The Experts below are selected from a list of 99 Experts worldwide ranked by ideXlab platform
Padmanabhan Balaram - One of the best experts on this subject based on the ideXlab platform.
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Pregabalin peptides: conformational comparison of γ^3- and γ^4-substituted γ-amino Acids in αγααα pentapeptides
Amino Acids, 2019Co-Authors: Krishnayan Basuroy, Kamanna Kantharaju, Subrayashastry Aravinda, Narayanaswamy Shamala, Padmanabhan BalaramAbstract:Gamma-Aminobutyric Acid (GABA, gammaAbu), an unsubstituted Gamma-Amino Acid, is an important inhibitory neurotransmitter in the mammalian brain. The role of GABA in the treatment of epilepsy has triggered a great deal of interest in substituted Gamma-Amino Acids, which may serve as GABA analogs, acting as inhibitors of GABA aminotransferase. Pregabalin (Pgn), a well-known antiepileptic drug, is also a beta-substituted gamma3-amino Acid. Pregabalin and gamma4Leu, an isomer of the pregabalin (Pgn) residue, both carrying the same isobutyryl group in the side chain, were introduced in the present study to have a comparison of their respective conformational differences as well as their role in influencing the overall conformation of the peptides, they are inserted in. Two alpha–gamma–alpha–alpha–alpha hybrid pentapeptides were designed that contain Aib-Pgn and Aib-gamma4Leu segments at the N terminus. The study provides a detailed analysis of the conformational properties and non-covalent interactions observed in the crystal structures of two polymorphs of the pentapeptide monohydrate, Boc-Aib-(S)Pgn-Leu-Phe-Val-OMe (C_38H_63N_5O_8·H_2O) and the isomeric pentapeptide, Boc-Aib-gamma4(R)Leu-Leu-Phe-Val-OMe (C_38H_63N_5O_8), obtained from single crystal X-ray diffraction experiments.
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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, Prema G Vasudev, Chandrasekharan Ramakrishnan, Narayanaswamy Shamala, Srinivasarao Raghothama, Padmanabhan 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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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, Prema G Vasudev, Chandrasekharan Ramakrishnan, Narayanaswamy Shamala, Srinivasarao Raghothama, Padmanabhan 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.
Narayanaswamy Shamala - One of the best experts on this subject based on the ideXlab platform.
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Pregabalin peptides: conformational comparison of γ^3- and γ^4-substituted γ-amino Acids in αγααα pentapeptides
Amino Acids, 2019Co-Authors: Krishnayan Basuroy, Kamanna Kantharaju, Subrayashastry Aravinda, Narayanaswamy Shamala, Padmanabhan BalaramAbstract:Gamma-Aminobutyric Acid (GABA, gammaAbu), an unsubstituted Gamma-Amino Acid, is an important inhibitory neurotransmitter in the mammalian brain. The role of GABA in the treatment of epilepsy has triggered a great deal of interest in substituted Gamma-Amino Acids, which may serve as GABA analogs, acting as inhibitors of GABA aminotransferase. Pregabalin (Pgn), a well-known antiepileptic drug, is also a beta-substituted gamma3-amino Acid. Pregabalin and gamma4Leu, an isomer of the pregabalin (Pgn) residue, both carrying the same isobutyryl group in the side chain, were introduced in the present study to have a comparison of their respective conformational differences as well as their role in influencing the overall conformation of the peptides, they are inserted in. Two alpha–gamma–alpha–alpha–alpha hybrid pentapeptides were designed that contain Aib-Pgn and Aib-gamma4Leu segments at the N terminus. The study provides a detailed analysis of the conformational properties and non-covalent interactions observed in the crystal structures of two polymorphs of the pentapeptide monohydrate, Boc-Aib-(S)Pgn-Leu-Phe-Val-OMe (C_38H_63N_5O_8·H_2O) and the isomeric pentapeptide, Boc-Aib-gamma4(R)Leu-Leu-Phe-Val-OMe (C_38H_63N_5O_8), obtained from single crystal X-ray diffraction experiments.
