- Selective Monovalent Galectin-8 Ligands Based on 3-Lactoylgalactoside
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Galectin-8 has gained attention as a potential new pharmacological target for the treatment of various diseases, including cancer, inflammation, and disorders associated with bone mass reduction. To that end, new molecular probes are needed in order to better understand its role and its functions. Herein we aimed to improve the affinity and target selectivity of a recently published galectin-8 ligand, 3-O-[1-carboxyethyl]-β-d-galactopyranoside, by introducing modifications at positions 1 and 3 of the galactose. Affinity data measured by fluorescence polarization show that the most potent compound reached a KD of 12 μM. Furthermore, reasonable selectivity versus other galectins was achieved, making the highlighted compound a promising lead for the development of new selective and potent ligands for galectin-8 as molecular probes to examine the protein's role in cell-based and in vivo studies.
- Anderluh, Marko,Girardi, Benedetta,Leffler, Hakon,Manna, Martina,Mravljak, Janez,Nilsson, Ulf J.,Ricklin, Daniel,Schwardt, Oliver,Van Klaveren, Sjors,Jakopin, ?iga,Toma?i?, Tihomir
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supporting information
(2021/10/08)
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- ENDOPARASITIC DEPSIPEPTIDES
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The present invention provides cyclic depsipeptides of Formula (1), stereoisomers thereof, and veterinary acceptable salts thereof (1) wherein each of R1, R2, R3, R4, L1, and L2, are as defined herein. The present invention also contemplates compositions and methods of treatment as an endoparasiticide with a Formula (1) compound.
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Page/Page column 56; 59; 60
(2019/06/17)
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- ENDOPARASITIC DEPSIPEPTIDES
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The present invention provides cyclic depsipeptides of Formula (1), stereoisomers thereof, and veterinary acceptable salts thereof wherein each of R1, R2, R3, R4, L1, and L2 are as defined herein. The present invention also contemplates compositions, methods of treatment, and uses as a medicament to treat an animal for an endoparasitic infection with a Formula (1 ) compound.
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Page/Page column 44; 48
(2019/11/28)
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- An effective cis-β-octahedral Mn(iii) SALPN catalyst for the Mukaiyama-Isayama hydration of α,β-unsaturated esters
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Two cis-β-MnIIISALPN catalysts were synthesised and tested in the Mukaiyama-Isayama hydration of α,β-unsaturated esters. The MnIIIEtOSALPN(acac) complex 7 is the most active and catalyses hydration with little or no detectable undesired alkene reduction. This catalyst is superior for alkene hydration compared to the originally reported Mn(dpm)3 catalyst.
- Donnelly, Paul S.,North, Andrea J.,Radjah, Natalia Caren,Ricca, Michael,Robertson, Angus,White, Jonathan M.,Rizzacasa, Mark A.
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supporting information
p. 7699 - 7702
(2019/07/09)
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- Total synthesis of the cyclic depsipeptide YM-280193, a platelet aggregation inhibitor
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The first total synthesis of YM-280193, a cyclic depsipeptide that inhibits the ADP-induced aggregation of human platelets, is described. The monomer and dipeptide fragments were prepared using conventional chemistry and subsequently assembled by Fmoc-solid-phase peptide synthesis (Fmoc-SPPS). A late-stage novel bis-alkylation-elimination of cysteine on-resin was employed to introduce the unnatural N-methyldehydroalanine moiety. The final step involved execution of a key macrolactamization reaction between the hindered unnatural N,O-dimethylthreonine and ?2-hydroxyleucine residues.
- Kaur, Harveen,Harris, Paul W. R.,Little, Peter J.,Brimble, Margaret A.
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supporting information
p. 492 - 495
(2015/03/05)
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- Organocatalytic synthesis of optically active aryllactic acid derivatives from β-ketosulfoxides
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The organocatalytic synthesis of new α-acyloxy-3-arylpropionic thioesters has been accomplished providing some enantioenriched important aryllactic acid derivatives in good yield and enantioselectivities.
