A cyclic peptide, L1AD3, induces early signs of apoptosis in human leukemic T‐cell lines

Abstract

L1AD3 is a small cyclic synthetic peptide designed to resemble the first loop of a cobra venom cytotoxin. Instead of inducing membrane disruption similar to that caused by the parent toxin, L1AD3 promotes extensive and unusually rapid apoptosis in leukemic T-cells without making the plasma membrane permeable to small fluorescent dyes. Within 4 h, micromolar concentrations of L1AD3 almost totally inhibit thymidine incorporation, and ATP levels decrease significantly. By contrast, normal human white blood cells are not affected by L1AD3, nor is heart cell function affected by it. If L1AD3 kills by interacting with targets that are different from those of currently applied agents, this peptide, or a derivative of it, could become a useful adjunct for cancer chemotherapy.

Cobra Cytotoxins: Structural Organization and Antibacterial Activity

“…We believe that the next step will be designing peptides based on CTs amino acid sequences. Some steps have already been taken in this direction, and one of the peptides, L1AD3 [ 81 , 82 ], can be used to treat leukemia. It is likely that there will be more examples in the future.…”

“…It was reported earlier that 7- to 12-residue long peptides from loop I of the CT4 of N. mossambica display in vivo toxicity, albeit lesser than that of the original toxin [ 80 ]. The 14-membered cyclic peptide (with one disulfide bond) L1AD3 has the amino acid sequence of loop I of the CT3 of N. atra and can induce apoptosis in leukemic T-cells [ 81 , 82 ] when used at micromolar concentrations. The peptide has a β-hairpin conformation in aqueous solutions, similar to the corresponding moiety within the original CT.…”