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Helical Peptides (helical + peptide)

Distribution by Scientific Domains

Chemistry	88%

Selected Abstracts

Thermal Stability of Dehydrophenylalanine-Containing Model Peptides as Probed by Infrared Spectroscopy: a Case Study of an , -Helical and a 310 -Helical Peptide

CHEMISTRY & BIODIVERSITY, Issue 3 2006
Alka Gupta
Abstract The temperature-dependent secondary-structural changes in the two known helical model peptides Boc-Val-,Phe-Ala-Leu-Gly-OMe (1; , -helical) and Boc-Leu-Phe-Ala-,Phe-Leu-OMe (2; 310 -helical), which both comprise a single dehydrophenylalanine (,Phe) residue, were investigated by means of FT-IR spectroscopy (peptide film on KBr). Both the first-order and the better-resolved second-order derivative IR spectra of 1 and 2 were analyzed. The ,(NH) (3240,3340,cm,1), the Amide-I (1600,1700,cm,1), and the Amide-II (1510,1580,cm,1) regions of 1 and 2 showed significant differences in thermal-denaturation experiments (22°,144°), with the 310 -helical peptide (2) being considerably more stable. This observation was rationalized by different patterns and strengths of intramolecular H-bonds, and was qualitatively related to the different geometries of the peptides. Also, a fair degree of residual secondary-structural elements were found even in the ,denatured' states above 104° (1) or 134° (2). [source]

Comment on "Aromatic-Backbone Interactions in Model ,-Helical Peptides" [Palermo et al., J Comput Chem 2007, 28, 1208]

JOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 1 2008
Tanja Van Mourik
Abstract Palermo et al. have recently published a method to correct for intramolecular basis set superposition errors (J Comput Chem 2007, 28, 1208) in intramolecular interactions occurring in peptides. By considering the intermolecular equivalent of this method, it is shown that the method presented by Palermo et al. underestimates the magnitude of the intramolecular BSSE. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008 [source]

Reply to "Comment on Aromatic-Backbone Interactions in Model ,-Helical Peptides"

JOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 1 2008
József Csontos
Abstract In response to Van Mourik's comments on our paper (J Comput Chem 2007, 28, 1208.) we present an extended version of our rotation method. We also prove that intramolecular interaction energies as well the basis set superposition errors calculated with our rotation method are comparable with those obtained by the counterpoise method of Boys and Bernardi (Mol Phys 1970, 19, 533). In intramolecular interaction energy calculations, if the interacting groups are in proximity, our rotation method is recommended to avoid artificial interactions, which can be induced by fragmentation. © 2007 Wiley Periodicals, Inc.J Comput Chem, 2008 [source]

RNA Grooves Can Accommodate Disulfide-Bridged Bundles of ,-Helical Peptides

CHEMBIOCHEM, Issue 6 2010
Soonsil Hyun Dr.
Feelin' groovy: A strategy for chemical stapling increases structural as well as chemical stability of helical peptides. Using an amphiphilic peptide with Leu/Lys, two Leu residues were replaced by Cys. Helical bundle peptides were generated by oxidative disulfide bond formation. One of these has a Kd as low as 21 pM against hairpin targets. This observation demonstrates that the groove in small hairpin RNA has sufficient room to contain a helical bundle peptide. [source]

Distance dependence of long-range electron transfer through helical peptides,

JOURNAL OF PEPTIDE SCIENCE, Issue 2 2008
Minako Kai
Abstract Helical peptides of 8mer, 16mer, and 24mer carrying a disulfide group at the N -terminal and a ferrocene moiety at the C -terminal were synthesized, and they were self-assembled on gold by a sulfur,gold linkage. Infrared reflection,absorption spectroscopy and ellipsometry confirmed that they formed a monolayer with upright orientation. Cyclic voltammetry showed that the electron transfer from the ferrocene moiety to gold occurred even with the longest 24mer peptide. Chronoamperometry and electrochemical impedance spectroscopy were carried out to determine the standard electron transfer rate constants. It was found that the dependence of the electron-transfer rates on the distance was significantly weak with the extension of the chain from 16mer to 24mer (decay constant , = 0.02,0.04). This dependence on distance cannot be explained by an electron tunneling mechanism even if increased hydrogen-bonding cooperativity or molecular dynamics is considered. It is thus concluded that this long-range electron transfer is operated by an electron hopping mechanism. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd. [source]

Rapid and sustained improvement in bone and cartilage turnover markers with the anti,interleukin-6 receptor inhibitor tocilizumab plus methotrexate in rheumatoid arthritis patients with an inadequate response to methotrexate: Results from a substudy of the multicenter double-blind, placebo-controlled trial of tocilizumab in inadequate responders to methotrexate alone,

