Anticancer nanometre-biomissiles carrying a leucine insulator and an antibody complementarity-determining region

Abstract

The tumour specificities and potency of miniaturized cancer targeting peptides are among the major issues of current cancer research. Over 100 peptides were evaluated in this study. According to the observations, leucine could sustain the antibacterial and anticancer efficacy of (leucine/lysine) n ((L/K)n) peptides across different assay conditions, whereas (valine/lysine) n ((V/K)n) and (isoleucine/lysine) n ((I/K)n) peptides were less effective. Tumour targeting peptides, consisting of a leucine/lysine peptide and an antibody complementarity-determining region (CDR) fragment against CD47 receptor separated by a leucine4 insulator, eradicated 100% of the lung cancer A549 cells at 100 p.m concentration after 24 h of incubation. It also inhibited tumour growth in a mouse model of colon cancer cells, showing extensive apoptosis at the end of the treatment. Our data suggest that leucine insulators could be effective spacers in the design of targeted or plurispecific peptide drugs given the lack of ϭ-ϭhyperconjugation on ß-carbon and the lack of strong van der Waals interactions between the side group and the carbonyl group. Significant reduction of hemolysis by P45-3 with terminal alanine replacement on peptide P129 suggests that biosafety attribute of a peptide can be substantially improved.