the residues Asn²-Pro³-Asn⁴, and a type-Iβ-turn at . These studies show that this novel template may be used in the synthesis of cyclic peptide and protein mimetics having defined secondary structure in aqueous environments.     

One-Dimensional Hydrogen-bonded Double Chain Composed of a Copper(II) Complex with Chelidamic Acid

1INTRODUCTION Chelidamic acid(2,6-dicarboxy-4-hydroxypyri-dine),an emblematical polydentate ligand,has been of great attraction due to its usage in many areas of science,such as coordinate chemistry,biochemis-try,organic chemistry,medical chemistry and even in HIV investigation[1].More and more metal com-plexes containing chelidamic acid ligands have been reported,which play a significant role in de-signing the molecules and extending chemistry of chelidamic acid[2].In our previous paper…     

Design of Peptides with α,β-Dehydro Residues: Synthesis,Crystal Structure and Molecular Conformation of a Peptide N-Boc-Phe-ΔPhe-Ile-OCH<Subscript>3</Subscript>

To develop a complete set of design rules with α,β-dehydro residues, a tripeptide N-Boc-Phe-ΔPhe-Ile-OCH₃ was synthesized. The synthesis was carried out in solution phase using azlactone procedure. The three-dimensional structure of the peptide was determined by X-ray diffraction method and refined to an R-factor of 0.085. The structure contains three peptide molecules in the asymmetric unit. In all the three crystallographically independent molecules ΔPhe residue adopts one of the three conformations that have been reported for a ΔPhe residue. The overall conformations of three peptide molecules in the asymmetric unit are not similar. Two out of three crystallographically independent molecules adopt type II β-turn conformations whereas the third molecule is found having the characteristic S-shaped conformation in which the values of dihedral angles φ, ψ have opposite signs alternately. One of these two types of conformations has been observed when a ΔPhe is introduced at (i+2) position of a tetrapeptide. The β-turn conformation is stabilized by a 4→1 hydrogen bond where the hydrophobic side chains of residues at (i+1) and (i+3) positions stabilized the unfolded conformation with van der Waals interactions. The three independent molecules are locked together by three hydrogen bonds between molecules A and B and two hydrogen bonds between molecules B and C.     

Structure of a cyclic peptide with a catalytic triad, determined by computer simulation and NMR spectroscopy

Summary We report the design of a cyclic, eight-residue peptide that possesses the catalytic triad residues of the serine proteases. A manually built model has been relaxed by 0.3 ns of molecular dynamics simulation at room temperature, during which no major changes occurred in the peptide. The molecule has been synthesised and purified. Two-dimensional NMR spectroscopy provided 35 distance and 7 torsion angle constraints, which were used to determine the three-dimensional structure. The experimental conformation agrees with the predicted one at the -turn, but deviates in the arrangement of the disulphide bridge that closes the backbone to a ring. A 1.2 ns simulation at 600 K provided extended sampling of conformation space. The disulphide bridge reoriented into the experimental arrangement, producing a minimum backbone rmsd from the experimental conformation of 0.8 . At a later stage in the simulation, a transition at Ser³ produced more pronounced high-temperature behaviour. The peptide hydrolyses p-nitrophenyl acetate about nine times faster than free histidine.     

β-Loop, γ-loop,and helical peptide conformations in cyclopeptides containing a steroidal pseudo-amino acid

The steroidal pseudo-amino acids 3ã-amino-5β-cholan-24-oic acid ( 2a ), 12ã-acetoxy-3ã-ammonia-5β-cholan-24-oic acid ( 2b ), and 7ã,12ã-diacetoxy-3ã-amino-5β-cholan-24-oic acid ( 2c ) are used as rigid spacers in the backbone of the cyclic peptides cyclo(– 2a –Phe-Phe–)₂ ( 1a ), cyclo(– 2b –Phe-Phe–)₂ ( 1b ), and cyclo(–2c-Phe-Phe–)₂ ( 1c ). A homogeneous β-loop conformation is found in the peptide chains of 1a and 1b , while 1c exists as a mixture of ã-helical and γ-loop conformations. The structure and homogeneity of the conformations are established by several NMR techniques and are supported by molecular-dynamics calculations. The peptide conformations depend on the distance and attraction of the two large and lipophilic steroidal parts of the cyclic molecules.     

