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51.
The total synthesis of 6-O-sulfo-sialylparagloboside is described. A suitably protected beta-D-GlcpNAc-(1-->3)-beta-D-Galp-(1-->4)-D-GlcpOSE derivative was glycosylated with an alpha-D-Neup5Ac-(2-->3)-D-Galp derived imidate to give the corresponding protected alpha-D-Neup5Ac-(2-->3)-beta-D-Galp-(1-->4)-beta-d-GlcpNAc-(1-->3)-beta-D-Galp-(1-->4)-D-GlcpOSE pentasaccharide derivative. Proper manipulation of the protecting groups of the pentasaccharide afforded the corresponding glycosyl imidate, which was coupled with (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol. Selective reduction of the azido group, N-acylation with octadecanoic acid, 6-O-sulfation of the GlcpNAc residue, and complete removal of the protecting groups gave the desired 6-O-sulfo-sialylparagloboside. 相似文献
52.
S. Rajesh Eiichi Ami Tomoya Kotake Tooru Kimura Yoshio Hayashi Yoshiaki Kiso 《Bioorganic & medicinal chemistry letters》2002,12(24):4567-3617
Z- and Fmoc-L-tetrahydrofuranylglycines have been obtained from L-vinylglycine through dipolar cycloaddition reaction, and its Fmoc derivative has been applied in the synthesis of modified S9 and S10 substrates of HIV-1 protease. These compounds mostly acted as strong inhibitors, rather than substrates, of the protease, probably due to the favourable interactions of the tetrahydrofuranylglycine moiety at the S(2) site. 相似文献
53.
Mio Kawabata Honoka Matsuo Takumi Koito Misaki Murata Tomoko Kubori Hiroki Nagai Mitsuo Tagaya Kohei Arasaki 《PLoS pathogens》2021,17(3)
Legionella pneumophila (L. pneumophila) is a gram-negative bacterium that replicates in a compartment that resembles the host endoplasmic reticulum (ER). To create its replicative niche, L. pneumophila manipulates host membrane traffic and fusion machineries. Bacterial proteins called Legionella effectors are translocated into the host cytosol and play a crucial role in these processes. In an early stage of infection, Legionella subverts ER-derived vesicles (ERDVs) by manipulating GTPase Rab1 to facilitate remodeling of the Legionella-containing vacuole (LCV). Subsequently, the LCV associates with the ER in a mechanism that remains elusive. In this study, we show that L. pneumophila recruits GTPases Rab33B and Rab6A, which regulate vesicle trafficking from the Golgi to the ER, to the LCV to promote the association of LCV with the ER. We found that recruitment of Rab6A to the LCV depends on Rab33B. Legionella effector SidE family proteins, which phosphoribosyl-ubiquitinate Rab33B, were found to be necessary for the recruitment of Rab33B to the LCV. Immunoprecipitation experiments revealed that L. pneumophila facilitates the interaction of Rab6 with ER-resident SNAREs comprising syntaxin 18, p31, and BNIP1, but not tethering factors including NAG, RINT-1, and ZW10, which are normally required for syntaxin 18-mediated fusion of Golgi-derived vesicles with the ER. Our results identified a Rab33B-Rab6A cascade on the LCV and the interaction of Rab6 with ER-resident SNARE proteins for the association of LCV with the ER and disclosed the unidentified physiological role of SidE family proteins. 相似文献
54.
C Galustian A Lubineau C le Narvor M Kiso G Brown T Feizi 《The Journal of biological chemistry》1999,274(26):18213-18217
The cell adhesion molecule L-selectin binds to 3'-sialyl-Lewis (Le)x and -Lea and to 3'-sulfo-Lex and -Lea sequences. The binding to 3'-sialyl-Lex is strongly affected by the presence of 6-O-sulfate as found on oligosaccharides of the counter receptor, GlyCAM-1; 6-O-sulfate on the N-acetylglucosamine (6-sulfation) enhances, whereas 6-O-sulfate on the galactose (6'-sulfation) virtually abolishes binding. To extend knowledge on the specificity of L-selectin, we have investigated interactions with novel sulfo-oligosaccharides based on the Lex pentasaccharide sequence. We observe that, also with 3'-sulfo-Lex, the 6-sulfation enhances and 6'-sulfation suppresses L-selectin binding. The 6'-sulfation without 3'-sialyl or 3'-sulfate gives no binding signal with L-selectin. Where the 6-sulfo,3'-sialyl-Lex is on an extended di-N-acetyllactosamine backbone, additional 6-O-sulfates on the inner galactose and inner N-acetylglucosamine do not influence the binding. Although binding to the 6,3'-sulfo-Lex and 6-sulfo, 3'-sialyl-Lex sequences is comparable, the former is a more effective inhibitor of L-selectin binding. This difference is most apparent when L-selectin is in paucivalent form (predominantly di- and tetramer) rather than multivalent. Indeed, as inhibitors of the paucivalent L-selectin, the 3'-sulfo-Lex series are more potent than the corresponding 3'-sialyl-Lex series. Thus, for synthetic strategies to design therapeutic oligosaccharide analogs as antagonists of L-selectin binding, those based on the simpler 3'-sulfo-Lex (and also the 3'-sulfo-Lea) would seem most appropriate. 相似文献
55.
