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P 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, Srinivasarao Raghothama, M Madhusudana B Reddy, Rajesh Sonti, Krishnayan Basuroy, P 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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expanding the peptide Beta turn in alpha gamma hybrid sequences 12 atom hydrogen bonded helical and Hairpin turns
Journal of the American Chemical Society, 2009Co-Authors: Sunanda Chatterjee, Srinivasarao Raghothama, Narayanaswamy Shamala, Prema G Vasudev, Chandrasekharan Ramakrishnan, P BalaramAbstract:Hybrid peptide segments containing contiguous alpha and gamma amino acid residues can form C-12 hydrogen bonded turns which may be considered as backbone expanded analogues of C-10 Beta-turns) found in alpha alpha segments. Exploration of the regular hydrogen bonded conformations accessible for hybrid alpha gamma sequences is facilitated by the use of a stereochemically constrained gamma amino acid residue gabapentin (1-aminomethylcyclohexaneacetic acid, Gpn), in which the two torsion angles about C-gamma-C-Beta (theta(1)) and C-Beta-C-alpha (theta(2)) are predominantly restricted to gauche conformations. The crystal structures of the octapeptides Boc-Gpn-Aib-Gpn-Aib-Gpn-Aib-Gpn-Aib-OMe (1) and Boc-Leu-Phe-Val-Aib-Gpn-Leu-Phe-Val-OMe (2) reveal two distinct conformations for the Aib-Gpn segment. Peptide 1 forms a continuous helix over the Aib(2)-Aib(6) segment, while the peptide 2 forms Beta-Hairpin structure stabilized by four cross-strand hydrogen bonds with the Aib-Gpn segment forming a nonhelical C-12 turn. The robustness of the helix in peptide 1 in solution is demonstrated by NMR methods. Peptide 2 is conformationally fragile in solution with evidence of Beta-Hairpin conformations being obtained in methanol. Theoretical calculations permit delineation of the various C-12 hydrogen bonded structures which are energetically feasible in alpha gamma and gamma alpha sequences.
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infinite pleated Beta sheet formed by the Beta Hairpin boc Beta phe Beta phe d pro gly Beta phe Beta phe ome
Proceedings of the National Academy of Sciences of the United States of America, 2002Co-Authors: Isabella L Karle, Hosahudya N Gopi, P BalaramAbstract:A Beta-Hairpin conformation and extended Beta-pleated sheet assembly have been characterized by single crystal x-ray diffraction for the synthetic peptide t-butoxycarbonyl-Beta-Phe-Beta-Phe-D-Pro-Gly-b-Phe-b-Phe-methyl ester [b-Phe: (S)-b3 homophenylalanine]. The centrally located D-Pro-Gly segment nucleates a chain reversal in a type II’ Beta-turn conformation. Two intramolecular cross-strand hydrogen bonds stabilize the peptide fold. Intermolecular NH…O=C hydrogen bonds (two on each side of the Hairpin) connect the Hairpins into an infinitely extended Beta-sheet. The Beta-residues cause all CAOgroups to point in the same direction, resulting in a ‘‘polar’’ sheet by the unidirectional alignment of NH…O=C hydrogen bonds. In contrast, Beta-sheets formed by Beta-residues have alternating directions for the hydrogen bonds, thus resulting in an ‘‘apolar’’ sheet. The crystallographic parameters for C53H66N6O9.CH3OH are: space group P21, a = 9.854(2) A, b = 10.643(2) A, c = 25.296(4) A, Beta = 100.39(2)°, Z = 2, agreement factor R1 _ 0.065 for 3,706 data observed >4_(F) and a resolution of 0.90 A.
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peptide hybrids containing alpha and Beta amino acids structure of a decapeptide Beta Hairpin with two facing Beta phenylalanine residues
Proceedings of the National Academy of Sciences of the United States of America, 2001Co-Authors: Isabella L Karle, Hosahudya N Gopi, P BalaramAbstract:A Beta-Hairpin conformation has been characterized in crystals of the decapeptide t-butoxycarbonyl-Leu-Val-BetaPhe-Val-DPro-Gly-Leub Phe-Val-Val-methyl ester [bPhe; (S)-b3 homophenylalanine] by x-ray diffraction. The polypeptide chain reversal is nucleated by the centrally positioned DPro-Gly segment, which adopts a type-I’ Beta-turn conformation. Four intramolecular cross-strand hydrogen bonds stabilize the peptide fold. The BetaPhe(3) and BetaPhe(8) residues occupy facing positions on the Hairpin, with the side chains projecting on opposite faces of the Beta-sheet. At the site of insertion of Beta- residues, the polarity of the peptide units along each strand reverses, as compared with the alpha-peptide segments. In this analog, a small segment of a polar sheet is observed, where adjacent CO and NH groups line up in opposite directions in each strand. In the crystal, an extended Beta-sheet is formed by hydrogen bonding between strands of antiparallel pairs of Beta-Hairpins. The crystallographic parameters for C65H102N10O13z 3H2O are: space group P212121; a 5 19.059(8) A, b 5 19.470(2) A, c 5 21.077(2) A; Z 5 4; agreement factor R1 5 9.12% for 3,984 data observed >4s(F) and a resolution of 0.90 A.
