Single Amino Acid Change in Metallothionein Metal-Binding Cluster Influences Interaction with Cisplatin

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216305%3A26620%2F13%3APU105675" target="_blank" >RIV/00216305:26620/13:PU105675 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/62156489:43210/13:00213567 RIV/00216208:11310/13:10135334 RIV/00216208:11130/13:10135334 RIV/00064203:_____/13:10135334

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Single Amino Acid Change in Metallothionein Metal-Binding Cluster Influences Interaction with Cisplatin

Popis výsledku v původním jazyce

The issue of tumour cell resistance to anticancer drugs is a major problem in the treatment of this grave disease and it is still not satisfactorily explained. Its base lies in the interaction of a cytostatic with biomolecules synthesized by tumour cells. One of the generally accepted mechanisms of resistance to some metal based cytostatics is the overexpression of metallothionein in tumour cells. In this study, electrochemical profile of interaction between 23 sulphur-rich fragments of the metal-binding protein metallothionein and cisplatin was studied. To evaluate the results, interaction constants were suggested. Here, we found that the maximum increased interaction (more than 100 %) occurred, when conservative aminoacids were substituted for more than one position outside the cysteine cluster. On the contrary, amino acid substitution within the cysteine cluster led to a reduction in interaction constants (up to 10-25% of average). This result clearly indicates that aminoacids outside cysteine binding motif are of high importance for interactions of metallothionein with cisplatin.Based on the results it can be assumed that the substitution of individual aminoacids in the peptide chain of protein markedly influences the interaction with cisplatin, which could be used for designing new types of cytostatics.

Název v anglickém jazyce

Single Amino Acid Change in Metallothionein Metal-Binding Cluster Influences Interaction with Cisplatin

Popis výsledku anglicky

The issue of tumour cell resistance to anticancer drugs is a major problem in the treatment of this grave disease and it is still not satisfactorily explained. Its base lies in the interaction of a cytostatic with biomolecules synthesized by tumour cells. One of the generally accepted mechanisms of resistance to some metal based cytostatics is the overexpression of metallothionein in tumour cells. In this study, electrochemical profile of interaction between 23 sulphur-rich fragments of the metal-binding protein metallothionein and cisplatin was studied. To evaluate the results, interaction constants were suggested. Here, we found that the maximum increased interaction (more than 100 %) occurred, when conservative aminoacids were substituted for more than one position outside the cysteine cluster. On the contrary, amino acid substitution within the cysteine cluster led to a reduction in interaction constants (up to 10-25% of average). This result clearly indicates that aminoacids outside cysteine binding motif are of high importance for interactions of metallothionein with cisplatin.Based on the results it can be assumed that the substitution of individual aminoacids in the peptide chain of protein markedly influences the interaction with cisplatin, which could be used for designing new types of cytostatics.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CG - Elektrochemie

OECD FORD obor

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Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2013

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

INTERNATIONAL JOURNAL OF ELECTROCHEMICAL SCIENCE

ISSN

1452-3981

e-ISSN

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Svazek periodika

8

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

RS - Srbská republika

Počet stran výsledku

10

Strana od-do

2625-2634

Kód UT WoS článku

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EID výsledku v databázi Scopus

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