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P Balaram - One of the best experts on this subject based on the ideXlab platform.
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Peptide design. Helix–helix motifs in synthetic sequences
2016Co-Authors: Arindam Banerjee, A Raghothama S. B, P BalaramAbstract:Two centrally positioned á-aminoisobutyryl (Aib) residues have been used to stabilize distinct heptapeptide helical segments in the 15-residue synthetic sequence Boc-Met-Ala-Leu-Aib-Val-Ala-Leu-Acp-Val-Ala-Leu-Aib-Val-Ala-Phe-OMe. The helices are connected by the flexible linker å-aminocaproic acid (Acp). NMR studies in CDCl3 establish helical conformations for both independent segments as evidenced by NH–NH nuclear Overhauser effects (NOEs). The peptide strongly aggregates in CDCl3 with the NH groups of Met(1) and Ala(2) participating in intermolecular hydrogen bonds. In (CD3)2SO two solvated helical segments are supported by NMR results. Solvent dependent breakdown of aggregates on addition of (CD3)2SO to CDCl3 solutions is suggested by analysis of chemical shifts and temperature coefficients of NH protons. The observation of several interhelical NOEs in CDCl3, relatively few NOEs in 10 % (CD3)2SO–CDCl3 and their absence in (CD3)2SO provides a means of inferring helix orientations. While an antiparallel arrangement resulting in closed aggregate formation is suggested in CDCl3, a parallel solvated arrangement is favoured in (CD3)2SO
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structural characterization of folded and extended conformations in peptides containing γ amino acids with proteinogenic side chains crystal structures of γn αγ n and γγδγ sequences
New Journal of Chemistry, 2015Co-Authors: Madhusudana M B Reddy, Siddappa Chandrappa, Krishnayan Basuroy, Bhimareddy Dinesh, B Vasantha, Manjunath A Venkatesha, P BalaramAbstract:The crystal structures of nine peptides containing γ4Val and γ4Leu are described. The short sequences Boc-[γ4(R)Val]2-OMe 1, Boc-[γ4(R)Val]3-NHMe 2 and Boc-γ4(S)Val-γ4(R)Val-OMe 3 adopt extended apolar, sheet like structures. The tetrapeptide Boc-[γ4(R)Val]4-OMe 4 adopts an extended conformation, in contrast to the folded C14 helical structure determined previously for Boc-[γ4(R)Leu]4-OMe. The hybrid αγ sequence Boc-[Ala-γ4(R)Leu]2-OMe 5 adopts an S-shaped structure devoid of intramolecular hydrogen bonds, with both α residues adopting local helical conformations. In sharp contrast, the tetrapeptides Boc-[Aib-γ4(S)Leu]2-OMe 6 and Boc-[Leu-γ4(R)Leu]2-OMe 7 adopt folded structures stabilized by two successive C12 hydrogen bonds. γ4Val residues have also been incorporated into the strand segments of a crystalline octapeptide, Boc-Leu-γ4(R)Val-Val-DPro-Gly-Leu-γ4(R)Val-Val-OMe 8. The γγδγ tetrapeptide containing γ4Val and δ5Leu residues adopts an extended sheet like structure. The hydrogen bonding pattern at γ residues corresponds to an apolar sheet, while a polar sheet is observed at the lone δ residue. The transition between folded and extended structures at γ residues involves a change of the torsion angle from the gauche to the trans conformation about the Cβ–Cα bond.