ARTHRITIS & RHEUMATISM, Issue 1 2010
Patrick Garnero
Objective To investigate the effects of tocilizumab (TCZ) added to a stable dosage of methotrexate (MTX) on biochemical markers of bone and cartilage metabolism in patients in the multicenter double-blind, placebo-controlled OPTION (Tocilizumab Pivotal Trial in Methotrexate Inadequate Responders) study who have moderate-to-severe rheumatoid arthritis (RA) and an inadequate response to MTX. Methods Included in this study were 416 of the 623 patients with active RA enrolled in the OPTION study. Patients were randomized to receive TCZ (4 mg/kg or 8 mg/kg) or placebo intravenously every 4 weeks, with MTX continued at the stable prestudy doses (10,25 mg for 20 weeks, with a final followup at week 24). Serum biochemical markers of bone formation (osteocalcin, N-terminal propeptide of type I collagen [PINP]), bone resorption (C-terminal crosslinking telopeptide of type I collagen [CTX-I] and C-terminal crosslinking telopeptide of type I collagen generated by matrix metalloproteinases [ICTP]), cartilage metabolism (N-terminal propeptide of type IIA collagen [PIIANP]), collagen helical peptide [HELIX-II]), and matrix metalloproteinase 3 (MMP-3) were measured at baseline and at weeks 4, 16, and 24. Results TCZ induced marked dose-dependent reductions in PIIANP, HELIX-II, and MMP-3 levels at week 4 that were maintained until week 24, an effect associated with increased levels of bone formation markers that were significant as compared with placebo only for PINP and only at 4 weeks (P < 0.01 for both TCZ doses). TCZ induced significant decreases in the bone degradation markers CTX-I and ICTP, providing initial evidence of a beneficial effect on bone turnover. TCZ-treated patients who met the American College of Rheumatology 50% improvement criteria (achieved an ACR50 response) or achieved clinical remission (as determined by a Disease Activity Score in 28 joints <2.6) at week 24 had greater reductions in ICTP, HELIX-II, and MMP-3 levels as compared with ACR50 nonresponders. Conclusion TCZ combined with MTX reduces systemic bone resorption, cartilage turnover, and proteolytic enzyme MMP-3 levels, which provides evidence of a limitation of joint damage and possible beneficial effects on skeletal structure in patients with established moderate-to-severe RA. [source]

Chiral interaction in Gly-capped N-terminal motif of 310 -helix and domino-type induction in helix sense

BIOPOLYMERS, Issue 4 2006
Naoki Ousaka
Abstract Chiral interaction of helical peptide with chiral molecule, and concomitant induction in its helix sense have been demonstrated in optically inactive nonapeptide (1) possessing Gly at its N-terminus: H,Gly,(,ZPhe,Aib)4,OCH3 (1: ,ZPhe = Z-dehydrophenylalanine; Aib = ,-aminoisobutyric acid). Spectroscopic measurements [mainly nuclear magnetic resonance (NMR) and circular diochroism (CD)] as well as theoretical simulation have been carried out for that purpose. Peptide 1 in the 310 -helix tends to adopt preferentially a right-handed screw sense by chiral Boc- L -amino acid (Boc: t -butoxycarbonyl). Induction in the helix sense through the noncovalent chiral domino effect should be derived primarily from the complex supported by the three-point coordination on the N-terminal sequence. Thus the 310 -helical terminus consisting of only ,-amino acid residues enables chiral recognition of the Boc-amino acid molecule, leading to modulation of the original chain asymmetry. Dynamics in the helix-sense induction also have been discussed on the basis of a low-temperature NMR study. Furthermore, the inversion of induced helix sense has been achieved through solvent effects. © 2006 Wiley Periodicals, Inc. Biopolymers 83:337,351, 2006 This article was originally published online as an accepted preprint. The "Published Online" date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com [source]

Crystal structure of achiral nonapeptide Boc,(Aib,,zPhe)4,Aib,OMe at atomic resolution: Evidence for a 310 -helix

