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.