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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, Prema G Vasudev, Chandrasekharan Ramakrishnan, Narayanaswamy Shamala, Srinivasarao Raghothama, Padmanabhan 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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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, Prema G Vasudev, Chandrasekharan Ramakrishnan, Narayanaswamy Shamala, Srinivasarao Raghothama, Padmanabhan 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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solid state and solution conformations of a hybrid αγααγα hexapeptide characterization of a backbone expanded analog of the α polypeptide 310 helix
Biopolymers, 2008Co-Authors: Sunanda Chatterjee, Prema G Vasudev, Narayanaswamy Shamala, Srinivasarao Raghothama, P BalaramAbstract:The stereochemically constrained gamma amino Acid residue gabapentin (1-(aminomethyl)cyclohexaneacetic Acid, Gpn) has been incorporated into a host alpha-peptide sequence. The structure of a hybrid alpha gamma alpha alpha gamma alpha peptide, Boc-Leu-Gpn-Aib-Leu-Gpn-Aib-OMe in crystals reveals a continuous helical conformation stabilized by three intramolecular 4\rightarrow 1 C{12} hydrogen bonds across the alpha gamma/gamma alpha segments and one C-10 hydrogen bond across the central alpha alpha segment. This conformation corresponds to an expanded analog of the canonical all-alpha polypeptide 3(10)-helix, with insertion of two additional backbone atoms at each gamma residue. Solvent dependence of NH chemical shifts in CDCl3 solution are consistent with conformation in which the NH groups of Aib (3), Leu (4), Gpn (5), and Aib (6) are hydrogen bonded, a feature observed in the solid state. The nonsequential NOEs between Gpn (2) NH - Leu (4) NH and Gpn (2) NH Gpn (5) NH support the presence of additional conformations in solution. Temperature-dependent line broadening of NH resonances confirms the occurrence of rapid exchange between multiple conformations at room temperature. Two conformational models which rationalize the observed nonsequential NOEs tire presented, both of which contain three hydrogen bonds and ore consistent with the known stereochemical preferences of the Gpn residue.
Sunanda Chatterjee - One of the best experts on this subject based on the ideXlab platform.
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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, Prema G Vasudev, Chandrasekharan Ramakrishnan, Narayanaswamy Shamala, Srinivasarao Raghothama, Padmanabhan 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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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, Prema G Vasudev, Chandrasekharan Ramakrishnan, Narayanaswamy Shamala, Srinivasarao Raghothama, Padmanabhan 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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solid state and solution conformations of a hybrid αγααγα hexapeptide characterization of a backbone expanded analog of the α polypeptide 310 helix
Biopolymers, 2008Co-Authors: Sunanda Chatterjee, Prema G Vasudev, Narayanaswamy Shamala, Srinivasarao Raghothama, P BalaramAbstract:The stereochemically constrained gamma amino Acid residue gabapentin (1-(aminomethyl)cyclohexaneacetic Acid, Gpn) has been incorporated into a host alpha-peptide sequence. The structure of a hybrid alpha gamma alpha alpha gamma alpha peptide, Boc-Leu-Gpn-Aib-Leu-Gpn-Aib-OMe in crystals reveals a continuous helical conformation stabilized by three intramolecular 4\rightarrow 1 C{12} hydrogen bonds across the alpha gamma/gamma alpha segments and one C-10 hydrogen bond across the central alpha alpha segment. This conformation corresponds to an expanded analog of the canonical all-alpha polypeptide 3(10)-helix, with insertion of two additional backbone atoms at each gamma residue. Solvent dependence of NH chemical shifts in CDCl3 solution are consistent with conformation in which the NH groups of Aib (3), Leu (4), Gpn (5), and Aib (6) are hydrogen bonded, a feature observed in the solid state. The nonsequential NOEs between Gpn (2) NH - Leu (4) NH and Gpn (2) NH Gpn (5) NH support the presence of additional conformations in solution. Temperature-dependent line broadening of NH resonances confirms the occurrence of rapid exchange between multiple conformations at room temperature. Two conformational models which rationalize the observed nonsequential NOEs tire presented, both of which contain three hydrogen bonds and ore consistent with the known stereochemical preferences of the Gpn residue.
Prema G Vasudev - One of the best experts on this subject based on the ideXlab platform.