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designed Beta Hairpin peptides with defined tight turn stereochemistry
Biopolymers, 2001Co-Authors: G A Naganagowda, Isabella L Karle, P 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.
Srinivasarao Raghothama - One of the best experts on this subject based on the ideXlab platform.
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Conformations of heterochiral and homochiral proline-pseudoproline segments in peptides: context dependent cis-trans peptide bond isomerization.
Biopolymers, 2020Co-Authors: Kantharaju, Srinivasarao Raghothama, Upadhyayula Surya Raghavender, Subrayashastry Aravinda, Narayanaswamy Shamala, Padmanabhan BalaramAbstract:The pseudoproline residue (Psi Pro, L-2,2-dimethyl-1,3-thiazolidine-4-carboxylic acid) has been introduced into heterochiral diproline segments that have been previously shown to facilitate the formation of Beta-Hairpins, containing central two and three residue turns. NMR studies of the octapeptide Boc-Leu-Phe-Val-(D)Pro-Psi Pro-Leu-Phe-Val-OMe (1), Boc-Leu-Val-Val-(D)Pro-Psi Pro-Leu-Val-Val-OMe (2), and the nonapeptide sequence Boc-Leu-Phe-Val-(D)Pro-Psi Pro-(D)Ala-Leu-Phe-Val-OMe (3) established well-registered Beta-Hairpin structures in chloroform solution, with the almost exclusive population of the trans conformation for the peptide bond preceding the Psi Pro residue. The Beta-Hairpin conformation of 1 is confirmed by single crystal X-ray diffraction. Truncation of the strand length in Boc-Val-(D)Pro-Psi Pro-Leu-OMe (4) results in air increase in the population of the cis conformer, with a cis/trans ratio of 3.65. Replacement of Psi Pro in 4 by (L)Pro in 5, results in almost exclusive population of the trans form, resulting in an incipient Beta-Hairpin conformation, stabilized by two intramolecular hydrogen bonds. Further truncation of the sequence gives an appreciable rise in the population of cis conformers in the tripeptide piv-(D)Pro-Psi Pro-Leu-OMe (6). In the homochiral segment Piv-Pro Psi Pro-Leu-OMe (7) only the cis form is observed with the NMR evidence strongly supporting a type VIa Beta-turn conformation, stabilized by a 4 -> 1 hydrogen bond between the Piv (CO) and Leu (3) NH groups. The crystal structure of the analog peptide 7a (Piv-Pro-Psi(H,CH3)Pro-Leu-NHMe) confirms the cis peptide bond geometry for the Pro-Psi(H,CH3)pro peptide bond, resulting in a type VIa Beta-turn conformation.
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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, Srinivasarao Raghothama, M Madhusudana B Reddy, Rajesh Sonti, Krishnayan Basuroy, P 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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expanding the peptide Beta turn in alpha gamma hybrid sequences 12 atom hydrogen bonded helical and Hairpin turns
Journal of the American Chemical Society, 2009Co-Authors: Sunanda Chatterjee, Srinivasarao Raghothama, Narayanaswamy Shamala, Prema G Vasudev, Chandrasekharan Ramakrishnan, P BalaramAbstract:Hybrid peptide segments containing contiguous alpha and gamma amino acid residues can form C-12 hydrogen bonded turns which may be considered as backbone expanded analogues of C-10 Beta-turns) found in alpha alpha segments. Exploration of the regular hydrogen bonded conformations accessible for hybrid alpha gamma sequences is facilitated by the use of a stereochemically constrained gamma amino acid residue gabapentin (1-aminomethylcyclohexaneacetic acid, Gpn), in which the two torsion angles about C-gamma-C-Beta (theta(1)) and C-Beta-C-alpha (theta(2)) are predominantly restricted to gauche conformations. The crystal structures of the octapeptides Boc-Gpn-Aib-Gpn-Aib-Gpn-Aib-Gpn-Aib-OMe (1) and Boc-Leu-Phe-Val-Aib-Gpn-Leu-Phe-Val-OMe (2) reveal two distinct conformations for the Aib-Gpn segment. Peptide 1 forms a continuous helix over the Aib(2)-Aib(6) segment, while the peptide 2 forms Beta-Hairpin structure stabilized by four cross-strand hydrogen bonds with the Aib-Gpn segment forming a nonhelical C-12 turn. The robustness of the helix in peptide 1 in solution is demonstrated by NMR methods. Peptide 2 is conformationally fragile in solution with evidence of Beta-Hairpin conformations being obtained in methanol. Theoretical calculations permit delineation of the various C-12 hydrogen bonded structures which are energetically feasible in alpha gamma and gamma alpha sequences.
