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ABSTRACT: A pair of L-leucine (L-Leu) and D-leucine (D-Leu) was incorporated into a-aminoisobutyric acid (Aib) peptide segments. Thedominant conformations of four hexapeptides, Boc-L-Leu-Aib-Aib-Aib-Aib-L-Leu-OMe (1a), Boc-D-Leu-Aib-Aib-Aib-Aib-L-Leu-OMe(1b), Boc-Aib-Aib-L-Leu-L-Leu-Aib-Aib-OMe (2a), and Boc-Aib-Aib-D-Leu-L-Leu-Aib-Aib-OMe (2b), were investigated by IR,¹H NMR, CD spectra, and X-ray crystallographic analysis. All peptides 1a,b and 2a,b formed 3₁₀-helical structures in solution. X-ray crystallographic analysis revealed that right-handed (P) 3₁₀-helices were present in 1a and 1b and a mixture of right-handed(P) and left-handed (M) 3₁₀-helices was present in 2b in their crystalline states.
Journal of Peptide Science 05/2012; 18(7):466-75. · 1.80 Impact Factor
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ABSTRACT: Chiral cyclic α,α-disubstituted amino acids, (3S,4S)- and (3R,4R)-1-amino-3,4-(dialkoxy)cyclopentanecarboxylic acids ((S,S)- and (R,R)-Ac(5)c(dOR); R: methyl, methoxymethyl), were synthesized from dimethyl L-(+)- or D-(-)-tartrate, and their homochiral homoligomers were prepared by solution-phase methods. The preferred secondary structure of the (S,S)-Ac(5)c(dOMe) hexapeptide was a left-handed (M) 3(10) helix, whereas those of the (S,S)-Ac(5)c(dOMe) octa- and decapeptides were left-handed (M) α helices, both in solution and in the crystal state. The octa- and decapeptides can be well dissolved in pure water and are more α helical in water than in 2,2,2-trifluoroethanol solution. The left-handed (M) helices of the (S,S)-Ac(5)c(dOMe) homochiral homopeptides were exclusively controlled by the side-chain chiral centers, because the cyclic amino acid (S,S)-Ac(5)c(dOMe) does not have an α-carbon chiral center but has side-chain γ-carbon chiral centers.
Chemistry 02/2012; 18(8):2430-9. · 5.93 Impact Factor
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ABSTRACT: THE TITLE PEPTIDE [SYSTEMATIC NAME: 4-(butan-2-yl)-7,20-bis-(1-hy-droxy-eth-yl)-10,23-bis-(propan-2-yl)-12,25-dithia-3,6,9,16,19,22,27,28-octa-aza-tricyclo-[22.2.1.1(11,14)]octa-cosa-1(26),11(28),13,24(27)-tetra-ene-2,5,8,15,18,21-hexone acetonitrile monosolvate], C(32)H(48)N(8)O(8)S(2)·CH(3)CN, an analogue of ascidiacyclamide (ASC) [cyclo(-Ile-Oxz-D-Val-Thz-)(2)], lies about a twofold rotation axis, so that the glycine (Gly) and isoleucine (Ile) residues are each disordered over two sites with equal occupancies. The acetonitrile mol-ecule is also located on a twofold axis passing through the C and N atoms. In the peptide, the thia-zole rings are faced to each other with a dihedral angle of 9.63 (15)° and intra-molecular N-H⋯O and O-H⋯O hydrogen bonds are observed. A bifurcated N-H⋯(O,O) hydrogen bond links the peptide mol-ecules into a layer parallel to the ab plane.
Acta Crystallographica Section E Structure Reports Online 01/2012; 68(Pt 1):o54-5. · 0.35 Impact Factor
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Chemistry 09/2011; 17(40):11107-9. · 5.93 Impact Factor
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ABSTRACT: We designed a phenylglycine (Phg)-incorporated ascidiacyclamide (ASC) analogue, cyclo(-Phg-oxazoline-d-Val-thiazole-Ile-oxazoline-d-Val-thiazole- ([Phg]ASC), with the aim of stabilizing the square conformation of ASC through interactions between amino acid side chains. X-ray diffraction analysis showed that [Phg]ASC has a square structure, similar to ASC, in which the sec-butyl group of Ile and the benzene ring of Phg are in close proximity. Consistent with that finding, ¹H NMR experiments revealed significant high-field shifts in the sec-butyl group of Ile, which suggests a potential for CH/π interactions between the sec-butyl group of Ile and the benzene ring of Phg. The CD spectra of [Phg]ASC were less affected by TFE titration or increasing temperature than those of ASC. In addition, [Phg]ASC showed approximately three times greater toxicity toward HL-60 cells than ASC. Thus the potently cytotoxic conformation of [Phg]ASC may be stabilized by CH/π interactions between the side chains of the Ile and Phg residues.