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structural characterization of folded and extended conformations in peptides containing gamma amino acids with proteinogenic side chains crystal structures of gamma n alpha gamma n and gamma gamma delta gamma sequences
2015Co-Authors: Muthukurpalya Bhojegowd Madhusudana Reddy, Siddappa Chandrappa, Krishnayan Basuroy, Bhimareddy Dinesh, Manjunath A Venkatesha, Vasantha Basavalingappa, P BalaramAbstract:The crystal structures of nine peptides containing gamma(4)Val and gamma(4)Leu are described. The short sequences Boc-gamma(4)(R)Val](2)-OMe 1, Boc-gamma(4)(R)Val](3)-NHMe 2 and Boc-gamma(4)(S)Val-gamma(4)(R)Val-OMe 3 adopt extended apolar, sheet like structures. The tetrapeptide Boc-gamma(4)(R)Val](4)-OMe 4 adopts an extended conformation, in contrast to the folded C-14 helical structure determined previously for Boc-gamma(4)(R)Leu](4)-OMe. The hybrid alpha gamma sequence Boc-Ala-gamma(4)(R)Leu](2)-OMe 5 adopts an S-shaped structure devoid of intramolecular hydrogen bonds, with both alpha residues adopting local helical conformations. In sharp contrast, the tetrapeptides Boc-Aib-gamma(4)(S)Leu](2)-OMe 6 and Boc-Leu-gamma(4)(R)Leu](2)-OMe 7 adopt folded structures stabilized by two successive C-12 hydrogen bonds. gamma(4)Val residues have also been incorporated into the strand segments of a crystalline octapeptide, Boc-Leu-gamma(4)(R)Val-Val-(D)Pro-Gly-Leu-gamma(4)(R)Val-Val-OMe 8. The gamma gamma delta gamma tetrapeptide containing gamma(4)Val and delta(5)Leu residues adopts an extended sheet like structure. The hydrogen bonding pattern at gamma residues corresponds to an apolar sheet, while a polar sheet is observed at the lone delta residue. The transition between folded and extended structures at gamma residues involves a change of the torsion angle from the gauche to the trans conformation about the C-beta-C-alpha bond.
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aromatic interactions in model peptide β hairpins ring current effects on proton chemical shifts
Biopolymers, 2012Co-Authors: Appavu Rajagopal, Srinivasarao Raghothama, Subrayashastry Aravinda, Narayanaswamy Shamala, P BalaramAbstract:Crystal structures of eight peptide β-hairpins in the sequence Boc-Leu-Phe-Val-Xxx-Yyy-Leu-Phe-Val-OMe revealed that the Phe(2) and Phe(7) aromatic rings are in close spacial proximity, with the centroid–centroid distance (Rcen) of 4.4–5.4 A between the two phenyl rings. Proton NMR spectra in chloroform and methanol solution reveal a significant upfield shift of the Phe(7) Cδ,δ′H2 protons (6.65–7.04 ppm). Specific assignments of the aromatic protons have been carried out in the peptide Boc-Leu-Phe-Val-DPro-LPro-Leu-Phe-Val-OMe (6). The anticipated ring current shifts have been estimated from the aromatic ring geometrics observed in crystals for all eight peptides. Only one of the Cδ,δ′H proton lies in the shielding zone with rapid ring flipping, resulting in averaging between the two extreme chemical shifts. An approximate estimate of the population of conformations, which resemble crystal state orientation, may be obtained. Key nuclear Overhauser effects (NOEs) between facing Phe side chains provide support for close similarity between the solid state and solution conformation. Temperature dependence of aromatic ring proton chemical shift and line widths for peptide 6 (Boc-Leu-Phe-Val-DPro-LPro-Leu-Phe-Val-OMe) and the control peptide Boc-Leu-Val-Val-DPro-Gly-Leu-Phe-Val-OMe establish an enhanced barrier to ring flipping when the two Phe rings are in proximity. Modeling studies suggest that small, conformational adjustment about CαCβ (χ1) and CβCγ (χ2) bonds of both the Phe residues may be required in order to permit unhindered, uncorrelated flipping of both the Phe rings. The maintenance of the specific aromatic ring orientation in organic solvents provides evidence for significant stabilizing interaction. © 2011 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 98: 185–194, 2012.
