113757-76-9Relevant academic research and scientific papers
Synthesis of an STnThr analogue, structurally based on a TnThr antigen mimetic
Papi, Francesco,Paris, Arnaud,Lafite, Pierre,Daniellou, Richard,Nativi, Cristina
supporting information, p. 7366 - 7372 (2020/10/13)
The monosaccharide Tn and the disaccharide STn are tumor antigens with similar structures and common biosynthetic pathways. Both are always over-expressed simultaneously on tumor cell surfaces. We report herein the efficient synthesis of the STnThr antigen analogue 2, featuring the immunogenic TnThr mimetic 1 aglycon. Analogously to the native STn, 2 is recognized by the influenza N1 neuraminidase. A model of the N1·2 complex showed the sialyl moiety of 2 well nested in the active site pocket, with docking unaffected by the rigid aglycon. The analogue 2 is, therefore, in association with mimetic 1, a good determinant for the design of new multiantigen cancer vaccines.
Structure-based design and synthesis of C-1- and C-4-modified analogs of zanamivir as neuraminidase inhibitors
Feng, Enguang,Shin, Woo-Jin,Zhu, Xuelian,Li, Jian,Ye, Deju,Wang, Jiang,Zheng, Mingyue,Zuo, Jian-Ping,No, Kyoung Tai,Liu, Xian,Zhu, Weiliang,Tang, Wei,Seong, Baik-Lin,Jiang, Hualiang,Liu, Hong
, p. 671 - 684 (2013/04/10)
In order to exploit the 430-cavity in the active sites of neuraminidases, 22 zanamivir analogs with C-1 and C-4 modification were synthesized, and their inhibitory activities against both group-1 (H5N1, H1N1) and group-2 neuraminidases (H3N2) were determined. Compound 9f exerts the most potency, with IC50 value of 0.013, 0.001, and 0.09 μM against H3N2, H5N1, and H1N1, which is similar to that of zanamivir (H3N2 IC50 = 0.0014 μM, H5N1 IC50 = 0.012 μM, H1N1 IC50 = 0.001 μM). Pharmacokinetic studies of compound 9f in rats showed a much longer plasma half-life (t1/2) than that of zanamivir following administration (po dose). Molecular modeling provided information about the binding model between the new inhibitors and neuraminidase, with the elongated groups at the C-1-position being projected toward the 430-loop region. This study may represent a novel starting point for the future development of improved antiflu agents.
Solution phase synthesis of (1→5)-amide linked sugar amino acid dimers derived from sialic acids
Gervay, Jacquelyn,Flaherty, Terrence M.,Nguyen, Can
, p. 1493 - 1496 (2007/10/03)
Carboxy-protected amino derivatives and amino-protected carboxy derivatives of three different C-2 analogs as well as a 2,3-dehydro NeuAc were prepared. These monomers were coupled in solution using BOP activation of the carboxy terminus to form (1→5)-amide linked dimers of sialyl amino acid derivatives.