Bioorganic & medicinal chemistry 06/2011; 19(11):3372-7. · 2.82 Impact Factor
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ABSTRACT: Four types of α,α-disubstituted amino acids {i.e., α-aminoisobutyric acid (Aib), 1-aminocyclopentanecarboxylic acid (Ac(5)c), (3S,4S)-1-amino-(3,4-dimethoxy)cyclopentanecarboxylic acid [(S,S)-Ac(5)c(dOM)] and its enantiomer (R,R)-Ac(5)c(dOM)} were introduced into l-leucine-based hexapeptides and nonapeptides. The dominant conformations of eight peptides: Cbz-(L-Leu-L-Leu-dAA)(2)-OMe [dAA = 1: Aib; 2: Ac(5)c; 3: (S,S)-Ac(5)c(dOM); 4: (R,R)-Ac(5)c(dOM)] and Boc-(L-Leu-L-Leu-dAA)(3)-OMe [dAA = 5: Aib; 6: Ac(5)c; 7: (S,S)-Ac(5)c(dOM); 8: (R,R)-Ac(5)c(dOM)], were investigated by IR, CD spectra and X-ray crystallographic analysis. The CD spectra revealed that Aib hexapeptide 1 and Ac(5)c hexapeptide 2 formed right-handed (P) 3(10)-helices, while Ac(5)c(dOM) hexapeptides 3 and 4 formed a mixture of (P) 3(10)- and α-helices. The Aib nonapeptide 5 formed a (P) 3(10)-helix, the Ac(5)c nonapeptide 6 formed a mixture of (P) 3(10)- and α-helices, and the Ac(5)c(dOM) nonapeptides 7 and 8 formed (P) α-helices. X-Ray crystallographic analysis revealed that the Aib hexapeptide 1 formed a (P) 3(10)-helix, while (S,S)-Ac(5)c(dOM) hexapeptide 3 formed a (P) α-helix. In addition, the Ac(5)c nonapeptide 6 and (R,R)-Ac(5)c(dOM) nonapeptide 8 formed (P) α-helices. The Aib and achiral Ac(5)c residues have the propensity to form 3(10)-helices in short peptides, whereas the chiral Ac(5)c(dOM) residues have a penchant for forming α-helices.
Organic & Biomolecular Chemistry 03/2011; 9(9):3303-12. · 3.70 Impact Factor
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ABSTRACT: Four diastereomeric-Leu-Leu-Aib-Leu-Leu-Aib-peptides, Boc-D-Leu-L-Leu-Aib-L-Leu-L-Leu-Aib-OMe (1), Boc-L-Leu-D-Leu-Aib-L-Leu-L-Leu-Aib-OMe (2), Boc-L-Leu-L-Leu-Aib-D-Leu-L-Leu-Aib-OMe (3), and Boc-L-Leu-L-Leu-Aib-L-Leu-D-Leu-Aib-OMe (4), were synthesized. The crystals of the four hexapeptides were characterized by X-ray crystallographic analysis. Two diastereomeric hexapeptides 1 and 2 having D-Leu(1) or D-Leu(2) were folded into right-handed (P) 3(10)-helical structures, while peptide 3 having D-Leu(4) was folded into a turn structure nucleated by type III' and I' beta-turns, and peptide 4 having D-Leu(5) was folded into a left-handed (M) 3(10)-helical structure.
Journal of Peptide Science 02/2011; 17(6):420-6. · 1.80 Impact Factor
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ABSTRACT: A single chiral cyclic α,α-disubstituted amino acid, (3S,4S)-1-amino-(3,4-dimethoxy)cyclopentanecarboxylic acid [(S,S)-Ac(5)c(dOM)], was placed at the N-terminal or C-terminal positions of achiral α-aminoisobutyric acid (Aib) peptide segments. The IR and (1)H NMR spectra indicated that the dominant conformations of two peptides Cbz-[(S,S)-Ac(5)c(dOM)]-(Aib)(4)-OEt (1) and Cbz-(Aib)(4)-[(S,S)-Ac(5)c(dOM)]-OMe (2) in solution were helical structures. X-ray crystallographic analysis of 1 and 2 revealed that a left-handed (M) 3(10)-helical structure was present in 1 and that a right-handed (P) 3(10)-helical structure was present in 2 in their crystalline states.
