406213-76-1Relevant articles and documents
Antibody drug conjugate, intermediate, preparation method, pharmaceutical composition and uses thereof
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Page/Page column 207; 208; 210, (2019/11/11)
Disclosed are an antibody drug conjugate IB, which uses ether linkages for connection, and improves the water solubility, stability and cytotoxicity in vivo and in intro, and an intermediate, a pharmaceutical composition, and uses of the antibody drug conjugate. The antibody drug conjugate has simple synthetic steps and a high yield.
Target Identification of Yaku'amide B and Its Two Distinct Activities against Mitochondrial FoF1-ATP Synthase
Kitamura, Kai,Itoh, Hiroaki,Sakurai, Kaori,Dan, Shingo,Inoue, Masayuki
supporting information, p. 12189 - 12199 (2018/09/25)
Yaku'amide B (1b) is a structurally unique tetradecapeptide bearing four β,β-dialkylated α,β-unsaturated amino acid residues. Growth-inhibitory profile of 1b against a panel of 39 human cancer cell lines is distinct from those of clinically used anticancer drugs, suggesting a novel mechanism of action. We achieved total syntheses of chemical probes based on 1b and elucidated the cellular target and mode of action of 1b. Fluorescent (3, 4) and biotinylated (5, 6) derivatives of 1b were prepared for cell imaging studies and pull-down assays, respectively. In addition, the unnatural enantiomer of 1b (ent-1b) and its fluorescent probe (ent-3) were synthesized for control experiments. Subcellular localization analysis using 3 and 4 showed that 1b selectively accumulates in the mitochondria of MCF-7 human breast cancer cells. Pull-down assays with 6 revealed FoF1-ATP synthase as the major target protein of 1b. Consistent with these findings, biochemical activity assays showed that 1b inhibits ATP production catalyzed by mitochondrial FoF1-ATP synthase. Remarkably, 1b was also found capable of enhancing the ATP hydrolytic activity of FoF1-ATP synthase. On the other hand, ent-1b inhibits ATP synthesis more weakly than does 1b and does not affect ATP hydrolysis, suggesting the stereospecific requirement for the characteristic multimodal functions of 1b. These findings corroborate that 1b causes growth arrest in MCF-7 cells by inhibiting ATP production and enhancing ATP hydrolysis, thereby depleting the cellular ATP pool. This study provides, for the first time, a structural basis for the design and development of anticancer agents exploiting the novel mode of action of 1b.
Synthesis and molecular recognition studies of the HNK-1 trisaccharide and related oligosaccharides. the specificity of monoclonal anti-HNK-1 antibodies as assessed by surface plasmon resonance and STD NMR
Tsvetkov, Yury E.,Burg-Roderfeld, Monika,Loers, Gabriele,Arda, Ana,Sukhova, Elena V.,Khatuntseva, Elena A.,Grachev, Alexey A.,Chizhov, Alexander O.,Siebert, Hans-Christian,Schachner, Melitta,Jimenez-Barbero, Jesus,Nifantiev, Nikolay E.
supporting information; experimental part, p. 426 - 435 (2012/03/11)
The human natural killer cell carbohydrate, HNK-1, plays function-conducive roles in peripheral nerve regeneration and synaptic plasticity. It is also the target of autoantibodies in polyneuropathies. It is thus important to synthesize structurally relate
