Figure captions
Figure 1: Process of generation of antitumor peptide CIGB-552.The “second generation” peptide CIGB-552 was obtained by chemical modifications of L2, an antitumor peptide developed from an alanine library from CIGB-550, the LPS binding region of the LALF protein. The image illustrates the incorporation of D-aminoacids and N-terminal modifications in the peptide L2 to obtain CIGB-552. The properties acquired by each peptide are showed inside color boxes.
Figure 2: Pre-clinical summary of CIGB-552 as novel antitumor peptide. PPI: Predicted Protein-Protein Interactions.
Figure 3: Model of molecular mechanism of CIGB-552.(A) Tumor cell is characterized by inhibition of Apoptosis and NF-kB activation. COMMD1 is downregulated by proteasomal degradation. When CIGB-552 penetrates the cell (B) , it interacts with COMMD1 inducing its nuclear translocation. Once in the nucleus, COMMD1 inhibits the NF-kB transcriptional activity leading eventually to a process of Apoptosis. In the cytosol the complex COMMD1-CIGB-552 activates the apoptotic pathway through oxidative stress and the modulation of Bax/Bcl-2 ratio. Red arrows indicate inhibition and green arrows indicate activation. PS: phosphatidilserine, SOD1: superoxide dismutase 1, C: cytochrome C.
Figure 4: CIGB-552 and its main metabolites. The analysis of CIGB-552 stability in serum and its characterization by ESI-MS (electrospray ionization mass spectrometry) identified the main metabolites of CIGB-552. The evaluation of in vitro properties of these metabolites, demonstrated that aminoacids of C-terminal ending are essential for antitumor activity. The properties of each metabolite are summarized in color boxes. The color scale indicates the nature of the effect.