Journal of Peptide Science 11/2010; 16(11):621-6. · 1.80 Impact Factor
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ABSTRACT: Chiral cyclic alpha-amino acid containing oligopeptide catalyzed highly enantioselective epoxidation of alpha,beta-unsaturated ketones and the alpha-helical secondary structure of the peptide catalyst were revealed by X-ray crystallographic analysis.
Organic Letters 08/2010; 12(15):3564-6. · 5.86 Impact Factor
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ABSTRACT: Three diastereomeric -Leu-Leu-Aib-Leu-Leu-Aib- peptides composed of the same numbers of L-Leu, D-Leu, and Aib residues were synthesized: Boc-L-Leu-L-Leu-Aib-D-Leu-D-Leu-Aib-OMe (1), Boc-L-Leu-D-Leu-Aib-L-Leu-D-Leu-Aib-OMe (2), and Boc-L-Leu-D-Leu-Aib-D-Leu-L-Leu-Aib-OMe (3). The crystals of the three peptides were characterized by X-ray crystallographic analysis as follows: (1) orthorhombic, P2(1)2(1)2(1), a = 21.383 A, b = 11.070 A, c = 19.560 A, Z = 4, R(1) = 0.0527, and R(w) = 0.1562; (2) monoclinic, P2(1), a = 9.391 A, b = 21.278 A, c = 11.662 A, beta = 99.125, Z = 2, R(1) = 0.0507, and R(w) = 0.1447; and (3) triclinic, P1, a = 12.545 A, b = 14.913 A, c = 15.330 A, alpha = 77.622, beta = 66.601, gamma = 78.839, Z = 2, R(1) = 0.0775, and R(w) = 0.1971. The three diastereomeric peptides, 1, 2, and 3, showed unique conformations. That is to say, 1 was folded into a left-handed (M) 3(10)-helical structure, 2 was folded into a distorted beta-hairpin nucleated by a type II' beta-turn-like structure, and 3 was folded into an S-shape turn structure based on two type II/III beta-turns.
The Journal of Organic Chemistry 08/2010; 75(15):5234-9. · 4.45 Impact Factor
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ABSTRACT: Chiral cyclic α-amino acid containing oligopeptide catalyzed highly enantioselective epoxidation of α,β-unsaturated ketones and the α-helical secondary structure of the peptide catalyst were revealed by X-ray crystallographic analysis.
07/2010;
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ABSTRACT: One chiral L-valine (L-Val) was inserted into the C-terminal position of achiral peptide segments constructed from alpha-aminoisobutyric acid (Aib) and alpha,beta-dehydrophenylalanine (Delta(Z)Phe) residues. The IR, (1)H NMR and CD spectra indicated that the dominant conformations of the pentapeptide Boc-Aib-DeltaPhe-(Aib)(2)-L-Val-NH-Bn (3) and the hexapeptide Boc-Aib-DeltaPhe-(Aib)(3)-L-Val-NH-Bn (4) in solution were both right-handed (P) 3(10)-helical structures. X-ray crystallographic analyses of 3 and 4 revealed that only a right-handed (P) 3(10)-helical structure was present in their crystalline states. The conformation of 4 was also studied by molecular-mechanics calculations.
Journal of Peptide Science 03/2010; 16(3):153-8. · 1.80 Impact Factor
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ChemInform 01/2010; 33(11).
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ABSTRACT: Protolytic equilibria of p-methoxycarbonylphenyl fluorone (PMCPF) in aqueous solutions were studied by spectrophotometry, and the species of PMCPF were determined. We describe for the first time the X-ray structure of the proton acceptor form of PMCPF.
Chemical & pharmaceutical bulletin 12/2009; 57(12):1405-8. · 1.70 Impact Factor
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ABSTRACT: Two series of homooligomers composed of diastereoisomeric cyclic alpha-amino acids having two chiral centers at the alpha-carbon and the side chain were synthesized, and their preferred secondary structures were studied in solution and in the crystal state. The oligomers are a new class of helical-foldamers possessing two kinds of chiral centers on the helical backbone and at the lateral surface of the helix.