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solution conformation of a tetradecapeptide stabilized by two di n propyl glycine residues
Journal of Peptide Science, 2010Co-Authors: Balaji R Rao, Vijayalekshmi Sarojini, Srinivasarao Ragothama, P BalaramAbstract:The solution conformation of a designed tetradecapeptide Boc-Val-Ala-Leu-Dpg-Val-Ala-Leu-Val-Ala-Leu-Dpg-Val-Ala-Leu-OMe (Dpg-14) containing two di-n-propyl glycine (Dpg) residues has been investigated by H-1 NMR and circular dichroism in organic solvents. The peptide aggregates formed at a concentration of 3 mm in the apolar solvent CDCl3 were broken by the addition of 12% v/v of the more polar solvent DMSO-d(6). Successive NiH Ni+1H NOEs observed over the entire length of the sequence in this solvent mixture together with the observation of several characteristic medium-range NOEs support a major population of continuous helical conformations for Dpg-14. Majority of the observed coupling constants ((3)(alpha)(JNHC)(H)) also support phi values in the helical conformation. Circular dichroism spectra recorded in methanol and propan-2-ol give further support in favor of helical conformation for Dpg-14 and the stability of the helix at higher temperature. Copyright (C) 2010 European Peptide Society and John Wiley & Sons, Ltd.
Yajun Zheng - One of the best experts on this subject based on the ideXlab platform.
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purification and identification of antioxidative peptides of palm kernel expeller glutelin 1 hydrolysates
RSC Advances, 2017Co-Authors: Yajun Zheng, Yufeng ZhangAbstract:To obtain hydrolysates with high antioxidant activity and hydrolysis degree, palm kernel expeller glutelin-1 was hydrolyzed by pepsin assisted with high pressure pretreatment. The results of orthogonal experiment revealed that the optimum enzymatic hydrolysis conditions were as follows: enzymes concentration of 2 g/100 g, hydrolysis time of 4 h, temperature 37 °C and pH 2.0. Palm kernel expeller glutelin-1 hydrolysate was separated by ultrafiltration, Sephadex G-15 gel chromatography and reversed-phase high performance liquid chromatography. Finally, four peptides Thr-Val-Phe-Asp-Gly-Glu-Leu-Arg (935.5 Da), Ala-Asp-Val-Phe-Asn-Pro-Arg (818.7 Da), Cys-Ala-Gly-Val-Ser-Ala-Ile-Arg (832.4 Da) and Leu-Val-Tyr-Ile-Ile-Gln-Gly-Arg (819.4 Da) were identified and their IC50 values on hydroxyl radical scavenging activities were 38.22 ± 2.22, 22.16 ± 1.22, 31.19 ± 1.67 and 12.85 ± 0.23 μg mL−1, respectively. Furthermore, these peptides were chemically synthesized and the peptides ADVFNPR and CAGVSAIR showed good stability against simulated gastrointestinal protease digestion.
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purification characterization synthesis in vitro ace inhibition and in vivo antihypertensive activity of bioactive peptides derived from oil palm kernel glutelin 2 hydrolysates
Journal of Functional Foods, 2017Co-Authors: Yajun Zheng, Yan Li, Youlin Zhang, Xiaohui Ruan, Runguang ZhangAbstract:Abstract Palm kernel expeller glutelin-2 hydrolysates (PKEGH) with high ACE-inhibitory activity (80.24%) were obtained by the sequential digestion with alcalase, flavourzyme, pepsin and trypsin assisted by high pressure pretreatment. PKEGH were separated by ultrafiltration, Sephadex G-25 gel chromatography and RP-HPLC. Finally four novel ACE-inhibitory peptides (Ala-Asp-Val-Phe-Asn-Pro-Arg, Val-Val-Leu-Tyr-Lys, Leu-Pro-Ile-Leu-Arg and Val-Ile-Glu-Pro-Arg) were identified, of which Val-Val-Leu-Tyr-Lys showed the highest activity (IC50: 533.9 μM). All the four peptides exhibited potent non-competitive ACE inhibition and relatively good stability against gastrointestinal enzymes digestion. Moreover, these peptides significantly lowered the endothelin-1 content in EA.hy926 cells without significant cytotoxicity, and protected vascular endothelial cells from reactive oxygen species mediated damage. Furthermore, the PKEGH and individual ACE-inhibitory peptides identified from it showed chronic antihypertensive effects in spontaneously hypertensive rats after several days/weeks administration. Result showed that Palm kernel expeller glutelin-2 could be effectively converted to produce ACE-inhibitory or antihypertensive peptides.
