88 research outputs found
Tuning the β-turn segment in designed peptide β-hairpins: Construction of a stable type I′ β-turn nucleus and hairpin-helix transition promoting segments Ч
No full textDesigned octapeptides Boc-Leu-Val-Val-Aib-DXxx-Leu-Val-Val-OMe (DXxx = DAla, 3a;DVal, 3c and DPro, 5a) and Boc-Leu-Phe-Val-Aib-DAla-Leu-Phe-Val-OMe (3b) have been investigated to construct models of a stable type I′ β-turn nucleated hairpin and to generate systems for investigating helix-hairpin conformational transitions. Peptide 5a, which contains a central Aib-DPro segment, is shown to adopt a stable type I′ β-turn nucleated hairpin structure, stabilized by four cross-strand hydrogen bonds. The stability of the structure in diverse solvents is established by the observation of all diagnostic NOEs expected in a β-hairpin conformation. Replacement of DPro5 by DAla/DVal (3a-c) results in sequences that form β-hairpins in hydrogen bonding solvents like CD3OH and DMSO-d6. However, in CDCl3 evidence for population of helical conformations is obtained. Peptide 6b (Boc-Leu-Phe-Val-Aib-Aib-Leu-Phe-Val-OMe), which contains a centrally positioned Aib-Aib segment, provides a clear example of a system, which exhibits a helical conformation in CDCl3 and a significant population of both helices and hairpins in CD3OH and DMSO-d6. The coexistence of multiple conformations is established by the simultaneous observation of diagnostic NOEs. Control over stereochemistry of the central β-turn permits generation of models for robust -hairpins and also for the construction of systems that may be used to probe helix-hairpin conformational transitions
Stabilizing effect of electrostatic vs. aromatic interactions in diproline nucleated peptide beta-hairpins
No full textThe contribution of Tyr-His vs. Cys-His interacting pairs to the scaffold stability of (D)Pro-(L)Pro nucleated peptide beta-hairpins has been examined. We present direct evidence for the superiority of the Cys-His pairs, mediated by sulphur-imidazole interactions, as added stabilizing agents of the beta-hairpin scaffold
The rα structure, chemical shift anisotropy, and the abnormal orientation of methyldichlorophosphine from the NMR spectrum
No full textNMR studies of methyldichlorophosphine have been undertaken in the nematic phase of mixed liquid crystals of opposite diamagnetic anisotropies. The rα structure is derived. The proton chemical-shift anisotropy has been determined from the studies without the use of a reference compound and without a change of experimental conditions. It is shown that the molecule orients in the liquid crystal with positive diamagnetic anisotropy in such a way that the C3 symmetry axis of the CH3P moiety is preferentially aligned perpendicular to the direction of the magnetic field, unlike other similar systems. This is interpreted in terms of the formation of a weak solvent-solute molecular complex. The heteronuclear indirect spin-spin coupling constants are determined. The sign of the two-bond JPH is found to be positive
Conformational properties and aggregation of homo-oligomeric beta(3)(R)-valine peptides in organic solvents
No full textThe conformational characteristics of protected homo-oligomeric Boc-beta(3)(R) Val](n)-OMe, n = 1, 2, 3, 4, 6, 9, and 12 have been investigated in organic solvents using nuclear magnetic resonance (NMR), Fourier transform infrared (FTIR) absorption spectroscopy and circular dichroism (CD) methods. The detailed H-1 NMR analysis of Boc-beta(3)(R)Val](12)-OMe reveals that the peptide aggregates extensively in CDCl3, but is disaggregated in 20%, (v/v) dimethyl sulfoxide (DMSO) in CDCl3 and in CD3OH. Limited assignment of the N-terminus NH groups, together with solvent dependence of NH chemical shifts and temperature coefficients provides evidence for 14-helix conformation in the 12-residue peptide. FTIR analysis in CHCl3 establishes that the onset of folding and aggregation, as evidenced by NH stretching bands at 3375 cm(-1) (intramolecular) and 3285 cm(-1) (intermolecular), begins at the level of the tetrapeptide. The observed CD bands, 214 nm (negative) and 198 nm (positive), support 14-helix formation in the 9 and 12 residue sequences. The folding and aggregation tendencies of homo-oligomeric alpha-, beta-, and gamma-residues is compared in the model peptides Boc-omega Val] omega-NHMe, omega = alpha, beta, and gamma and n = 1, 2, and 3. Analysis of the FTIR spectra in CHCl3, establish that the tendency to aggregate at the di and tripeptide level follows the order beta > alpha similar to gamma, while the tendency to fold follows the order gamma > beta > alpha
