Figure 1.

Illustration of cleavage process and the binding events of cyclic iRGD [CRGDKGPDC] peptide. (A) iRGD is proteolytically cleaved to expose the cryptic C-end Rule (CendR) motif. The cleavage sites are indicated with red lines. (B) iRGD binds with integrins. As an example, we present the structure of integrin αvβ3 complexed with cyclo (RGDf-NV) reproduced from PDB code 1I5G [68]. (C) After cleavage, the arginine or lysine of the CendR motif binds to the b1 domain of neuropilin-1 (NRP-1). The presented structure was reproduced from PDB code 2ORZ showing the binding event of NRP-1 and Tuftsin mediated by arginine moiety [55,69,70]. The spheres represent the binding residues of polypeptides and blue ball-sticks represent non-binding residues. The color indicates the corresponding sequence of peptides.