|
|
| Line 8: |
Line 8: |
| <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6r28 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6r28 OCA], [https://pdbe.org/6r28 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6r28 RCSB], [https://www.ebi.ac.uk/pdbsum/6r28 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6r28 ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6r28 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6r28 OCA], [https://pdbe.org/6r28 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6r28 RCSB], [https://www.ebi.ac.uk/pdbsum/6r28 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6r28 ProSAT]</span></td></tr> |
| </table> | | </table> |
| <div style="background-color:#fffaf0;">
| |
| == Publication Abstract from PubMed ==
| |
| Aberrant Ras signalling drives 30% of cancers and inhibition of Rho family small-GTPase signalling has been shown to combat Ras-driven cancers. Here we present the discovery of a 16mer cyclic peptide that binds to Cdc42 with nanomolar affinity. Affinity maturation of this sequence has produced a panel of derived candidates with increased affinity and modulated specificity for other closely related small-GTPases. The structure of the tightest binding peptide was solved by NMR and its binding site on Cdc42 determined. Addition of a cell penetrating sequence allowed the peptides to access the cell interior and engage with their target(s), modulating signalling pathways. In Ras-driven cancer cell models, the peptides have an inhibitory effect on proliferation and show suppression of both invasion and motility. As such they represent promising candidates for Rho-family small GTPase inhibitors and therapeutics targeting Ras-driven cancers. Our data adds to the growing literature demonstrating that peptides are establishing their place in the biologics arm of drug discovery.
| |
|
| |
| The discovery and maturation of peptide biologics targeting the small G protein Cdc42: a bioblockade for Ras-driven signalling.,Tetley GJN, Murphy NP, Bonetto S, Ivanova-Berndt G, Revell J, Mott HR, Cooley RN, Owen D J Biol Chem. 2020 Jan 20. pii: RA119.010077. doi: 10.1074/jbc.RA119.010077. PMID:31959628<ref>PMID:31959628</ref>
| |
|
| |
| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| |
| </div>
| |
| <div class="pdbe-citations 6r28" style="background-color:#fffaf0;"></div>
| |
| == References ==
| |
| <references/>
| |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