NMR analysis of aromatic interactions in designed peptide β-hairpins
No full textDesigned octapeptide β-hairpins containing a central DPro-Gly segment have been used as a scaffold to place the aromatic residues Tyr and Trp at various positions on the antiparallel β-strands. Using a set of five peptide hairpins, aromatic interactions have been probed across antiparallel β-sheets, in the non-hydrogen bonding position (Ac-L-Y-V-DP-G-L-Y/W-V-OMe: peptides 1 and 2), diagonally across the strands (Boc-Y/W-L-V-DP-G-W-L-V-OMe: peptides 3 and 6), and along the strands at positions i and i + 2 (Boc-L-L-V-DP-G-Y-L-W-OMe: peptide 4). Two peptides served as controls (Boc-L-L-V-DP-G-Y-W-V-OMe: peptide 5; Boc-L-Y-V-DP-G-L-L-V-OMe: peptide 7) for aromatic interactions. All studies have been carried out using solution NMR methods in CDCl3 + 10% DMSO-d6 and have been additionally examined in CD3OH for peptides 1 and 2. Inter-ring proton-proton nuclear Overhauser effects (NOEs) and upfield shifted aromatic proton resonances have provided firm evidence for specific aromatic interactions. Calculated NMR structures for peptides 1 and 2, containing aromatic pairs at facing non-hydrogen bonded positions, revealed that T-shaped arrangements of the interacting pairs of rings are favored, with ring current effects leading to extremely upfield chemical shifts and temperature dependences for specific aromatic protons. Anomalous far-UV CD spectra appeared to be a characteristic feature in peptides where the two aromatic residues are spatially proximal. The observation of the close approach of aromatic rings in organic solvents suggests that interactions of an electrostatic nature may be favored. This situation may be compared to the case of aqueous solutions, where clustering of aromatic residues is driven by solvophobic (hydrophobic) forces
Synthesis of 2-deoxy cyclic and linear oligosaccharides by oligomerization of monomers
No full textCyclic and linear oligosaccharides constituted with 2-deoxy sugar units are synthesized by an oligomerization reaction involving activated thioglycoside monomers, consisting of a 2-deoxy sugar unit. The oligomerization promoter plays an important role in the formation of either the cyclic- or the linear oligosaccharides. Encapsulation abilities of a 2-deoxy cyclic hexamer with p-nitrophenot, by a H-1 NMR method, showed complexation of the guest molecule with the host molecule
Design of a Peptide Hairpin Containing a Central Three-Residue Loop
No full textThe construction of a designed -hairpin structure, containing a central three-residue loop has been successfully achieved in the synthetic nonapeptide (2). The design is based on expanding the two-residue loop established in the peptide -hairpin (1). Characterization of the registered -hairpins in peptides 1 and 2 is based on the observation of key nuclear Overhauser effects (NOEs) in and . Solvent titration and temperature dependence of NH chemical shifts establish the identity of NH groups involved in interstrand hydrogen bonding. In peptide 2, the antiparallel registry is maintained, with the formation of a loop, stabilized by a hydrogen bond between Val3 CO and Leu7 NH groups and a hydrogen bond between CO and NH groups . NMR derived structures suggest that in peptide 2, adopts an conformation. In peptide 1, the segment adopts a type II' -turn. Replacement of in peptide 2 by in peptide 3 yields a -hairpin conformation, with a central two-residue loop. Strand slippage at the C-terminus results in altered registry of the antiparallel strands
Design of a peptide hairpin containing a central three-residue loop
