NC-100717: A versatile RGD peptide scaffold for angiogenesis imaging

Targeting the molecular pathways associated with angiogenesis offers great potential in detecting disease pathology using in vivo imaging technologies. Initiation of angiogenesis requires activation and migration of endothelial cells in order for neovascularization to proceed. Endothelial cells associate with the extracellular matrix through specific interactions with a variety of cell adhesion receptors known as integrins. Peptides containing the tripeptide sequence RGD are known to bind with high affinity to the αvβ3 and αvβ5 integrins associated with angiogenesis. We present herein the synthesis and in vitro binding affinity of the RGD-containing peptide NC-100717 and a range of molecular probes derived from this intermediate.

Graphical abstractThe development of a robust platform for the in vivo targeting of the integrins associated with angiogenesis is described. Derivatization of the core peptide NC-100717 with a range of reporter groups by amide bond formation at the ε-amino group of lysine gave a variety of molecular probes suitable for diagnostic imaging. All conjugates had affinities in the low nanomolar range.Figure optionsDownload full-size imageDownload as PowerPoint slide