排序方式: 共有21条查询结果,搜索用时 0 毫秒
11.
12.
13.
14.
15.
16.
17.
John E. Ladbury 《Chemistry & biology》1996,3(12):973-980
Recent data have highlighted the enigmatic role that water plays in biomolecular complexes. Water at the interface of a complex can increase the promiscuity of an interaction, yet it can also provide increased specificity and affinity. The ability to engineer water-binding sites into the interface between a drug and its target might prove useful in drug design. 相似文献
18.
Farrukh Vohidov Sarah E. Knudsen Paul G. Leonard Jun Ohata Michael J. Wheadon Brian V. Popp John E. Ladbury Zachary T. Ball 《Chemical science》2015,6(8):4778-4783
Src-family kinases (SFKs) play important roles in human biology and are key drug targets as well. However, achieving selective inhibition of individual Src-family kinases is challenging due to the high similarity within the protein family. We describe rhodium(ii) conjugates that deliver both potent and selective inhibition of Src-family SH3 domains. Rhodium(ii) conjugates offer dramatic affinity enhancements due to interactions with specific and unique Lewis-basic histidine residues near the SH3 binding interface, allowing predictable, structure-guided inhibition of SH3 targets that are recalcitrant to traditional inhibitors. In one example, a simple metallopeptide binds the Lyn SH3 domain with 6 nM affinity and exhibits functional activation of Lyn kinase under biologically relevant concentrations (EC50 ∼ 200 nM). 相似文献
19.
Chen Z Vohidov F Coughlin JM Stagg LJ Arold ST Ladbury JE Ball ZT 《Journal of the American Chemical Society》2012,134(24):10138-10145
In this study, we present advances in the use of rhodium(II) metallopeptides for protein modification. Site-specific, proximity-driven modification is enabled by the unique combination of peptide-based molecular recognition and a rhodium catalyst capable of modifying a wide range of amino-acid side chains. We explore catalysis based on coiled-coil recognition in detail, providing an understanding of the determinants of specificity and culminating in the demonstration of orthogonal modification of separate proteins in cell lysate. In addition, the concepts of proximity-driven catalysis are extended to include modification of the natural Fyn SH3 domain with metallopeptides based on a known proline-rich peptide ligand. The development of orthogonal catalyst-substrate pairs for modification in lysate, and the extension of these methods to new natural protein domains, highlight the capabilities for new reaction design possible in chemical approaches to site-specific protein modification. 相似文献
20.
Elucidating protein-protein interactions has been a central feature to understanding intracellular signal transduction. Many of the binding sites of the interacting proteins in these pathways are within highly sequentially homologous and structurally conserved domains. We challenge the dogma that mutual exclusivity in signalling is derived from a high level of specificity in these domains. 相似文献