No full textThe construction of a designed β-hairpin structure, containing a central three-residue loop has been successfully achieved in the synthetic nonapeptide Boc-Leu-Phe-Val-DPro-LPro-DAla-Leu-Phe-Val-OMe (2). The design is based on expanding the two-residue loop established in the peptide β-hairpin Boc-Leu-Phe-Val-DPro-LPro-Leu-Phe-Val-OMe (1). Characterization of the registered β-hairpins in peptides 1 and 2 is based on the observation of key nuclear Overhauser effects (NOEs) in CDCl3 and CD3OH. Solvent titration and temperature dependence of NH chemical shifts establish the identity of NH groups involved in interstrand hydrogen bonding. In peptide 2, the antiparallel registry is maintained, with the formation of a DPro-LPro-DAla loop, stabilized by a 5→1 hydrogen bond between Val3 CO and Leu7 NH groups (C13, β-turn) and a 3→1 hydrogen bond between dPro4 CO and DAla6 NH groups (C7, γ-turn). NMR derived structures suggest that in peptide 2, DAla(6) adopts an αL conformation. In peptide 1, the DPro-LPro segment adopts a type II' β-turn. Replacement of DAla (6) in peptide 2 by lAla in peptide 3 yields a β-hairpin conformation, with a central DPro-LPro two-residue loop. Strand slippage at the C-terminus results in altered registry of the antiparallel strands
Analogues
No full textTemplate-assisted formation of multicomponent Pd6 coordination prisms and formation of their self-templated triply interlocked Pd12 analogues in the absence of an external template have been established in a single step through PdN/PdO coordination. Treatment of cis-[Pd(en)(NO3)2] with K3tma and linear pillar 4,4′-bpy (en=ethylenediamine, H3tma=benzene-1,3,5-tricarboxylic acid, 4,4′-bpy=4,4′-bipyridine) gave intercalated coordination cage [{Pd(en)}6(bpy)3(tma)2]2[NO3]12 (1) exclusively, whereas the same reaction in the presence of H3tma as an aromatic guest gave a H3tma-encapsulating non-interlocked discrete Pd6 molecular prism [{Pd(en)}6(bpy)3(tma)2(H3tma)2][NO3]6 (2). Though the same reaction using cis-[Pd(NO3)2(pn)] (pn=propane-1,2-diamine) instead of cis-[Pd(en)(NO3)2] gave triply interlocked coordination cage [{Pd(pn)}6(bpy)3(tma)2]2[NO3]12 (3) along with non-interlocked Pd6 analogue [{Pd(pn)}6(bpy)3(tma)2](NO3)6 (3′), and the presence of H3tma as a guest gave H3tma-encapsulating molecular prism [{Pd(pn)}6(bpy)3(tma)2(H3tma)2][NO3]6 (4) exclusively. In solution, the amount of 3′ decreases as the temperature is decreased, and in the solid state 3 is the sole product. Notably, an analogous reaction using the relatively short pillar pz (pz=pyrazine) instead of 4,4′-bpy gave triply interlocked coordination cage [{Pd(pn)}6(pz)3(tma)2]2[NO3]12 (5) as the single product. Interestingly, the same reaction using slightly more bulky cis-[Pd(NO3)2(tmen)] (tmen=N,N,N′,N′-tetramethylethylene diamine) instead of cis-[Pd(NO3)2(pn)] gave non-interlocked [{Pd(tmen)}6(pz)3(tma)2][NO3]6 (6) exclusively. Complexes 1, 3, and 5 represent the first examples of template-free triply interlocked molecular prisms obtained through multicomponent self-assembly. Formation of the complexes was supported by IR and multinuclear NMR (1H and 13C) spectroscopy. Formation of guest-encapsulating complexes (2 and 4) was confirmed by 2D DOSY and ROESY NMR spectroscopic analyses, whereas for complexes 1, 3, 5, and 6 single-crystal X-ray diffraction techniques unambiguously confirmed their formation. The gross geometries of H3tma-encapsulating complexes 2 and 4 were obtained by universal force field (UFF) simulations
Effect of methylene group insertions on the structural rigidity of Aib containing helices
No full textNonprotein amino acids are being extensively used in the design of synthetic peptides to create new structure mimics. In this study we report the effect of methylene group insertions in a heptapeptide Boc-Ala(1)-Leu(2)-Aib(3)-Xxx(4)-Ala(5)-Leu(6)-Aib(7)-OMe which nicely folds into a mixed 3(10)-/-helical structure when Xxx= Ala. Analogs of this peptide have been made and studied by replacing central Xxx(4) residue with Glycine (-residue), -Alanine (-la), -aminobutyric acid (Gaba), and epsilon-aminocaproic acid (epsilon-Aca). NMR and circular dichroism were used to study the solution structure of these peptides. Crystals of the peptides containing alanine, -la, and Gaba reveal that increasing the number of central methylene (-CH2-) groups introduces local perturbations even as the helical structure is retained. (c) 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 104: 720-732, 2015
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