Detail publikace

Vliv jednoaminokyselinové změny kovové vazby metalothioneinu v interakci s cysplatinou

ZÍTKA, O. KOMÍNKOVÁ, M. SKALIČKOVÁ, S. ŠKUTKOVÁ, H. PROVAZNÍK, I. ECKSCHLAGER, T. STIBOROVÁ, M. TRNKOVÁ, L. ADAM, V. KIZEK, R.

Originální název

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

Český název

Vliv jednoaminokyselinové změny kovové vazby metalothioneinu v interakci s cysplatinou

Anglický název

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

Typ

článek v časopise

Jazyk

en

Originální abstrakt

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.

Český abstrakt

Problematika rezistence nádorových buněk k protinádorových léčiv je hlavním problémem v léčbě tohoto závažného onemocnění, a to stále není uspokojivě vysvětlen. Jeho základ spočívá v interakci s cytostatika biomolekul syntetizovaných nádorových buněk. Jedním z obecně uznávaných mechanismů rezistence některých kovů na bázi cytostatik je exprese metalothioneinu v nádorových buňkách. V této studii byla zkoumána elektrochemické profil interakce mezi 23 na síru bohatý fragmenty kovu vazebného proteinu metalothioneinu a cisplatiny. Pro vyhodnocení výsledků byly navrženy interakční konstanty. Zde jsme zjistili, že maximální zvýšení interakce (více než 100%) došlo, když konzervativní aminokyseliny nahrazeny více než jedné poloze mimo cystein clusteru. Naopak, je aminokyselinová substituce v rámci cystein clusteru vedla ke snížení interakce konstanty (až do 10 - 25% z průměru). Tento výsledek jasně ukazuje, že aminokyseliny cysteinu mimo vazebné motivy jsou velmi důležité pro interakce metalothioneinu s cisplatinou. Na základě výsledků lze předpokládat, že nahrazení jednotlivých aminokyselin v peptidového řetězce proteinu výrazně ovlivňuje interakci s cisplatinou, které by mohly být použity pro tvorbu nových typů cytostatik.

Anglický abstrakt

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.

Klíčová slova

aminokyselinové sekvence, interakční studii, Fragmenty metalothioneinu , cisplatina, vysoká propustnost analýza, interakce konstanty

Rok RIV

2013

Vydáno

01.02.2013

Strany od

2625

Strany do

2634

Strany počet

10

BibTex


@article{BUT102365,
  author="Ondřej {Zítka} and Markéta {Komínková} and Sylvie {Skaličková} and Helena {Škutková} and Ivo {Provazník} and Tomáš {Eckschlager} and Marie {Stiborová} and Libuše {Trnková} and Vojtěch {Adam} and René {Kizek}",
  title="Single Amino Acid Change in Metallothionein Metal-Binding Cluster Influences Interaction with Cisplatin",
  annote="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.",
  chapter="102365",
  number="2",
  volume="8",
  year="2013",
  month="february",
  pages="2625--2634",
  type="journal article"
}