Introduction:

CIGB-552 is a synthetic peptide that proved to be effective in reducing tumor size in animal models. The antitumor activity of the peptide is due to its cell penetration capacity and binding to the COMMD1 protein. This protein modulates the signaling pathways of the transcription factors NF-kB and HIF-1, that are important for tumor survival. The chemical optimization of a therapeutic peptide is based on structure-function relationship studies.

Objective:

To deepen the relationship of the structure of CIGB-552 with the antitumor properties

Methods:

It was evaluated the binding to the protein COMMD1 by test ELISA and surface plasmon resonance. They were performed internalization assays by confocal microscopy and cytometry. The inhibitory capacity of NF-kB and HIF-1 dependent on COMMD1 was evaluated in cell lines with genomic inactivation for COMMD1 and their parents.

Results:

CIGB-552 metabolites do not bind to COMMD1, have a lower penetration capacity and do not activate apoptosis. Both the endocytosis and transduction mechanisms are involved in the internalization of CIGB-552 in the 3 cell lines evaluated. It is confirmed that the anti-inflammatory and anti-angiogenic properties of the CIGB-552 peptide are mediated through COMMD1 and are not present in the CIGB-550 peptide.

Conclusions:

The CIGB-552 peptide contains the minimum and necessary amino acid sequence that grants it the properties of cell penetration, binding to its specific target, proapoptotic, anti-inflammatory and anti-angiogenic that make it a peptide with novel anticancer properties.

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