Youhei Sohma Yoshio Hayashi Maiko Kimura Yousuke Chiyomori Atsuhiko Taniguchi Masato Sasaki Tooru Kimura Yoshiaki Kiso 《Journal of peptide science》2005,11(8):441-451
An efficient 'O-acyl isopeptide method' for the synthesis of difficult sequence-containing peptides was applied successfully to the synthesis of amyloid beta peptide (Abeta) 1-42 via a water-soluble O-acyl isopeptide of Abeta1-42, i.e. '26-O-acyl isoAbeta1-42' (6). This paper describes the detailed synthesis of Abeta1-42 focusing on the importance of resin selection and the analysis of side reactions in the O-acyl isopeptide method. Protected '26-O-acyl isoAbeta1-42' peptide resin was synthesized using 2-chlorotrityl chloride resin with minimum side reactions in comparison with other resins and deprotected crude 26-O-acyl isoAbeta1-42 was easily purified by HPLC due to its relatively good purity and narrow elution with reasonable water solubility. This suggests that only one insertion of the isopeptide structure into the sequence of the 42-residue peptide can suppress the unfavourable nature of its difficult sequence. The migration of O-acyl isopeptide to intact Abeta1-42 under physiological conditions (pH 7.4) via O--N intramolecular acyl migration reaction was very rapid and no other by-product formation was observed while 6 was stable under storage conditions. These results concluded that our strategy not only overcomes the solubility problem in the synthesis of Abeta1-42 and can provide intact Abeta1-42 efficiently, but is also applicable in the synthesis of large difficult sequence-containing peptides at least up to 50 amino acids. This synthesis method would provide a biological evaluation system in Alzheimer's disease research, in which 26-O-acyl isoAbeta1-42 can be stored in a solubilized form before use and then rapidly produces intact Abeta1-42 in situ during biological experiments. 相似文献
56.
A novel strategy for a more efficient synthesis of difficult sequence‐containing peptides, the S‐acyl isopeptide method, was developed and successfully applied. A model pentapeptide Ac–Val–Val–Cys–Val–Val–NH2 was synthesized via its water‐soluble S‐acyl isopeptide using an S‐acyl isodipeptide unit, Boc–Cys(Fmoc–Val)–OH. An S‐acyl isopeptide possessing excellent water solubility could be readily and quantitatively converted to the native peptide via an S N intramolecular acyl migration reaction at pH 7.4. Thus, the S‐acyl isopeptide method provides a useful tool in peptide chemistry. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
57.
58.
Hidaka K Kimura T Ruben AJ Uemura T Kamiya M Kiso A Okamoto T Tsuchiya Y Hayashi Y Freire E Kiso Y 《Bioorganic & medicinal chemistry》2008,16(23):10049-10060
Plasmepsin (Plm) is a potential target for new antimalarial drugs, but most reported Plm inhibitors have relatively low antimalarial activities. We synthesized a series of dipeptide-type HIV protease inhibitors, which contain an allophenylnorstatine-dimethylthioproline scaffold to exhibit potent inhibitory activities against Plm II. Their activities against Plasmodium falciparum in the infected erythrocyte assay were largely different from those against the target enzyme. To improve the antimalarial activity of peptidomimetic Plm inhibitors, we attached substituents on a structure of the highly potent Plm inhibitor KNI-10006. Among the derivatives, we identified alkylamino compounds such as 44 (KNI-10283) and 47 (KNI-10538) with more than 15-fold enhanced antimalarial activity, to the sub-micromolar level, maintaining their potent Plm II inhibitory activity and low cytotoxicity. These results suggest that auxiliary substituents on a specific basic group contribute to deliver the inhibitors to the target Plm. 相似文献
59.
Hajjaj H.M. Abdu-Allah Kozo Watanabe Koji Hayashizaki Chiaki Takaku Taichi Tamanaka Hiromu Takematsu Yasunori Kozutsumi Takeshi Tsubata Hideharu Ishida Makoto Kiso 《Bioorganic & medicinal chemistry letters》2009,19(19):5573-5575
Our previous study revealed that compound 1 (9-(4′-hydroxy-4-biphenyl)acetamido-9-deoxy-Neu5Gcα2-6GalOMP) has the most promising affinity for mCD22. Replacing the subterminal galactose residue of 1 with benzyl or biphenylmethyl as aglycone led to 38- and 20-fold higher potency, respectively. This discovery represents a new direction in inhibitor design suitable for pharmaceutical development. 相似文献
60.
Thomas Regnier Diganta Sarma Koushi Hidaka Usman Bacha Ernesto Freire Yoshio Hayashi Yoshiaki Kiso 《Bioorganic & medicinal chemistry letters》2009,19(10):2722-2727
A series of trifluoromethyl, benzothiazolyl or thiazolyl ketone-containing peptidic compounds as SARS-CoV 3CL protease inhibitors were developed and their potency was evaluated by in vitro protease inhibitory assays. Three candidates had encouraging results for the development of new anti-SARS compounds. 相似文献