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Design of a peptide Hairpin containing a central three-residue loop.
Journal of the American Chemical Society, 2006Co-Authors: Srinivasarao Raghothama, Padmanabhan BalaramAbstract:The construction of a designed $\Beta$-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 $\Beta$-Hairpin $Boc-Leu-Phe-Val-^DPro-^LPro-Leu-Phe-Val-OMe$ (1). Characterization of the registered $\Beta$-Hairpins in peptides 1 and 2 is based on the observation of key nuclear Overhauser effects (NOEs) in $CDCl_3$ and $CD_3OH$. 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 $5\rightarrow1$ hydrogen bond between Val3 CO and Leu7 NH groups $(C_{13}, \alpha-turn)$ and a $3\rightarrow1$ hydrogen bond between $^DPro4$ CO and $^DAla6$ NH groups $(C_7, \gamma-turn)$. NMR derived structures suggest that in peptide 2, $^DAla(6)$ adopts an $\alpha_L$ conformation. In peptide 1, the $^DPro-^LPro$ segment adopts a type II' $\Beta$-turn. Replacement of $^DAla (6)$ in peptide 2 by $^LAla$ in peptide 3 yields a $\Beta$-Hairpin conformation, with a central $^DPro-^LPro$ two-residue loop. Strand slippage at the C-terminus results in altered registry of the antiparallel strands.
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A four stranded Beta-sheet structure in a designed, synthetic polypeptide
Chemical Communications, 1999Co-Authors: Srinivasarao Raghothama, Padmanabhan BalaramAbstract:A designed four stranded Beta-sheet peptide has been constructed using three internal d-proline residues to nucleate Beta-Hairpin formation.
Yukio Sugiura - One of the best experts on this subject based on the ideXlab platform.
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swapping of the Beta Hairpin region between sp1 and gli zinc fingers significant role of the Beta Hairpin region in dna binding properties of c2h2 type zinc finger peptides
Biochemistry, 2005Co-Authors: Yasuhisa Shiraishi, Miki Imanishi, Tatsuya Morisaki, Yukio SugiuraAbstract:: The recent design strategy of zinc finger peptides has mainly focused on the alpha-helix region, which plays a direct role in DNA recognition. On the other hand, the study of non-DNA-contacting regions is extremely scarce. By swapping the Beta-Hairpin regions between the Sp1 and GLI zinc fingers, in this study, we investigated how the Beta-Hairpin region of the C(2)H(2)-type zinc finger peptides contributes to the DNA binding properties. Surprisingly, the Sp1 mutant with the GLI-type Beta-Hairpin had a higher DNA binding affinity than that of the wild-type Sp1. The result of the DNase I footprinting analyses also showed the change in the DNA binding pattern. In contrast, the GLI zinc finger completely lost DNA binding ability as a result of exchanging the Beta-Hairpin region. These results strongly indicate that the Beta-Hairpin region appears to function as a scaffold and has an important effect on the DNA binding properties of the C(2)H(2)-type zinc finger peptides.
Marcey L Waters - One of the best experts on this subject based on the ideXlab platform.