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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, Prema G Vasudev, Chandrasekharan Ramakrishnan, Narayanaswamy Shamala, Srinivasarao Raghothama, Padmanabhan 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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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, Prema G Vasudev, Chandrasekharan Ramakrishnan, Narayanaswamy Shamala, Srinivasarao Raghothama, Padmanabhan 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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solid state and solution conformations of a hybrid αγααγα hexapeptide characterization of a backbone expanded analog of the α polypeptide 310 helix
Biopolymers, 2008Co-Authors: Sunanda Chatterjee, Prema G Vasudev, Narayanaswamy Shamala, Srinivasarao Raghothama, P BalaramAbstract:The stereochemically constrained gamma amino Acid residue gabapentin (1-(aminomethyl)cyclohexaneacetic Acid, Gpn) has been incorporated into a host alpha-peptide sequence. The structure of a hybrid alpha gamma alpha alpha gamma alpha peptide, Boc-Leu-Gpn-Aib-Leu-Gpn-Aib-OMe in crystals reveals a continuous helical conformation stabilized by three intramolecular 4\rightarrow 1 C{12} hydrogen bonds across the alpha gamma/gamma alpha segments and one C-10 hydrogen bond across the central alpha alpha segment. This conformation corresponds to an expanded analog of the canonical all-alpha polypeptide 3(10)-helix, with insertion of two additional backbone atoms at each gamma residue. Solvent dependence of NH chemical shifts in CDCl3 solution are consistent with conformation in which the NH groups of Aib (3), Leu (4), Gpn (5), and Aib (6) are hydrogen bonded, a feature observed in the solid state. The nonsequential NOEs between Gpn (2) NH - Leu (4) NH and Gpn (2) NH Gpn (5) NH support the presence of additional conformations in solution. Temperature-dependent line broadening of NH resonances confirms the occurrence of rapid exchange between multiple conformations at room temperature. Two conformational models which rationalize the observed nonsequential NOEs tire presented, both of which contain three hydrogen bonds and ore consistent with the known stereochemical preferences of the Gpn residue.
Srinivasarao Raghothama - One of the best experts on this subject based on the ideXlab platform.
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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, Prema G Vasudev, Chandrasekharan Ramakrishnan, Narayanaswamy Shamala, Srinivasarao Raghothama, Padmanabhan 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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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, Prema G Vasudev, Chandrasekharan Ramakrishnan, Narayanaswamy Shamala, Srinivasarao Raghothama, Padmanabhan 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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solid state and solution conformations of a hybrid αγααγα hexapeptide characterization of a backbone expanded analog of the α polypeptide 310 helix
Biopolymers, 2008Co-Authors: Sunanda Chatterjee, Prema G Vasudev, Narayanaswamy Shamala, Srinivasarao Raghothama, P BalaramAbstract:The stereochemically constrained gamma amino Acid residue gabapentin (1-(aminomethyl)cyclohexaneacetic Acid, Gpn) has been incorporated into a host alpha-peptide sequence. The structure of a hybrid alpha gamma alpha alpha gamma alpha peptide, Boc-Leu-Gpn-Aib-Leu-Gpn-Aib-OMe in crystals reveals a continuous helical conformation stabilized by three intramolecular 4\rightarrow 1 C{12} hydrogen bonds across the alpha gamma/gamma alpha segments and one C-10 hydrogen bond across the central alpha alpha segment. This conformation corresponds to an expanded analog of the canonical all-alpha polypeptide 3(10)-helix, with insertion of two additional backbone atoms at each gamma residue. Solvent dependence of NH chemical shifts in CDCl3 solution are consistent with conformation in which the NH groups of Aib (3), Leu (4), Gpn (5), and Aib (6) are hydrogen bonded, a feature observed in the solid state. The nonsequential NOEs between Gpn (2) NH - Leu (4) NH and Gpn (2) NH Gpn (5) NH support the presence of additional conformations in solution. Temperature-dependent line broadening of NH resonances confirms the occurrence of rapid exchange between multiple conformations at room temperature. Two conformational models which rationalize the observed nonsequential NOEs tire presented, both of which contain three hydrogen bonds and ore consistent with the known stereochemical preferences of the Gpn residue.