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purification characterization synthesis in vitro ace inhibition and in vivo antihypertensive activity of bioactive peptides derived from oil palm kernel glutelin 2 hydrolysates
Journal of Functional Foods, 2017Co-Authors: Yajun Zheng, Youlin Zhang, Xiaohui Ruan, Runguang ZhangAbstract:Abstract Palm kernel expeller glutelin-2 hydrolysates (PKEGH) with high ACE-inhibitory activity (80.24%) were obtained by the sequential digestion with alcalase, flavourzyme, pepsin and trypsin assisted by high pressure pretreatment. PKEGH were separated by ultrafiltration, Sephadex G-25 gel chromatography and RP-HPLC. Finally four novel ACE-inhibitory peptides (Ala-Asp-Val-Phe-Asn-Pro-Arg, Val-Val-Leu-Tyr-Lys, Leu-Pro-Ile-Leu-Arg and Val-Ile-Glu-Pro-Arg) were identified, of which Val-Val-Leu-Tyr-Lys showed the highest activity (IC50: 533.9 μM). All the four peptides exhibited potent non-competitive ACE inhibition and relatively good stability against gastrointestinal enzymes digestion. Moreover, these peptides significantly lowered the endothelin-1 content in EA.hy926 cells without significant cytotoxicity, and protected vascular endothelial cells from reactive oxygen species mediated damage. Furthermore, the PKEGH and individual ACE-inhibitory peptides identified from it showed chronic antihypertensive effects in spontaneously hypertensive rats after several days/weeks administration. Result showed that Palm kernel expeller glutelin-2 could be effectively converted to produce ACE-inhibitory or antihypertensive peptides.
Thomas Hofmann - One of the best experts on this subject based on the ideXlab platform.
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structures sensory activity and dose response functions of 2 5 diketopiperazines in roasted cocoa nibs theobroma cacao
Journal of Agricultural and Food Chemistry, 2005Co-Authors: Timo D. Stark, Thomas HofmannAbstract:The taste compounds inducing the blood-like, metallic bitter taste sensation reported recently for a dichloromethane extract prepared from roasted cocoa nibs were identified as a series of 25 diketopiperazines by means of HPLC degustation, LC−MS/MS, and independent synthesis. Among these 25 compounds, 13 cis-configured diketopiperazines, namely, cyclo(l-IIe-l-Phe), cyclo(l-Val-l-Leu), cyclo(l-Pro-l-Pro), cyclo(l-IIe-l-Pro), cyclo(l-Val-l-Tyr), cyclo(l-Ala-l-Tyr), cyclo(l-Phe-l-Ser), cyclo(l-Ala-l-IIe), cyclo(l-Leu-l-Phe), cyclo(l-Pro-l-Val), cyclo(l-Pro-l-Thr), cyclo(l-Pro-l-Tyr), and cyclo(l-Val-l-Val) were identified for the first time in cocoa. In addition, the taste recognition thresholds for the metallic as well as the bitter taste of the diketopiperazines were determined, and after quantitative analysis by using two diastereomeric diketopiperazines as the internal standards, the sensory impact of the diketopiperazines was evaluated on the basis of their dose-over-threshold (DoT) factors calculated a...
