Anti-Microbial and Anti-Cancer Properties of Tat-IV13, A Hybrid Bi-Partite Peptide Containing The Short Non Active Iv13 Sequence of Human Ll37 Cathelecidin

Abstract

Therapeutic strategies based on optimization of the unique human LL37 cathelecin sequences including FK16, the core active sequence of LL37, have already been proposed. In this study we have characterized TatIV13 a new host defense hybrid peptide, that combined YGRRKKRRQRRR, the hydrophobic N-terminal fragment of HIV-1 Tat47-57 cell penetrating sequence, with IV13, a short IVQRIKDFLRNLV inactive sequence resulting from the deletion of the three N-terminal amino acid residues of FK16. Tat- IV13 displayed potent host defense inhibitory effects leading both to the survival inhibition of U87G cells, a glioblastoma model, and to the inhibition of the growth of S. agalactiae NEM316 ΔdltA strain, a Gram+ bacterial model. These results suggest that identification of hybrid specific Tat-cathelecidin peptides with high anti-tumor activity and anti-bactericidal activity may represent a powerful approach to identify new candidates for future therapeutic developments.