J Spiegel, PM Cromm, A Itzen, RS Goody, TN Grossmann, H Waldmann
Journal name: 
Angew Chem Int Ed Engl
Citation info: 
Small GTPases are molecular switches using GDP/GTP alternation to control numerous vital cellular processes. Although aberrant function and regulation of GTPases are implicated in various human diseases, direct targeting of this class of proteins has proven difficult, as GTPase signaling and regulation is mediated by extensive and shallow protein interfaces. Here we report the development of inhibitors of protein-protein interactions involving Rab proteins, a subfamily of GTPases, which are key regulators of vesicular transport. Hydrocarbon-stapled peptides were designed based on crystal structures of Rab proteins bound to their interaction partners. These modified peptides exhibit significantly increased affinities and include a stapled peptide (StRIP3) that selectively binds to activated Rab8a and inhibits a Rab8a-effector interaction in vitro.
E-pub date: 
24 Feb 2014
Users with this publication listed: 
Jochen Spiegel