R18 peptide

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aka difopein (dimeric fourteen- three-three peptide inhibitor)

Competitive inhibitor of binding to 14-3-3 proteins (all isoforms), with Kd = 80 nM (without isoform selectivity) found by phage display ( Wang et al 1999, PMID 10493820). R18 binds to same amphipathic grove as phosphorylated substrates of 14-3-3, although R18 itself is not phosphorylated . Petosa et al., 1998. PMID 9632691

Molecular Weight: 2.3 kDaltons

Peptide sequence:


Pro-His-Cys-Val-Pro-Arg-Asp-Leu-Ser-Trp-Leu-Asp-Leu-Glu-Ala- Asn-Met-Cys-Leu-Pro-OH

Discovery and characterization of R18:

B. Wang, H. Yang, Y.C. Liu, T. Jelinek, L. Zhang, E. Ruoslahti, et al., Isolation of high-affinity peptide antagonists of 14-3-3 proteins by phage display, Biochemistry. 38 (1999) 12499–12504. PMID 10493820

Binding to 14-3-3 grove:

C. Petosa, S.C. Masters, L.A. Bankston, J. Pohl, B. Wang, H. Fu, et al., 14-3-3zeta binds a phosphorylated Raf peptide and an unphosphorylated peptide via its conserved amphipathic groove, J Biol Chem. 273 (1998) 16305–16310. PMID 9632691