title: Designed antimicrobial and antitumor peptides with high selectivity.
abstract: We report a new class of cationic amphiphilic peptides with short sequences, G(IIKK)(n)I-NH(2) (n = 1-4), that can kill Gram-positive and Gram-negative bacteria as effectively as several well-known antimicrobial peptides and antibiotics. In addition, some of these peptides possess potent antitumor activities against cancer cell lines. Moreover, their hemolytic activities against human red blood cells (hRBCs) remain remarkably low even at some 10-fold bactericidal minimum inhibitory concentrations (MICs). When bacteria or tumor cells are cocultured with NIH 3T3 fibroblast cells, G(IIKK)(3)I-NH(2) showed fast and strong selectivity against microbial or tumor cells, without any adverse effect on NIH 3T3 cells. The high selectivity and associated features are attributed to two design tactics: the use of Ile residues rather than Leu and the perturbation of the hydrophobic face of the helical structure with the insertion of a positively charged Lys residue. This class of simple peptides hence offers new opportunities in the development of cost-effective and highly selective antimicrobial and antitumor peptide-based treatments.
authors.affiliation: State Key Laboratory of Heavy Oil Processing and the Centre for Bioengineering and Biotechnology, China University of Petroleum (East China), Qingdao 266555, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.forename: Cuixia
authors.initials: C
authors.lastname: Chen
authors.forename: Shengzhong
authors.initials: S
authors.lastname: Zhang
authors.forename: Xichen
authors.initials: X
authors.lastname: Zhao
authors.forename: Hai
authors.initials: H
authors.lastname: Xu
authors.forename: Xiubo
authors.initials: X
authors.lastname: Zhao
authors.forename: Jian R
authors.initials: JR
authors.lastname: Lu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects; D002942:Circular Dichroism; D004912:Erythrocytes / Q000187:drug effects; D018922:HL-60 Cells; D006367:HeLa Cells; D053878:Hemolytic Agents / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D020128:Inhibitory Concentration 50; D051379:Mice; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D017433:Protein Structure, Secondary
chemical_list: D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents; D053878:Hemolytic Agents