Origin of CIGB-552 peptide
In the Centre for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba, Vallespi and colleagues obtained an antimicrobial peptide against septic shock designed from the region 31-52 of the Limulusanti-LPS factor (LALF), a protein derived from the Horseshoe crabLimulus polyfemus (Vallespi, Colas, Garay, Reyes, & Arana, 2004). The peptide CIGB-550 (LALF31-52) demonstrated cell penetrating capacity due to net positive charge and amphipathic structure by alternating positive/ hydrophobic basic residues. It showed the capacity to bind, neutralize bacterial lipopolisacharide (LPS) and block the inflammatory response mediated by this molecule. Vallespi et al. demonstrated anti-inflammatory and immunomodulatory properties for CIGB-550, but also showed an antiviral effect for this peptide, mediated by IFN-γ and IFN-α (Vallespi et al., 2003). It has been reported that antimicrobial peptides exhibit a broad spectrum of cytotoxic activity against cancer cells (Hoskin & Ramamoorthy, 2008) and CIGB-550 is no an exception. The ability to inhibit processes associated with heparin, such as anticoagulation, angiogenesis, and tumor cell proliferation, was attributed to this peptide, although there are no experimental data supporting this. In order to study the structure-function relationship of LALF31-52 and its connection with the biological properties attributed to the peptide, a synthetic library was generated by alanine scanning (Vallespi et al., 2010). The resulting peptides were evaluated by LPS binding ability, antitumor effect, penetration capacity to live cells and immunostimulatory activity. These results lead to the development of L-2, a peptide optimized for anticancer activity. L-2 has lost its LPS binding capacity, however is a powerful cytotoxic agent against murine and human tumor cell lines (Vallespi et al., 2010). One of the weaknesses of the peptides as drugs is the short half-life and fast elimination (Fosgerau & Hoffmann, 2015). By modifications in the primary structure of L-2, we have developed a second-generation peptide as anticancer drug for evaluating in clinical trials named CIGB-552 (Figure 1). This peptide maintains the cell penetrating capacity and shows a higher antitumor effect in comparison to CIGB-550 and L-2.