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structures sensory activity and dose response functions of 2 5 diketopiperazines in roasted cocoa nibs theobroma cacao
Journal of Agricultural and Food Chemistry, 2005Co-Authors: Timo D. Stark, Thomas HofmannAbstract:The taste compounds inducing the blood-like, metallic bitter taste sensation reported recently for a dichloromethane extract prepared from roasted cocoa nibs were identified as a series of 25 diketopiperazines by means of HPLC degustation, LC-MS/MS, and independent synthesis. Among these 25 compounds, 13 cis-configured diketopiperazines, namely, cyclo(L-IIe-L-Phe), cyclo(L-Val-L-Leu), cyclo(L-Pro-L-Pro), cyclo(L-IIe-L-Pro), cyclo(L-Val-L-Tyr), cyclo(L-Ala-L-Tyr), cyclo(L-Phe-L-Ser), cyclo(L-Ala-L-IIe), cyclo(L-Leu-L-Phe), cyclo(L-Pro-L-Val), cyclo(L-Pro-L-Thr), cyclo(L-Pro-L-Tyr), and cyclo(L-Val-L-Val) were identified for the first time in cocoa. In addition, the taste recognition thresholds for the metallic as well as the bitter taste of the diketopiperazines were determined, and after quantitative analysis by using two diastereomeric diketopiperazines as the internal standards, the sensory impact of the diketopiperazines was evaluated on the basis of their dose-over-threshold (DoT) factors calculated as the ratio of the concentration and the threshold concentration of a compound. These data revealed DoT factors above 1.0 exclusively for cis-cyclo(L-Pro-L-Val), cis-cyclo(L-Val-L-Leu), cis-cyclo(L-Ala-L-Ile), cis-cyclo(L-Ala-L-Leu), and cis-cyclo(L-Ile-L-Pro), whereas all of the other diketopiperazines were present below their individual bitter taste threshold concentrations and should therefore not contribute to the cocoa taste. Because the DoT factors do not consider the nonlinear relationship between the concentration and gustatory response of an individual compound, we, for the first time, report on the recording of dose/response functions describing the human bitter taste perception of diketopiperazines more precisely.
Runguang Zhang - One of the best experts on this subject based on the ideXlab platform.
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purification characterization synthesis in vitro ace inhibition and in vivo antihypertensive activity of bioactive peptides derived from oil palm kernel glutelin 2 hydrolysates
Journal of Functional Foods, 2017Co-Authors: Yajun Zheng, Yan Li, Youlin Zhang, Xiaohui Ruan, Runguang ZhangAbstract:Abstract Palm kernel expeller glutelin-2 hydrolysates (PKEGH) with high ACE-inhibitory activity (80.24%) were obtained by the sequential digestion with alcalase, flavourzyme, pepsin and trypsin assisted by high pressure pretreatment. PKEGH were separated by ultrafiltration, Sephadex G-25 gel chromatography and RP-HPLC. Finally four novel ACE-inhibitory peptides (Ala-Asp-Val-Phe-Asn-Pro-Arg, Val-Val-Leu-Tyr-Lys, Leu-Pro-Ile-Leu-Arg and Val-Ile-Glu-Pro-Arg) were identified, of which Val-Val-Leu-Tyr-Lys showed the highest activity (IC50: 533.9 μM). All the four peptides exhibited potent non-competitive ACE inhibition and relatively good stability against gastrointestinal enzymes digestion. Moreover, these peptides significantly lowered the endothelin-1 content in EA.hy926 cells without significant cytotoxicity, and protected vascular endothelial cells from reactive oxygen species mediated damage. Furthermore, the PKEGH and individual ACE-inhibitory peptides identified from it showed chronic antihypertensive effects in spontaneously hypertensive rats after several days/weeks administration. Result showed that Palm kernel expeller glutelin-2 could be effectively converted to produce ACE-inhibitory or antihypertensive peptides.
