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. 相似文献
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. 相似文献
Two molecules of the steroid lithocholic acid and two dipeptides (Phe-Phe) make up the macrocycle 1 , in which the two steroidal surfaces approach each other so that the peptide parts fold into β(I) turns. Thus, the structure of a cyclic steroid–peptide compound was determined in the solid state for the first time. The structure of 1 is stabilized in the crystal through intra- and intermolecular hydrogen bonds as well as through π stacking of the side-chain phenyl rings of Phe(i+1). 相似文献
A series of β,γ‐unsaturated ketones were isomerized to their corresponding α,β‐unsaturated ketones by the introduction of DABCO in iPrOH at room temperature. The endo‐cyclic double bond (β,γ‐position) on ketone was rearranged to exo‐cyclic double bond (α,β‐position) under the reaction conditions. 相似文献
Irradiation (λ >300 nm) of Hantzsch 1,4-dihydropyridine with aromatic α,β-epoxyketones in acetonitrile selectively breaks the Cα---O bond of the epoxides giving the corresponding β-hydroxyketones in excellent yields. 相似文献
The closed-shell interactions in oligo- and polyalanines are studied by the quantum theory of atoms in molecules (QTAIM) using electron densities derived from the B3LYP/6-31+G** ground-state electronic wave-functions. The QTAIM enabled us to identify a large number of the intraturn closed-shell stabilizing interactions in the β-turns, which were presented by several conformers of the tetrapeptide model compound. We found that only β-turn type IVa exhibits a 10-member pseudocycle. The intrachain H-bonds between the adjacent N–H and CO groups in the antiparallel β-sheet conformation of polyalanine have not been found. At the same time, these interactions do exist in the parallel conformation and are even stronger than the interchain N–H…O bonds. A weak interaction between the CO group at the position i and the side-chain C–H group at the position i + 3 was detected in the -helical conformation of polyalanine. 相似文献
A series of model dipeptides containing some novel axially chiral α,β-didehydroamino acids at the (i+1) position has been synthesised by reaction of the corresponding 4-(4-alkylcyclohexylidene)-2-phenyl-1,3-oxazol-5(4H)-one with (S)-phenylalanine cyclohexylamide. The conformations of two dipeptides in the crystal state have been studied by X-ray diffraction crystallographic analysis. The backbone torsion angles suggest that both peptides adopt similar type-II′ β-turn conformations. NMR spectroscopy has revealed that relatively rigid β-turn structures also persist in solution and that the absolute configurations of the axially chiral α,β-didehydroamino acids do not significantly influence the conformation of the peptide chain. Both heterochiral and homochiral dipeptides are found to accommodate the same βII′-turn conformation. Axially chiral α,β-didehydroamino acids (Ra)- and (Sa)-4-methyl-, 4-phenyl- and (4-tert-butylcyclohexylidene)glycine can be considered as elongated structural analogues of alanine, phenylglycine and tert-leucine of R and S configuration since, in these chiral α,β-didehydroamino acids, the methyl, phenyl and tert-butyl groups are located about 4.3 Å away from the peptide backbone in which they are incorporated. 相似文献
IR studies were preformed to determine possible transition metal ion binding sites of penicillin. the observed changes in spectral position and shape of characteristic IR bands of cloxacillin in the presence of transition metal ions (both in solutions and in the solid state) indicate formation of M–L complexes with engagement of –COO− and/or –CONH– functional groups. The small shift of νC=O towards higher frequencies rules out direct M–L interaction via β-lactam carbonyl. PM3 calculations on simple model compounds (substituted formamide, cyclic ketones, lactams and substituted monocyclic β-lactams) have been performed. All structures were fully optimized and the calculated bond lengths, angles, heats of formation and C=O stretching frequencies were discussed to determine the β-lactam binding sites and to explain its susceptibility towards nucleophilic attack (hydrolysis in vitro) and biological activity. The relative changes of calculated values were critically compared with available experimental data and same correlation between structural parameters and in vivo activity was shown. 相似文献
