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Facile fabrication of promising protein tyrosine phosphatase (PTP) inhibitor entities based on [`]clicked' serine/threonine-monosaccharide hybrids

X.-P. He, Q. Deng, L.-X. Gao, C. Li, W. Zhang, Y.-B. Zhou, Y. Tang, X.-X. Shi, J. Xie, J. Li, G.-R. Chen and K. Chen Bioorg. Med. Chem., 2011, 19 (13), 3892-3900

Références :

Bioorg. Med. Chem., 2011, 19 (13), 3892-3900

Auteur(s) : 

X.-P. He, Q. Deng, L.-X. Gao, C. Li, W. Zhang, Y.-B. Zhou, Y. Tang, X.-X. Shi, J. Xie, J. Li, G.-R. Chen and K. Chen


Protein tyrosine phosphatases (PTPs) are well-validated therapeutic targets for many human major diseases. The development of their potent inhibitors has therefore become a main focus of both academia and the pharmaceutical industry. We report herein a facile strategy toward the fabrication of new and competent PTP inhibitor entities by simply 'clicking' alkynyl amino acids onto diverse azido sugar templates. Triazolyl glucosyl, galactosyl, and mannosyl serine and threonine derivatives were efficiently synthesized via click reaction, which were then identified as potent CDC25B and PTP1B inhibitors selective over a panel of homologous PTPs tested. Their inhibitory activity and selectivity were found to largely lie on the structurally and configurationally diversified monosaccharide moieties whereon serinyl and threoninyl residues were introduced. In addition, MTT assay revealed the triazole-connected sugar-amino acid hybrids may also inhibit the growth of several human cancer cell lines including A549, Hela, and especially HCT-116. On the basis of such compelling evidence, we consider that this compound series could furnish promising chemical entities serving as new CDC25B and PTP1B inhibitors with potential cellular activity. Furthermore, the [`]click' strategy starting from easily accessible and biocompatible amino acids and sugar templates would allow the modular fabrication of a rich library of new PTP inhibitors efficaciously and productively.




Type :
Publication
Dates :
Paru le 27 mai 2011
Informations complémentaires :
doi: 10.1016/j.bmc.2011.05.049

 

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