- Capitta, Francesca,Melis, Nicola,Secci, Francesco,Romanazzi, Giuseppe,Frongia, Angelo
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p. 649 - 660
(2015/10/19)
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- Chemoselective esterification of α-hydroxyacids catalyzed by salicylaldehyde through induced intramolecularity
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A new, direct and chemoselective esterification of α-hydroxyacids was developed using a reversible covalent-binding strategy. By taking advantage of acetal chemistry, simple aldehydes can be used to efficiently catalyze the esterification of α-hydroxy carboxylic acids in the presence of β-hydroxyacid moieties or other carboxylic acids in amounts equal to or in excess of the alcohols. A diverse array of α-aryl, α-alkyl, α-heteroaryl, and functionalized α-hydroxyacids were smoothly esterified with 1° and 2° alcohols catalyzed by 10 mol% inexpensive and commercially available salicylaldehyde, furnishing the resultant esterification products in 83-95% yields after a simple basic aqueous workup to remove the unreacted hydroxyacids. In addition, the salicylaldehyde can be recovered through vacuum distillation or silica gel purification, thereby meeting the standards of green chemistry. A mechanistic study proved that the formation of covalent adduct III during our proposed catalytic cycle (Scheme 1A) is responsible for the real catalysis.
- Weng, Shiue-Shien,Li, Hsin-Chun,Yang, Teng-Mao
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p. 1976 - 1986
(2013/03/13)
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- Synthesis, characterization and activity of new phosphonate dipeptides as potential inhibitors of VanX
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VanX, a Zn(II)-dependent D-ala-D-ala dipeptidase, is essential for vancomycin resistance in Enterococcus faecium. The enzymatic activity of VanX was previously found to be inhibited competitively by 2-{[(1-aminoethyl) (hydroxy) phosphoryl]oxy} propanoic acid (1B). Here we report the synthesis and characterization of seven phosphonate dipeptide analogs of D-ala-D-ala with various substituent, the activity evaluation indicated that six of these phosphonate analogs inhibit VanX with IC50 of 0.48-8.21 mM. These data revealed a structure-activity relationship which is that the large substituent group on β-carbon resulted in low binding affinity of the phonphonate analog to VanX. This information will be helpful to guide the design and synthesis of the tightly-binding inhibitors for VanX.
- Jia, Chao,Yang, Ke-Wu,Liu, Cheng-Cheng,Feng, Lei,Xiao, Jian-Min,Zhou, Li-Sheng,Zhang, Yi-Lin
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p. 482 - 484
(2012/03/11)
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- Characterization of binding affinities in a chromatographic system by suspended state HR/MAS NMR spectroscopy
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In the current work a racemate of (R)-and (S)-benzylmandelate was separated with a stereoselective polysaccharide-based chiral stationary phase by HPLC. To elucidate the occurring chiral molecular recognition processes in the heterogeneous system used, NMR spectroscopy was chosen under high resolution/magic angle spinning (HR/MAS) NMR conditions in the suspended state. Therefore, and as a proof of concept, a combination of several NMR methods such as spin - lattice relaxation time (T1) measurements (T1), the saturation transfer difference, and the 2D experiment of the transferred nuclear overhauser enhancement spectroscopy technique were applied. With HR/MAS NMR it is feasible to combine NMR and chromatography to achieve further insights into the separation process. Copyright
- Friebolin, Volker,Marten, Silvia,Albert, Klaus
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experimental part
p. 111 - 116
(2010/09/18)
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- 6, 11-bridged tricyclic macrolides
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The present invention discloses compounds of formula I, or pharmaceutically acceptable salts, esters, or prodrugs thereof: which exhibit antibacterial properties. The present invention further relates to pharmaceutical compositions comprising the aforemen
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Page/Page column 28-29
(2008/06/13)
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- Total synthesis of hirsutellide A
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The total synthesis of hirsutellide A 1 was described. The linear hexadepsipeptide precursor 2 was synthesized in 45% yield from N-Boc-Me-Gly by three coupling reactions with DCC, HATU and BOP-Cl, respectively. Macrocyclization was successfully performed on the fully deprotected amino acid 14 with BOP-Cl in 15% yield and with FDDP in 22% yield.