In order to study the influence of the side-chain orientation on the peptide backbone conformation we have synthesised the model dipeptides t-BuCO-l-Pro-(1S,2R)-c6Phe-NHMe and t-BuCO-l-Pro-(1R,2S)-c6Phe-NHMe, incorporating each enantiomer of the trans cyclohexane analogue of phenylalanine (trans-1-amino-2-phenylcyclohexanecarboxylic acid). The orientation of the aromatic side-chain determines the β-turn type accommodated by these peptides to the point that the (1S,2R)-c6Phe derivative retains the type I β-turn in the crystalline state, in contrast to the behaviour exhibited by the natural counterpart t-BuCO-l-Pro-l-Phe-NHMe. 相似文献
The conformational analysis of naturally occurring cytostatic cyclic heptapeptides axinastatin 2, 3, and 4 was carried out by two-dimensional NMR spectroscopy in combination with distance-geometry (DG) and molecular-dynamics (MD) calculations in explicit solvents. The synthesized secondary metabolites were examined in (D6)DMSO. Axinastatin 2 was also investigated in CD3OH. In all structures, Pro2 is in the i + 1 position of a βI turn and Pro6 occupies the i + 2 position of a βVIa turn about the cis amide bond between residue 5 and Pro6. In all peptides, a bifurcated H-bond occurs between residue 4 CO and the amide protons of residue 1 and 7. For axinastatin 2 and 3, an Asn Ig turn was found about Asn1 and Pro2. We compared these structures with conformations of cyclic heptapeptides obtained by X-ray and NMR studies. A β-bulge motif with two β turns and one bifurcated H-bond is found as the dominating backbone conformation of cyclic all-L-heptapeptides. Axinastatin 2, 3, and 4 can be characterized by six trans and one cis amide bond resulting in a β/βVI(a)-turn motif, a conformation found for many cyclic heptapeptides. Detailed biological tests of the synthetic compounds in different human cancer cell lines indicates these axinastatins to be inactive or of low activity. 相似文献
The conformational behavior of POE-bound model peptides Boc-(L -Ala)2-X-Y-(L -Ala)2-NHPOE (X – Y = L -Pro-Gly ( I ), Gly-L -Ile ( II ); NHPOE = aminopoly(oxyethylene)) as well as of the repetitive hexapeptide of elastin, Boc-L -Val-L -Ala-L -Pro-Gly-L -Val-Gly-A-NHPOE-M ( III ) (A = photosensitive 3-nitro-4-(bromomethyl)benzoyl group; NHPOE-M = aminopoly(oxyethylane) monomethyl ether) has been studied by means of 1H-NMR and CD spectroscopy. Compounds I and III form a β-turn with Pro and Gly in positions i + 1 and i + 2, respectively, while an aggregated state for II , has been identified. The results are in good agreement with published prediction codes giving experimental evidence for the dominance of short-range interactions to establish secondary structure in solution. 相似文献
β-Amino-α-phenyl-α-ferrocenylethanol, FcC(OH)(Ph)CH2NH2 was prepared by the reduction of cyanohydrin trimethylsilyl ether of benzoylferrocene with lithium aluminum hydride. This new compound was characterized by elemental analysis, IR and 1H NMR spectroscopy. The structure was also confirmed by a single crystal X-ray study. The compound crystallizes in monoclinic P21/c space group with unit cell dimensions: a = 12.5906(17), b = 5.9636(8), c = 19.8320(3) Å, β = 102.047(2)∘, V = 1456.3(3) Å3, Z = 4. The structure exhibits intra- and inter-molecular hydrogen bonding of the type N—H⋅ < eqid1 > ⋅O and O—H⋅ < eqid2 > ⋅N, respectively. The pattern of the inter-molecular hydrogen bonding interaction contains a 10-atom ring with two donors and two acceptors, showing a dimeric crystal packing. 相似文献
