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MILOSAVLJEVIĆ, V. HADDAD, Y. MOULICK, A. BUCHTELOVÁ, H. GURÁŇ, R. POSPÍŠIL, T. STOKOWA-SOLTYS, K. HEGER, Z. RICHTERA, L. KOPEL, P. ADAM, V.
Original Title
Functional Analysis of Novicidin Peptide: Coordinated Delivery System for Zinc via Schiff Base Ligand
Type
journal article in Web of Science
Language
English
Original Abstract
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.
Keywords
Novicidin (NVC); Zn-Schiff base complex
Authors
MILOSAVLJEVIĆ, V.; HADDAD, Y.; MOULICK, A.; BUCHTELOVÁ, H.; GURÁŇ, R.; POSPÍŠIL, T.; STOKOWA-SOLTYS, K.; HEGER, Z.; RICHTERA, L.; KOPEL, P.; ADAM, V.
Released
30. 9. 2018
ISBN
1043-1802
Periodical
BIOCONJUGATE CHEMISTRY
Year of study
29
Number
9
State
United States of America
Pages from
2954
Pages to
2969
Pages count
16
BibTex
@article{BUT150614, author="Vedran {Milosavljević} and Yazan Abdulmajeed Eyadh {Haddad} and Amitava {Moulick} and Hana {Michálková} and Roman {Guráň} and Tomáš {Pospíšil} and Kamila {Stokowa-Soltys} and Zbyněk {Heger} and Lukáš {Richtera} and Pavel {Kopel} and Vojtěch {Adam}", title="Functional Analysis of Novicidin Peptide: Coordinated Delivery System for Zinc via Schiff Base Ligand", journal="BIOCONJUGATE CHEMISTRY", year="2018", volume="29", number="9", pages="2954--2969", doi="10.1021/acs.bioconjchem.8b00370", issn="1043-1802" }