A molecular dynamics study of the pentacyclo-undecane cage amino acid tripeptide

In this paper, we report on the conformational profile of the pentacyclo-undecane (PCU) cage tripeptide carried out by molecular dynamics (MD) simulation using water as an explicit solvent. The MD solution phase studies carried on the model peptide analogues (A)=Ac–Ala–Ala–Ala–NHMe; (B)=Ac–Cage–Cage–Cage–NHMe; (C)=Ac–Ala–Cage–Ala–NHMe and (D)=Ac–Ala–Pro–Ala–NHMe, are used as a complimentary technique to the corresponding gas phase simulated annealing (SA) study previously carried out in our laboratory. No significant structural changes were observed over the MD trajectories. However, the results reported here provide further evidence that the (PCU) cage amino acid exhibits C_7eq, C_7aq, _R and _L conformations, and the theoretical results suggest that the PCU cage amino acid is a strong β-turn inducer. These results support the prediction that when the PCU cage residues are in the (i) and (i+2) positions, the β-turn can be extended in either direction to form anti-parallel β-pleated sheets, thereby forming the basis of the mechanism for the folding back of the chain in a cross-β-turn structure.     

Syntheses, Spectra, and Structures of (Diphosphine)platinum(II) Carbonate Complexes

A variety of (diphosphine)platinum(II) carbonate complexes, (LL)Pt(CO(3)), are readily prepared from the corresponding (diphosphine)platinum dichlorides by treatment with silver carbonate in dichoromethane solution provided that water is present. This reaction also permits facile preparation of analogous (13)C-labeled complexes. The carbonate ligands in these complexes have been characterized by IR and (13)C NMR spectroscopy. Alternative preparative routes involve conversion of the precursor dichlorides to the corresponding dialkoxides or diphenoxides, followed by treatment with water and carbon dioxide. Various reaction intermediates have been spectroscopically observed in the latter syntheses. Two crystalline modifications of (Ph(2)PCH(2)CH(2)CH(2)PPh(2))Pt(CO(3)), one with and one without a dichloromethane of solvation, have been studied by single-crystal X-ray diffraction. Crystal data for PtP(2)O(3)C(28)H(26): P2(1)/c, Z = 4, T = 200 K, a = 10.362(8) ?, b = 14.743(6) ?, c = 19.183(10) ?, beta = 122.69(6) degrees. Crystal data for PtP(2)O(3)C(28)H(26).CH(2)Cl(2): P2(1)/c, Z = 4, T approximately 298 K, a = 11.744(2) ?, b = 15.526(3) ?, c = 15.866(3) ?, beta = 101.58(1) degrees.     

含有D型氨基酸的新型毒肽——芋螺马芬在pH 5的溶液结构

Conomarphin, a novel conopeptide containing D-amino acid, was identified from the venom of Conus marmoreus and classified into M-superfamily of conotoxin. In this article, we reported the 3D structure of conomarphin at pH 5 determined using 2D 1H NMR method in aqueous solution. Twenty converged structures of this peptide were obtained based on 205 distance constraints, 8 dihedral angle constraints, and 2 hydrogen bond constraints. The root mean square deviation (RMSD) values of the backbone atoms were (0.074依0.029) nm. The refined structure of conomarphin at pH 5 contained a short 310-helix at C-terminal of the peptide. It was also characterized by a loose loop centered at Ala6. Comparison of structural and electrostatic potential between conomarphin at pH 3 and pH 5 were presented. Although the solution structure of conomarphin at pH 5 shared part of the same secondary structure element with the structure of conomarphin at pH 3, it adopted a distinctive backbone conformation with the overall molecule resembling a“flexcual arm”when viewed fromthe front. Structural differences imply that this conopeptide is rather pH sensitive and its bioactivity in vivo might be related to the acidity.     

ESR studies of γ-irradiated histone octamer and the histone H3

ESR spectrum of neat histone H3 γ-irradiated and observed at 77 K with low microwave power and modulation amplitude showed multiple resolved structure depicting nonequivalent interaction of the unpaired electron located at amido-carbonyl radical anion [– )NH–] of the peptide backbone with adjacent –NH– group and the β-proton of –CH group. The predominance of amido-carbonyl radical anion is in good accord with the expected partition of secondary electrons amongst the various electrophilic groups including peptide carbonyl and aromatic acid residues. Following a gradual rise of annealing temperature to room temperature, a double splitting spectrum from the well known -carbon amido radical was evolved.     

Circular dichroism study of the carbohydrate-modified opioid peptides

The conformational preferences of enkephalins and the related glycoconjugates in which free or protected carbohydrate moieties were linked to the opioid peptides through an ether, ester or amide bond were investigated by circular dichroism spectroscopy in water, trifluoroethanol and water-trifluoroethanol mixtures. The analysis of the spectra revealed that the conformation of the enkephalin molecule is very sensitive to slight changes in the peptide structure around the C-terminal region. It was found that the type II beta-turn structures are populated in N-terminal tetrapeptide enkephalin fragment, while leucine-enkephalin amide feature a type I (III) beta-turn structure in solution. Incorporation of the sugar moiety into opioid peptide compound did not significantly influence the overall conformation of the peptide backbone, although minor intensity changes may reflect shifts in the population of the different turn systems. These small structural alterations can be responsible for the receptor-subtype selectivity of the various carbohydrate-modified enkephalin analogs.