Novicidin (NVC), is a membrane-penetrating peptide, which forms a stable complex with Zn-Schiff base with interesting antitumor selectivity. We studied NVC derivatives to determine functional roles of key amino acids in toxicity, helicity, and binding of the Zn-Schiff base complex. Trimmed derivatives highlighted the role of peptide length and helicity in toxicity and membrane penetration. The removal of Lys from position 1 and 2 strongly increases the ability to disrupt the membranes. The trimming of the N-terminal residues significantly increases the stability of peptide helicity enhancing penetrating properties. Gly residue derivatives undermined a role of peptide bending in membrane penetration and toxicity. After the substitution of the central Gly derivatives with Ile or Lys, the peptides retained toxicity. These results illustrate the minor role of central helix bending in NVC toxicity. Binding-site-peptide derivatives identified His residue as the sole Zn-Schiff base binding site and eliminated the role of other aromatic residues.

• MeSH
• glycin chemie   MeSH
• kationické antimikrobiální peptidy aplikace a dávkování   chemie   toxicita   MeSH
• konformace proteinů MeSH
• lidé MeSH
• ligandy MeSH
• nádorové buněčné linie MeSH
• permeabilita buněčné membrány MeSH
• protonová magnetická rezonanční spektroskopie MeSH
• Schiffovy báze chemie   MeSH
• sekvence aminokyselin MeSH
• spektrometrie hmotnostní - ionizace laserem za účasti matrice MeSH
• spektroskopie infračervená s Fourierovou transformací MeSH
• systémy cílené aplikace léků * MeSH
• vazebná místa MeSH
• zinek aplikace a dávkování   chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH