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.