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.
Highlights
Cationic anti-microbial peptides (CAMPs) are important components of the innate immune response with anti-infective and immunomodulatory activities [1, 2]
HCAP-18 is mainly stored in neutrophil-specific granules, and LL37 can be detectable in body fluids, including airway surface liquid, plasma, urine, breast milk and sweat [5]
We have recently reported that specific cellular or virally encoded sequences can display LL37-like host defense properties such as inhibition of U87G cells glioblastoma survival and inhibition of the growth of S. agalactiae NEM316 ΔdltA strain, a Gram+ bacterial model [12, 13]
Summary
Cationic anti-microbial peptides (CAMPs) are important components of the innate immune response with anti-infective and immunomodulatory activities [1, 2]. In this regard, LL-37 the active form of an unique human cathelecidin gene is a cationic, amphipathic peptide of 4.5 kDa with an a-helical structure that results from a proteinase 3 mediated proteolytic cleavage of a 18-kDa precursor HCT18 protein [3, 4]. We have recently reported that specific cellular or virally encoded sequences can display LL37-like host defense properties such as inhibition of U87G cells glioblastoma survival and inhibition of the growth of S. agalactiae NEM316 ΔdltA strain, a Gram+ bacterial model [12, 13]. We previously found that both FK16 alone or an hybrid bipartite peptide containing cell penetrating HIV-1 Tat and FK16 sequences display similar inhibitory effects against U87G cells glioblastoma and S. agalactiae NEM316 ΔdltA strain [13]
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