Peptides derived from histidine and methionine-rich regions of copper transporter 1 exhibit anti-angiogenic property by chelating extracellular Cu.

Angiogenesis is a process of synthesis of new blood vessels from preexisting vasculature. Copper (Cu) as a micronutrient is important to many proteins for their physiological roles. Cu is transported by ceruloplasmin from liver to other parts of the body. Copper transporter 1 (CTR1) is a transmembrane protein which participate in Cu transport across the cell. It is also known to be involved in angiogenesis. In this study, we have designed three peptides from copper-binding regions of CTR1 which are rich in histidine and methionine. These peptides were screened for their inhibitory effect on angiogenesis in the HUVEC model. Mass spectroscopy studies revealed that all the three peptides derived from CTR 1 (Pep 1, 2, and 3) bound to Cu. The intracellular Cu levels estimated by atomic absorption spectroscopy showed decreased levels of copper in peptide-treated cells as compared to control. These peptides inhibited proliferation, migration, and tube formation in HUVEC by sequestering copper, preventing its entry into the cell and thereby inhibiting angiogenesis.