BIOPOLYMERS, Issue 3 2003
Yoshihito Inai
Abstract An x-ray crystallographic analysis was carried out for Boc,(Aib,,ZPhe)4,Aib,OMe (1: Boc = t -butoxycarbonyl; Aib = ,-aminoisobutyric acid; ,ZPhe = Z -,,,-didehydrophenylalanine) to provide the precise conformational parameters of the octapeptide segment ,(Aib,,ZPhe)4,. Peptide 1 adopted a typical 310 -helical conformation characterized by ,,, = ±55.8° (50°,65°), ,,, = ±26.7° (15°,45°), and ,,, = ±179.5° (168°,188°) for the average values of the ,(Aib,,ZPhe)4, segment (the range of the eight values). The 310 -helix contains 3.1 residues per turn, being close to the "perfect 310 -helix" characterized by 3.0 residues per turn. NMR and Fourier transform infrared (FTIR) spectroscopy revealed that the 310 -helical conformation at the atomic resolution is essentially maintained in solution. Energy minimization of peptide 1 by semiempirical molecular orbital calculation converged to a 310 -helical conformation similar to the x-ray crystallographic 310 -helix. The preference for a 310 -helix in the ,(Aib,,ZPhe)4, segment is ascribed to strong inducers of the 310 -helix inherent in Aib and ,ZPhe residues,in particular, the Aib residues tend to stabilize a 310 -helix more effectively. Therefore, the ,(Aib,,ZPhe)4, segment is useful to rationally design an optically inactive 310 -helical backbone, which will be of great importance to provide novel insights into noncovalent and covalent chiral interactions of a helical peptide with a chiral molecule. © 2003 Wiley Periodicals, Inc. Biopolymers 70: 310,322, 2003 [source]

Molecular Characterization of the NCoA-1,STAT,6 Interaction

CHEMBIOCHEM, Issue 8 2008
Markus Seitz
Abstract Many protein,protein interactions involved in cell signalling, cell adhesion and regulation of transcription are mediated by short ,-helical recognition motifs with the sequence Leu-Xaa-Xaa-Leu-Leu (LXXLL, where Xaa is any amino acid). Originally observed in cofactors that interact with hormone-activated nuclear receptors, LXXLL motifs are now known to occur in many transcription factors, including the STAT family, which transmit signals from activated cytokine receptors at the cell surface to target genes in the nucleus. STAT,6 becomes activated in response to IL-4 and IL-13, which regulate immune and anti-inflammatory responses. Structural studies have revealed how an LXXLL motif located in 2.5 turns of an ,-helical peptide derived from STAT,6 provide contacts through the leucine side chains to the coactivator of transcription, NCoA-1. However, since many protein,protein interactions are mediated by LXXLL motifs, it is important to understand how specificity is achieved in this and other signalling pathways. Here, we show that energetically important contacts between STAT,6 and NCoA-1 are made in residues that flank the LXXLL motif, including the underlined residues in the sequence LLPPTEQDLTKLL. We also demonstrate how the affinity for NCoA-1 of peptides derived from this region of STAT,6 can be significantly improved by optimising knobs-into-holes contacts on the surface of the protein. The results provide important new insights into the origins of binding specificity, and might be of practical value in the design of novel small-molecule inhibitors of this important protein,protein interaction. [source]

Thermal Stability of Dehydrophenylalanine-Containing Model Peptides as Probed by Infrared Spectroscopy: a Case Study of an , -Helical and a 310 -Helical Peptide

Ionization efficiency of ,-helical peptides in laser desorption/ionization mass spectrometry

JOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 7 2009
Yasushi Shigeri
[source]

Distance dependence of long-range electron transfer through helical peptides,

Crystal-state 3D-structural characterization of novel 310 -helical peptides

JOURNAL OF PEPTIDE SCIENCE, Issue 10 2003
Dr Marco Crisma
Abstract The crystal-state conformations of two octapeptides, pBrBz-(D -Iva)8 -OtBu (8I) and Ac-[L -(,Me)Val]8 -OH (8II), the heptapeptide Z-[L -(,Me)Val]7 -OH (7), the hexapeptide Z-[L -(,Me)Leu]6 -OtBu (6) and the tetrapeptide alkylamide Z-(Aib)2 - L -Glu(OMe)- L -Ala- L -Lol (5) were assessed by x-ray diffraction analyses. Two independent molecules are observed in the asymmetric unit of each L -(,Me)Val homo-peptide. All four homo-peptides are folded in a regular 310 -helical structure (only the C -terminal H-bonded conformation of the D -Iva octapeptide is distorted to a type-I ,-turn). The hydroxyl groups of the C -terminal carboxyl moieties of the two L -(,Me)Val homo-peptides participate in an oxy-analogue of the type-III ,-turn conformation. While the two L -(,Me)Val 310 -helices are right-handed, the D -Iva and L -(,Me)Leu helices are left-handed. The tetrapeptide alkylamide is 310 -helical at the N -terminus, but it is mixed 310/,-helical at the C -terminus. Copyright © 2003 European Peptide Society and John Wiley & Sons, Ltd. [source]