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purification characterization synthesis in vitro ace inhibition and in vivo antihypertensive activity of bioactive peptides derived from oil palm kernel glutelin 2 hydrolysates
Journal of Functional Foods, 2017Co-Authors: Yajun Zheng, Youlin Zhang, Xiaohui Ruan, Runguang ZhangAbstract:Abstract Palm kernel expeller glutelin-2 hydrolysates (PKEGH) with high ACE-inhibitory activity (80.24%) were obtained by the sequential digestion with alcalase, flavourzyme, pepsin and trypsin assisted by high pressure pretreatment. PKEGH were separated by ultrafiltration, Sephadex G-25 gel chromatography and RP-HPLC. Finally four novel ACE-inhibitory peptides (Ala-Asp-Val-Phe-Asn-Pro-Arg, Val-Val-Leu-Tyr-Lys, Leu-Pro-Ile-Leu-Arg and Val-Ile-Glu-Pro-Arg) were identified, of which Val-Val-Leu-Tyr-Lys showed the highest activity (IC50: 533.9 μM). All the four peptides exhibited potent non-competitive ACE inhibition and relatively good stability against gastrointestinal enzymes digestion. Moreover, these peptides significantly lowered the endothelin-1 content in EA.hy926 cells without significant cytotoxicity, and protected vascular endothelial cells from reactive oxygen species mediated damage. Furthermore, the PKEGH and individual ACE-inhibitory peptides identified from it showed chronic antihypertensive effects in spontaneously hypertensive rats after several days/weeks administration. Result showed that Palm kernel expeller glutelin-2 could be effectively converted to produce ACE-inhibitory or antihypertensive peptides.
Padmanabhan Balaram - One of the best experts on this subject based on the ideXlab platform.
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directing peptide conformation with centrally positioned pre organized dipeptide segments studies of a 12 residue helix and β hairpin
Amino Acids, 2015Co-Authors: Siddappa Chandrappa, M Madhusudana B Reddy, Rajesh Sonti, Krishnayan Basuroy, Srinivasarao Raghothama, Padmanabhan BalaramAbstract:Secondary structure formation in oligopeptides can be induced by short nucleating segments with a high propensity to form hydrogen bonded turn conformations. Type I/III turns facilitate helical folding while type II'/I' turns favour hairpin formation. This principle is experimentally verified by studies of two designed dodecapeptides, Boc-Val-Phe-Leu-Phe-Val-Aib-Aib-Val-Phe-Leu-Phe-Val-OMe 1 and Boc-Val-Phe-Leu-Phe-Val- (D) Pro- (L) Pro-Val-Phe-Leu-Phe-Val-OMe 2. The N- and C-terminal flanking pentapeptide sequences in both cases are identical. Peptide 1 adopts a largely alpha-helical conformation in crystals, with a small 3(10) helical segment at the N-terminus. The overall helical fold is maintained in methanol solution as evidenced by NMR studies. Peptide 2 adopts an antiparallel beta-hairpin conformation stabilized by 6 interstrand hydrogen bonds. Key nuclear Overhauser effects (NOEs) provide evidence for the antiparallel beta-hairpin structure. Aromatic proton chemical shifts provide a clear distinction between the conformation of peptides 1 (helical) and 2 (beta-hairpin). The proximity of facing aromatic residues positioned at non-hydrogen bonding positions in the hairpin results in extensively ring current shifted proton resonances in peptide 2.
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designed beta hairpin peptides with defined tight turn stereochemistry
Biopolymers, 2001Co-Authors: G A Naganagowda, Isabella L Karle, Padmanabhan BalaramAbstract:The conformational analysis of two synthetic octapeptides, Boc–Leu–Val–Val–D-Pro–L-Ala–Leu–Val–Val–OMe (1) and Boc–Leu–Val–Val–D-Pro–D-Ala–Leu–Val–Val–OMe (2) has been carried out in order to investigate the effect of beta-turn stereochemistry on designed beta-hairpin structures. Five hundred megahertz 1HNMR studies establish that both peptides 1 and 2 adopt predominantly beta-hairpin conformations in methanol solution. Specific nuclear Overhauser effects provide evidence for a type II’ beta-turn conformation for the D-Pro–L-Ala segment in 1, while the NMR data suggest that the type I’ D-Pro–D-Ala b-turn conformation predominates in peptide 2. Evidence for a minor conformation in peptide 2, in slow exchange on the NMR time scale, is also presented. Interstrand registry is demonstrated in both peptides 1 and 2. The crystal structure of 1 reveals two independent molecules in the crystallographic asymmetric unit, both of which adopt beta-hairpin conformations nucleated by D-Pro–Lala type II’ beta-turns and are stabilized by three cross-strand hydrogen bonds. CD spectra for peptides and 2 show marked differences, presumably as a consequence of the superposition of spectral bands arising from both beta-turn and beta-strand conformations.
