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Selective cytotoxicity following Arg‐to‐Lys substitution in tritrpticin adopting a unique amphipathic turn structure
Author(s) -
Yang Sung-Tae,
Shin Song Yub,
Lee Chul Won,
Kim Yong-Chul,
Hahm Kyung-Soo,
Kim Jae Il
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)00266-7
Subject(s) - chemistry , liposome , amphiphile , peptide , cationic polymerization , amine gas treating , stereochemistry , antimicrobial peptides , amino acid , turn (biochemistry) , biochemistry , organic chemistry , copolymer , polymer
In antimicrobial peptides, the cationic property due to basic amino acids has been widely recognized as an important factor to promote electrostatic interaction with negatively charged phospholipids. However, little is known about the differences between two basic residues, Arg and Lys, in membrane binding affinity. Tritrpticin is an Arg‐ or Trp‐rich antimicrobial peptide with a broad spectrum of antibacterial and antifungal activity. To investigate the structural and functional differences between Arg and Lys residues, here we designed and synthesized Arg‐containing peptides, tritrpticin and SYM11, and their counterpart Lys‐substituted peptides, TRK and SYM11KK, respectively. Although there were no remarkable conformational differences between Arg‐containing and Lys‐substituted peptides, TRK and SYM11KK exhibited almost two‐fold enhanced antibacterial activity but significantly reduced hemolytic activity as compared to tritrpticin and SYM11, respectively. Furthermore, Arg‐containing peptides showed strong binding affinity to both zwitterionic and anionic liposomes, whereas Lys‐substituted peptides interacted weakly with zwitterionic liposomes but strongly with anionic liposomes. These results suggest that the primary amine of Lys interacts less electrostatically with zwitterionic phospholipids than the guanidinium group of Arg. Our results obtained in this study may be helpful in the design of drugs that target negatively charged phospholipids.