A novel method of affinity-purifying proteins using a bis-arsenical fluorescein

PROTEIN SCIENCE, Issue 2 2000
Kurt S. Thorn
Abstract Genetically-encoded affinity tags constitute an important strategy for purifying proteins. Here, we have designed a novel affinity matrix based on the bis-arsenical fluorescein dye FlAsH, which specifically recognizes short ,-helical peptides containing the sequence CCXXCC (Griffin BA, Adams SR, Tsien RY, 1998, Science 281:269,212). We find that kinesin tagged with this cysteine-containing helix binds specifically to FlAsH resin and can be eluted in a fully active form. This affinity tag has several advantages over polyhistidine, the only small affinity tag in common use. The protein obtained with this single chromatographic step from crude Escherichia coli lysates is purer than that obtained with nickel affinity chromatography of 6xHis tagged kinesin. Moreover, unlike nickel affinity chromatography, which requires high concentrations of imidazole or pH changes for elution, protein bound to the FlAsH column can be completely eluted by dithiothreitol. Because of these mild elution conditions, FlAsH affinity chromatography is ideal for recovering fully active protein and for the purification of intact protein complexes. [source]

RNA Grooves Can Accommodate Disulfide-Bridged Bundles of ,-Helical Peptides

Probing the ,-Helical Structural Stability of Stapled p53 Peptides: Molecular Dynamics Simulations and Analysis

CHEMICAL BIOLOGY & DRUG DESIGN, Issue 4 2010
Zuojun Guo
Reactivation of the p53 cell apoptosis pathway through inhibition of the p53-hDM2 interaction is a viable approach to suppress tumor growth in many human cancers and stabilization of the helical structure of synthetic p53 analogs via a hydrocarbon cross-link (staple) has been found to lead to increased potency and inhibition of protein,protein binding (J. Am. Chem. Soc. 129: 5298). However, details of the structure and dynamic stability of the stapled peptides are not well understood. Here, we use extensive all-atom molecular dynamics simulations to study a series of stapled ,-helical peptides over a range of temperatures in solution. The peptides are found to exhibit substantial variations in predicted ,-helical propensities that are in good agreement with the experimental observations. In addition, we find significant variation in local structural flexibility of the peptides with the position of the linker, which appears to be more closely related to the observed differences in activity than the absolute ,-helical stability. These simulations provide new insights into the design of ,-helical stapled peptides and the development of potent inhibitors of ,-helical protein,protein interfaces. [source]

The Application of 199Hg NMR and 199mHg Perturbed Angular Correlation (PAC) Spectroscopy to Define the Biological Chemistry of HgII: A Case Study with Designed Two- and Three-Stranded Coiled Coils

CHEMISTRY - A EUROPEAN JOURNAL, Issue 33 2007
Olga Iranzo Dr.
Abstract The use of de novo designed peptides is a powerful strategy to elucidate HgII,protein interactions and to gain insight into the chemistry of HgII in biological systems. Cysteine derivatives of the designed ,-helical peptides of the TRI family [Ac-G-(LaKbAcLdEeEfKg)4 -G-NH2] bind HgII at high pH values and at peptide/HgII ratios of 3:1 with an unusual trigonal thiolate coordination mode. The resulting HgII complexes are good water-soluble models for HgII binding to the protein MerR. We have carried out a parallel study using 199Hg NMR and 199mHg perturbed angular correlation (PAC) spectroscopy to characterize the distinct species that are generated under different pH conditions and peptide TRI,L9C/HgII ratios. These studies prove for the first time the formation of [Hg{(TRI,L9C)2 -(TRI,L9CH)}], a dithiolate,HgII complex in the hydrophobic interior of the three-stranded coiled coil (TRI,L9C)3. 199Hg NMR and 199mHg PAC data demonstrate that this dithiolate,HgII complex is different from the dithiolate [Hg(TRI,L9C)2], and that the presence of third ,-helix, containing a protonated cysteine, breaks the symmetry of the coordination environment present in the complex [Hg(TRI,L9C)2]. As the pH is raised, the deprotonation of this third cysteine generates the trigonal thiolate,HgII complex Hg(TRI,L9C)3, on a timescale that is slower than the NMR timescale (0.01,10,ms). The formation of the species [Hg{(TRI,L9C)2(TRI,L9CH)}] is the result of a compromise between the high affinity of HgII to form dithiolate complexes and the preference of the peptide to form a three-stranded coiled coil. [source]