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Cross-strand histidine–aromatic interactions enhance acyl-transfer rates in Beta-Hairpin peptide catalysts
Organic and Biomolecular Chemistry, 2014Co-Authors: Masaomi Matsumoto, Michel R Gagne, Marcey L WatersAbstract:A reactive tagging methodology was used to select the species most reactive to an acylation reagent from a solid phase library of Beta Hairpin peptides. Hits bearing an electron-rich aromatic residue across strand from a reactive histidine were found to competitively become N-acylated. In addition to displaying rapid N-acylation rates the hit peptide was additionally deacylated in the presence of a nucleophile, thus closing a putative catalytic cycle. Variants of the hit peptide were studied to elucidate both the magnitude (up to 18 000-fold over background, kcat/kuncat = 94 000 000, or 45-fold over Boc-histidine methyl ester) and mechanism of acyl transfer catalysis. A combination of CH–π, cation–π and HisH+–O interactions in the cationic imidazole transition state is implicated in the rate acceleration, in addition to the fidelity of the Beta Hairpin fold. Moreover, NMR structural data on key intermediates or models thereof suggest that a key feature of this catalyst is the ability to access several different stabilizing conformations along the catalysis reaction coordinate.
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cross strand histidine aromatic interactions enhance acyl transfer rates in Beta Hairpin peptide catalysts
Organic and Biomolecular Chemistry, 2014Co-Authors: Masaomi Matsumoto, Michel R Gagne, Marcey L WatersAbstract:A reactive tagging methodology was used to select the species most reactive to an acylation reagent from a solid phase library of Beta Hairpin peptides. Hits bearing an electron-rich aromatic residue across strand from a reactive histidine were found to competitively become N-acylated. In addition to displaying rapid N-acylation rates the hit peptide was additionally deacylated in the presence of a nucleophile, thus closing a putative catalytic cycle. Variants of the hit peptide were studied to elucidate both the magnitude (up to 18 000-fold over background, kcat/kuncat = 94 000 000, or 45-fold over Boc-histidine methyl ester) and mechanism of acyl transfer catalysis. A combination of CH–π, cation–π and HisH+–O interactions in the cationic imidazole transition state is implicated in the rate acceleration, in addition to the fidelity of the Beta Hairpin fold. Moreover, NMR structural data on key intermediates or models thereof suggest that a key feature of this catalyst is the ability to access several different stabilizing conformations along the catalysis reaction coordinate.
Wonpil Im - One of the best experts on this subject based on the ideXlab platform.
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Beta Hairpin restraint potentials for calculations of potentials of mean force as a function of Beta Hairpin tilt rotation and distance
Journal of Computational Chemistry, 2009Co-Authors: Wonpil ImAbstract:We have developed a set of restraint potentials for β-Hairpin tilt relative to the membrane normal, β-Hairpin rotation around the β-Hairpin axis, and Hairpin–Hairpin distance. Such restraint potentials enable us to characterize the molecular basis of specific β-Hairpin tilt and rotation in membranes and Hairpin–Hairpin interactions at the atomic level by sampling their conformational space along these degrees of freedom, i.e., reaction coordinates, during molecular dynamics simulations. We illustrate the efficacy of the β-Hairpin restraint potentials by calculating the potentials of mean force (PMFs) as a function of tilt and rotation angles of protegrin-1 (PG-1), a β-Hairpin antimicrobial peptide, in an implicit membrane model. The peptide association in the membrane is also examined by calculating the PMFs as a function of distance between two PG-1 peptides in various dimer interfaces. These novel restraint potentials are found to perform well in each of these cases and are expected to be a useful means to study the microscopic driving forces of insertion, tilting, and rotation of β-Hairpin peptides in membranes as well as their association in aqueous solvent or membrane environments particularly when combined with explicit solvent models. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009
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Beta‐Hairpin restraint potentials for calculations of potentials of mean force as a function of Beta‐Hairpin tilt, rotation, and distance
Journal of Computational Chemistry, 2009Co-Authors: Wonpil ImAbstract:We have developed a set of restraint potentials for β-Hairpin tilt relative to the membrane normal, β-Hairpin rotation around the β-Hairpin axis, and Hairpin–Hairpin distance. Such restraint potentials enable us to characterize the molecular basis of specific β-Hairpin tilt and rotation in membranes and Hairpin–Hairpin interactions at the atomic level by sampling their conformational space along these degrees of freedom, i.e., reaction coordinates, during molecular dynamics simulations. We illustrate the efficacy of the β-Hairpin restraint potentials by calculating the potentials of mean force (PMFs) as a function of tilt and rotation angles of protegrin-1 (PG-1), a β-Hairpin antimicrobial peptide, in an implicit membrane model. The peptide association in the membrane is also examined by calculating the PMFs as a function of distance between two PG-1 peptides in various dimer interfaces. These novel restraint potentials are found to perform well in each of these cases and are expected to be a useful means to study the microscopic driving forces of insertion, tilting, and rotation of β-Hairpin peptides in membranes as well as their association in aqueous solvent or membrane environments particularly when combined with explicit solvent models. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009