Organic Letters 03/2009; 11(5):1135-7. · 5.86 Impact Factor
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ABSTRACT: The crystal of the Leu-enkephalin raceinate (L-Tyr-Gly-Gly-L-Phe-L-Leu and d-Tyr-Gly-Gly-D-Phe-D-Leu) was obtained as a centrosymmetric space group. Crystal data: C28H37N5O7· 1.5H2O, Mw, = 582.6, triclinic, space group PI, a = 11.176(3), b = 16.115(3), c = 10.204(4) Å, α= 92.41(3), β= 104.86(2), γ= 85.35(2) °, V= 1770(1) Å3, Z= 2; F(000) = 640, μ(CuKα) = 6.50 cm−1, Dx= 1.081 g cm−3. The structure was determined by X-ray diffraction. The conformation of the Leu-enkephalin racemate was classified into the extended form which has been often observed in natural enkephalin. The symmetry-related molecules were connected by hydrogen bonds and arranged in an antiparallel fashion. The molecular packing showed a sheet structure similar to that of natural enkephalin.
European Journal of Allergy and Clinical Immunology 01/2009; 43(4):325 - 331. · 1.30 Impact Factor
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ABSTRACT: Methods for the fluorophotometric determination of hydrogen peroxide (H(2)O(2)) and other reactive oxygen species (ROS) were proposed by using the fluorescence reaction between H(2)O(2) or other ROS and fluorescein hydrazide (FH). In the determination of H(2)O(2), the calibration curve exhibited linearity over the H(2)O(2) concentration range of 2.1-460 ng ml(-1) at an emission wavelength of 527 nm with an excitation of 460 nm and with the relative standard deviations (n=6) of 4.06%, 1.78%, and 2.21% for 3.1 ng ml(-1), 30.8 ng ml(-1), and for 308 ng ml(-1) of H(2)O(2), respectively. The detection limit for H(2)O(2) was 0.7 ng ml(-1) due to three blank determinations (rho=3). The calibration curves for ROS-related compounds were also constructed under the optimum conditions. This method was successfully applied in the assay of H(2)O(2) in human urine. In addition, we performed the characterization of FH, and interesting information was obtained with regard to the relationship between the chemical structure and fluorescence.
CHEMICAL & PHARMACEUTICAL BULLETIN 08/2008; 56(7):977-81. · 1.59 Impact Factor
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Shinichiro Kamino,
Hayato Ichikawa,
Shun-ichi Wada,
Yuka Horio,
Yoshihide Usami,
Takako Yamaguchi,
Toshiki Koda,
Aki Harada,
Kazusa Shimanuki,
Masao Arimoto, Mitsunobu Doi,
Yoshikazu Fujita
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ABSTRACT: We have demonstrated the synthesis of regioisomerically pure unsymmetrical xanthene derivatives consisting of three units which can be independently modified to control their physical properties. The photochemical properties of the synthetic unsymmetrical xanthene derivatives were investigated in solution by UV-vis absorption and fluorescence measurements, and their cell imaging properties were examined by confocal laser-scanning microscopy.
Bioorganic & medicinal chemistry letters 07/2008; 18(15):4380-4. · 2.65 Impact Factor
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ABSTRACT: Pericosines A-E 1-5 have been isolated from a strain of Periconia byssoides originally separated from the sea hare Aplysia kurodai. Among them, pericosines C 3 and E 5 were separated as enantiomeric mixtures. Their stereostructures, except for compound 1, have been elucidated or identified on the basis of spectroscopic analyses, including 1D and 2D NMR techniques, and X-ray analysis. In addition, conformation for all the compounds has been discussed. Compounds 1-3 exhibited significant growth inhibition against tumour cell lines. Pericosine A 1 also showed significant in vivo tumour inhibitory activity. In addition, compound inhibited the protein kinase EGFR and topoisomerase II.
Organic & Biomolecular Chemistry 01/2008; 5(24):3979-86. · 3.70 Impact Factor
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ABSTRACT: The conformation of the title tripeptide methyl ester hydro-chloride monohydrate, 1-[2-(methoxycarbonylmethylaminocarbonyl)pyrrolidin-1-ylcarbonyl]-2-phenylethanaminium chloride monohydrate, C(17)H(24)N(3)O(4) (+)·Cl(-)·H(2)O, is extended, but the structure cannot be classified as any typical secondary structure. Interactions through water molecules and chloride ions were formed, in addition to peptide-peptide hydrogen bonds, stabilizing the molecular packing. In comparison with the previous β-turn structure of the Phe-d-Pro-Gly analogue [Doi, Ichimiya & Asano (2007 ▶). Acta Cryst. E63, o4691], it was suggested that the difference between the chiralities of Phe and Pro residues of the title compound is important to induce the β-turn structure.
Acta Crystallographica Section E Structure Reports Online 01/2008; 64(Pt 4):o704. · 0.35 Impact Factor