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insertion of methylene units into the turn segment of designed beta hairpin peptides
Journal of the American Chemical Society, 1999Co-Authors: Sasalu C Shankaramma, Kumar S Singh, And Aruna Sathyamurthy, Padmanabhan BalaramAbstract:The effect of insertion of methylene groups into the turn segment of beta-hairpin peptides has been investigated in the model sequence Boc-Leu-Val-Val-Dpro-delta-Ava-Leu-Val-Val-OMe. This sequence is related to the previously well-characterized model beta-hairpin octapeptide, Boc-Leu-Val-Val-DPro-Gly-Leu-Val-Val-OMe. Replacement of Gly by delta-Ava (delta-aminovaleric acid) formally corresponds to expansion of the turn segment from a two-residue loop to a three-residue loop. Backbone proton chemical shifts, vicinal coupling constants, and circular dichroism spectra for the two peptides are virtually indistinguishable. Nuclear Overhauser effects corresponding to short cross-strand interproton distances confirm that the registry of the beta-hairpin structure is maintained in the delta-Ava peptide. Restrained molecular dynamics simulations, using experimental constraints, yield two structural families that are consistent with the NOE data. Both families correspond to beta-hairpin conformations and differ only in the backbone torsion angles at the delta-Ava residue.
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beta hairpin nucleation by pro gly beta turns comparison of d pro gly and l pro gly sequences in an apolar octapeptide
Journal of The Chemical Society-perkin Transactions 1, 1998Co-Authors: Srinivasarao Raghothama, Satish Kumar Awasthi, Padmanabhan BalaramAbstract:The solution conformation of the synthetic octapeptide Boc-Leu-Val-Val-D-Pro-Gly-Leu-Val-Val-OMe 1 and Boc-Leu-Val-Val-Pro-Gly-Leu-Val-Val-OMe 2 have been investigated in organic solvents by NMR spectroscopy. Peptide 1 adopts well-defined β-hairpin conformations in CDCl3, C6D6 and (CD3)2SO, nucleated by a D-Pro-Gly Type II′ β-turn, as demonstrated by the observation of characteristic nuclear Overhauser effects (NOEs) between backbone protons and solvent shielding of NH groups involved in cross-strand hydrogen bonding. Chemical shifts and coupling constants provide further support for the β-hairpin conformation, which is consistent with the observation of a single negative circular dichroism band at 216 nm in methanol. In peptide 2, there is no characteristic interstrand NOE observed in (CD3)2SO, while in CDCl3 pronounced aggregation results in line broadening. The observation of a low temperature coefficient for the Leu(6)NH proton favours a population of Pro-Gly Type II β-turn conformations. These results suggest that in short peptide sequences, the precise nature of the β-turn is critical for hairpin formation, with Type II′ β-turns being particularly effective.
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a designed beta hairpin peptide in crystals
Proceedings of the National Academy of Sciences of the United States of America, 1996Co-Authors: Isabella L Karle, Satish Kumar Awasthi, Padmanabhan BalaramAbstract:Beta-hairpin structures have been crystallographically characterized only in very short acyclic peptides, in contrast to helices. The structure of the designed beta-hairpin, t-butoxycarbonyl-Leu-Val-Val-D-Pro-Gly-Leu-Val-Val-OMe in crystals is described. The two independent molecules of the octapeptide fold into almost ideal beta-hairpin conformations with the central D-Pro-Gly segment adopting a Type II' beta-turn conformation. The definitive characterization of a beta-hairpin has implications for de novo peptide and protein design, particularly for the development of three- and four-stranded beta-sheets.