Functional Analysis of Novicidin Peptide: Coordinated Delivery System for Zinc via Schiff Base Ligand,Bioconjugate Chemistry

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Functional Analysis of Novicidin Peptide: Coordinated Delivery System for Zinc via Schiff Base Ligand
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2018-08-07 00:00:00 , DOI: 10.1021/acs.bioconjchem.8b00370
Vedran Milosavljevic _{1,

2} , Yazan Haddad _{1,

2} , Amitava Moulick _{1,

2} , Hana Buchtelova _{1,

2} , Roman Guran _{1,

2} , Tomas Pospisil ₃ , Kamila Stokowa-Sołtys ₄ , Zbynek Heger _{1,

2} , Lukas Richtera _{1,

2} , Pavel Kopel _{1,

2} , Vojtech Adam _{1,

2}

Affiliation

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.

中文翻译：

Novicidin肽的功能分析：经由Schiff配体的锌协同递送系统

Novicidin（NVC）是一种穿透膜的肽，可与Zn-Schiff碱形成稳定的复合物，并具有令人感兴趣的抗肿瘤选择性。我们研究了NVC衍生物，以确定关键氨基酸在毒性，螺旋度和Zn-席夫碱复合物的结合中的功能性作用。修饰的衍生物突出了肽长度和螺旋度在毒性和膜渗透中的作用。从位置1和2除去Lys会大大增加破坏膜的能力。N-的修剪末端残基显着增加了肽螺旋度的稳定性，增强了穿透性能。甘氨酸残基衍生物破坏了肽弯曲在膜渗透和毒性中的作用。用Ile或Lys取代中心Gly衍生物后，这些肽保留了毒性。这些结果说明中心螺旋弯曲在NVC毒性中的次要作用。结合位点肽衍生物将His残基鉴定为唯一的Zn-Schiff碱基结合位点，并消除了其他芳香族残基的作用。

更新日期：2018-08-07

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