- Xu, Yanjie,Chen, Ligong,Duan, Xuemin,Meng, Yi,Jiang, Liqin,Li, Meiling,Zhao, Guangle,Li, Yang
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p. 4377 - 4379
(2007/10/03)
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- Synthesis of the key precursor of Hirsutellide A
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Hexadepsipeptide 2, the precursor of Hirsutellide A (1), was synthesized in an overall yield of 45% from N-Boc-Me-Gly via three coupling reactions using dicyclohexylcarbodiimide (DCC), O-(7-azabenzotriazol-1-yl)-N,N,N′, N′-tetramethyluronium hexafluorophosphate (HATU) and bis(2-oxo-3- oxazolidinyl)phosphinic chloride (BOP-Cl), respectively.
- Xu, Yanjie,Duan, Xuemin,Li, Meiling,Jiang, Liqin,Zhao, Guangle,Meng, Yi,Chen, Ligong
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p. 259 - 264
(2007/10/03)
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- Synthesis of brassinosteroids of varying acyl side chains and evaluation of their brassinolide-like activity
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Brassinosteroids containing various side chain moieties were synthesized and their activity was determined as the reciprocal logarithm of the ED 50 (50% effective dose per plant in moles) in the rice lamina inclination assay using synergist indole-3-acetic acid (IAA). The introduction of a hydroxyl group in the α-position to the carbonyl group of the ester structure significantly enhanced the activity. 2α,3α-Dihydroxy- 17β-[(2R,3S)-2-hydroxy-3-methylpentanoyl]oxy-B-homo-7-oxa-5α- androstan-6-one showed the highest activity, for which the pED50 was determined to be 10.5 under synergistic conditions with IAA. Under identical conditions, the pED50 values of brassinolide and castasterone were determined to be 13.6 and 12.3 respectively. With respect to the α-carbon of the acyl moiety, the R-form was 10 times more potent than the corresponding S-form. Substituting the terminal structure (Et) of the side chain to that of the most potent compound, brassinolide (i-Pr), did not increase the activity.
- Uesusuki, Shinya,Watanabe, Bunta,Yamamoto, Shuji,Otsuki, Junko,Nakagawa, Yoshiaki,Miyagawa, Hisashi
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p. 1097 - 1105
(2007/10/03)
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- Expanding the utility of proteases in synthesis: Broadening the substrate acceptance in non-coded amide bond formation using chemically modified mutants of subtilisin
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The strategy of combined site directed mutagenesis and chemical modification creates chemically modified mutants (CMMs) with greatly broadened substrate specificities. We have previously reported that the CMMs of subtilisin Bacillus lentus (SBL) are efficient catalysts for the coupling of both L- and D-amino acids. We now report that these powerful catalysts also allow amide bond formation between a variety of non-coded carboxylic acids, including β-alanine and β-amino homologues of phenylalanine, with both L- and D-amino acid nucleophiles. As a guide to enzyme efficiency, a hydrolysis assay indicating pH change has been employed. CMMs selected by this screen furnished higher yields of coupling products compared to the wild-type enzyme (WT). Furthermore, both WT and CMM enzymes allow highly stereoselective aminolysis of a meso diester with an amino acid amine. These results highlight the utility of CMMs in the efficient formation of non-coded amides as potential peptide isosteres.
