Study of the mechanism of action of anoplin, a helical antimicrobial decapeptide with ion channel-like activity, and the role of the amidated C-terminus.
Anoplin, an antimicrobial, helical decapeptide from wasp venom, looses its biological activities by mere deamidation of its C-terminus. Secondary structure determination, by circular dichroism spectroscopy in amphipathic environments, and lytic activity in zwitterionic and anionic vesicles showed quite similar results for the amidated and the carboxylated forms of the peptide. The deamidation of the C-terminus introduced a negative charge at an all-positive charged peptide, causing a loss of amphipathicity, as indicated by molecular dynamics simulations in TFE/water mixtures and this subtle modification in a peptide's primary structure disturbed the interaction with bilayers and biological membranes. Although being poorly lytic, the amidated form, but not the carboxylated, presented ion channel-like activity on anionic bilayers with a well-defined conductance step; at approximately the same concentration it showed antimicrobial activity. The pores remain open at trans-negative potentials, preferentially conducting cations, and this situation is equivalent to the interaction of the peptide with bacterial membranes that also maintain a high negative potential inside.
Dos Santos Cabrera
Marcia Perez
MP
USP, University of São Paulo, Department of Physiology and Biophysics, Biomedical Sciences Institute, São Paulo, SP, Brazil. cabrera.marcia@gmail.com
Arcisio-Miranda
Manoel
M
Broggio Costa
Sabrina Thais
ST
Konno
Katsuhiro
K
Ruggiero
José Roberto
JR
Procopio
Joaquim
J
Ruggiero Neto
João
J
D000577:Amides / Q000737:chemistry*; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D002942:Circular Dichroism; D008051:Lipid Bilayers; D014862:Wasp Venoms / Q000737:chemistry / Q000494:pharmacology*
D000577:Amides; D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers; D014862:Wasp Venoms; C443041:anoplin