Showing papers by "Wei Wang published in 2010"
TL;DR: The structures indicate how the substituents of a small molecule that bind to the three subpockets of theMDM2/X-p53 interaction should be optimized for effective binding to MDM2 and/or MDMX.
Abstract: Intensive anticancer drug discovery efforts have been made to develop small molecule inhibitors of the p53-MDM2 and p53-MDMX interactions. We present here the structures of the most potent inhibitors bound to MDM2 and MDMX that are based on the new imidazo-indole scaffold. In addition, the structure of the recently reported spiro-oxindole inhibitor bound to MDM2 is described. The structures indicate how the substituents of a small molecule that bind to the three subpockets of the MDM2/X-p53 interaction should be optimized for effective binding to MDM2 and/or MDMX. While the spiro-oxindole inhibitor triggers significant ligand-induced changes in MDM2, the imidazo-indoles share similar binding modes for MDMX and MDM2, but cause only minimal induced-fit changes in the structures of both proteins. Our study includes the first structure of the complex between MDMX and a small molecule and should aid in developing efficient scaffolds for binding to MDMX and/or MDM2.
214 citations
TL;DR: An efficient and flexible 2-step procedure to complex multicyclic indole alkaloid-type compounds involving Ugi MCR and Pictet-Spengler reaction is communicated.
64 citations
TL;DR: The newly discovered natural product bacillamide C and several derivatives were convergently synthesized for the first time and in only three steps and shows the synthetic pathway to related natural products.
Abstract: The newly discovered natural product bacillamide C and several derivatives were convergently synthesized for the first time and in only three steps. The key transformation constitutes a thiazole Ugi multicomponent reaction. These compounds will serve to elucidate chemical biology and SAR of this potent anti-algae natural product and shows the synthetic pathway to related natural products.
29 citations
TL;DR: In this article, a universal cloaking scheme is proposed to hide the position of an object by shifting its scattering without a scaling effect for distance, independent of the direction of incident wave and observation.
Abstract: By introducing the concept of 'minifying layer', we propose a universal device to hide the position of an object by shifting its scattering without a scaling effect for distance, independent of the direction of incident wave and observation. Unlike the previously reported similar cloaks whose configurations are relevant to the objects to be cloaked, the design here is able to shift the scattering of various objects by one cloak. Moreover, by adjusting the parameter of the 'minifying layer', a tunable magnifying or even minifying effect on the shifted scattering can also be achieved. The performances of the devices are demonstrated by finite element simulations. This design provides a more flexible way to shift the scattering of an object, and thus can be expected to have wide applications.
9 citations