- Khumtaveeporn, Kanjai,Ullmann, Astrid,Matsumoto, Kazutsugu,Davis, Benjamin G.,Jones
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p. 249 - 261
(2007/10/03)
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- Design of mechanism-based carboxypeptidase A inactivators on the basis of the X-ray crystal structure and catalytic reaction pathway
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The X-ray crystal structure of the complex of carboxypeptidase A (CPA) and Gly-Tyr, has been documented. The crystal structure reveals that both the amide carbonyl oxygen and the terminal amino nitrogen of Gly-Tyr coordinate to the active site zinc ion of CPA in a bidentate fashion, whereby the zinc-bound water molecule is displaced by the amino group. As to the catalytic mechanism of CPA, it is generally believed that while in the cases of ester substrates the carboxylate of Glu-270 functions as the nucleophile which attacks the scissile carbonyl carbon (anhydride pathway), in the case of peptide substrates the zinc-bound water molecule attacks the scissile peptide bond (general base pathway). In light of the X-ray crystal structure and the proposed catalytic mechanism for the enzyme, it is envisioned that the ester bond of O-(hydroxyacetyl)-l-β-phenyllactic acid (l-1) would be hydrolyzed by the attack of the carboxylate of Glu-270 to generate an anhydride intermediate. The latter intermediate would then undergo an intramolecular rearrangement initiated by the attack of the hydroxyl to result in to form an ester bond with the Glu-270 carboxylate. This ester formation impairs the catalytic activity of CPA. We have demonstrated using kinetic analysis that l-1 is indeed an inactivator for the enzyme having the k(inact)/K(I) value of 0.057M-1s-1. We have also demonstrated that N-(hydroxyacetyl)-l-phenylalanine (l-2) inactivates the enzyme with the k(inact)/K(I) value of 0.071M-1s-1, suggesting that the carboxylate becomes to attack the peptide carbonyl carbon to generate the same anhydride intermediate as that formed in the inactivation of CPA by l-1. The formation of the anhydride intermediate rather than a tetrahedral transition state that is expected for peptide type substrates was envisioned to occur on the ground that the zinc-bound water molecule is displaced by the hydroxyl of l-2 upon binding to the enzyme. Copyright (C) 1998 Elsevier Science Ltd.
- Lee, Kyung Joo,Kim, Dong H.
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p. 1613 - 1622
(2007/10/03)
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- Building Units for N-Backbone Cyclic Peptides. 3. Synthesis of Protected Nα-(ω-Aminoalkyl)amino Acids and Nα-(ω-Carboxyalkyl)amino Acids
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An improved synthesis of a family of amino acids that contain ω-aminoalkyl groups and of a new family containing ω-carboxyalkyl groups linked to the α-amine is described. The synthesis was performed by alkylation of suitably monoprotected alkylenediamines and protected ω-amino acids with triflates of α-hydroxy acid esters. The reaction proceeded with inversion of configuration yielding optically pure products. The Nα-(ω-aminoalkyl)amino acids and Nα-(ω-carboxyalkyl)amino acids were orthogonally protected to allow their incorporation into peptides by solid-phase peptide synthesis (SPPS) methodology.
- Muller, Dan,Zeltser, Irena,Bitan, Gal,Gilon, Chaim
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p. 411 - 416
(2007/10/03)
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- Stereoselective Pseudomonas cepacia lipase mediated synthesis of α-hydroxyamides
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A new method for the synthesis of α-hydroxyamides via the Pseudomonas cepacia lipase catalyzed amidation of α-hydroxyesters in non-aqueous media is described. Reactivities of α-hydroxy benzyl esters are excellent, resulting in rapid conversions to good yields of α-hydroxyamides, while ethyl and methyl esters react more slowly, and some hindered esters show no reactivity under the conditions studied. Some benzyl esters react stereoselectively, producing excellent yields of asymmetric α-hydroxyamides.
- Adamczyk, Maciej,Grote, Jonathan,Rege, Sushil
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p. 2509 - 2512
(2007/10/03)
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- Synthesis of (15)N-Labelled Chiral Boc-Amino Acids from Triflates: Enantiomers of Leucine and Phenylalanine
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An efficient synthesis of (15)N-labelled chiral Boc-amino acids by triflate alkylation of di-tert-butyl iminodicarbonate is reported.Both enantiomers of Boc-Leucine and -phenylalanine were synthesized from commercial α-amino acids of opposite configuration via α-hydroxy carboxylic acids provided by diazotization, thus extending the scope of an earlier exploratory study.The high chiral purity of the final products was confirmed by HPLC.These labelled amino acid derivatives are suitable for direct application to the synthesis of labelled peptides.
- Degerbeck, Fredrik,Fransson, Bengt,Grehn, Leif,Ragnarsson, Ulf
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