The crystal structure of methyl α‐d ‐mannopyranosyl‐(1→3)‐2‐O‐acetyl‐β‐d ‐mannopyranoside monohydrate, C15H26O12·H2O, ( II ), has been determined and the structural parameters for its constituent α‐d ‐mannopyranosyl residue compared with those for methyl α‐d ‐mannopyranoside. Mono‐O‐acetylation appears to promote the crystallization of ( II ), inferred from the difficulty in crystallizing methyl α‐d ‐mannopyranosyl‐(1→3)‐β‐d ‐mannopyranoside despite repeated attempts. The conformational properties of the O‐acetyl side chain in ( II ) are similar to those observed in recent studies of peracetylated mannose‐containing oligosaccharides, having a preferred geometry in which the C2—H2 bond eclipses the C=O bond of the acetyl group. The C2—O2 bond in ( II ) elongates by ~0.02 Å upon O‐acetylation. The phi (?) and psi (ψ) torsion angles that dictate the conformation of the internal O‐glycosidic linkage in ( II ) are similar to those determined recently in aqueous solution by NMR spectroscopy for unacetylated ( II ) using the statistical program MA′AT, with a greater disparity found for ψ (Δ = ~16°) than for ? (Δ = ~6°). 相似文献
The β-sheet is one of the common protein secondary structures, and the aberrant aggregation of β-sheets is implicated in various neurodegenerative diseases. Cross-strand interactions are an important determinant of β-sheet stability. Accordingly, both diagonal and lateral cross-strand interactions have been studied. Surprisingly, diagonal cross-strand ion-pairing interactions have yet to be investigated. Herein, we present a systematic study on the effects of charged amino acid side-chain length on a diagonal ion-pairing interaction between carboxylate- and ammonium-containing residues in a β-hairpin. To this end, 2D-NMR was used to investigate the conformation of the peptides. The fraction folded population and the folding free energy were derived from the chemical shift data. The fraction folded population for these peptides with potential diagonal ion pairs was mostly lower compared to the corresponding peptide with a potential lateral ion pair. The diagonal ion-pairing interaction energy was derived using double mutant cycle analysis. The Asp2-Dab9 (Asp: one methylene; Dab: two methylenes) interaction was the most stabilizing (−0.79 ± 0.14 kcal/mol), most likely representing an optimal balance between the entropic penalty to enable the ion-pairing interaction and the number of side-chain conformations that can accommodate the interaction. These results should be useful for designing β-sheet containing molecular entities for various applications. 相似文献
Maintaining specific conformations of peptide ligands is crucial for improving the efficacy of biological interactions. Here, a one‐pot polymerization strategy for stabilizing the α‐helical conformation of peptides while simultaneously constructing multimeric ligands is presented. The new method, termed stapling polymerization, uses radical polymerization between acryloylated peptide side chains and vinylic monomers. Studies with model peptides indicate that i, i+7 crosslinking is effective for the helix stabilization, whereas i, i+4 crosslinking is not. The stapling polymerization results in the formation of peptide–polyacrylamide conjugates that include ≈3–16 peptides in a single conjugate. This stapling polymerization provides a simple but powerful methodology to fabricate multimeric α‐helices that can further be developed to modulate multivalent biomacromolecular interactions.
A boraamidinato ligand [PhB(N‐2,6‐iPr2C6H3)2]2? was employed to stabilize a new family of multiply bonded dimolybdenum complexes [MoCl(μ‐κ2‐PhB(N‐2,6‐iPr2C6H3)2)]2 ( 4 ) and [Mo(μ‐κ2‐PhB(N‐2,6‐iPr2C6H3)2)]2n? (n=0 ( 5 ), 1 ( 6 ), 2 ( 7 )), with the respective formal Mo?Mo bond orders of 3, 4, 4.5, and 5. Each metal center in 5 – 7 is two‐coordinate with respect to the ligands. Of particular interest is the quadruply bonded dimolybdenum complex 5 , featuring an unprecedented angular conformation. The bent Mo2N4 core of 5 distorts toward planarity upon reduction. As a result, compound 7 features a planar Mo2N4 core, while that of 6 is still bent but less significantly than that of 5 . Additionally, the Mo?Mo bond lengths of 4 – 7 systematically decrease as the valency of the central Mo2 units decreases. Complex 7 features the shortest Mo?Mo bond length (2.0106(5) Å) yet reported. 相似文献