Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters

Database
Language
Journal subject
Publication year range
1.
Chem Res Toxicol ; 27(6): 960-7, 2014 Jun 16.
Article in English | MEDLINE | ID: mdl-24821061

ABSTRACT

The scorpion toxin tamapin displays the most potent and selective blockage against KCa2.2 channels known to date. In this work, we report the biosynthesis, three-dimensional structure, and cytotoxicity on cancer cell lines (Jurkat E6-1 and human mammary breast cancer MDA-MB-231) of recombinant tamapin and five related peptides bearing mutations on residues (R6A,R7A, R13A, R6A-R7A, and GS-tamapin) that were previously suggested to be important for tamapin's activity. The indicated cell lines were used as they constitutively express KCa2.2 channels. The studied toxin-like peptides displayed lethal responses on Jurkat T cells and breast cancer cells; their effect is dose- and time-dependent with IC50 values in the nanomolar range. The order of potency is r-tamapin>GS-tamapin>R6A>R13A>R6A-R7A>R7A for Jurkat T cells and r-tamapin>R7A for MDA-MB-231 breast cancer cells. Our structural determination by NMR demonstrated that r-tamapin preserves the folding of the αKTx5 subfamily and that neither single nor double alanine mutations affect the three-dimensional structure of the wild-type peptide. In contrast, our activity assays show that changes in cytotoxicity are related to the chemical nature of certain residues. Our results suggest that the toxic activity of r-tamapin on Jurkat and breast cancer cells could be mediated by the interaction of charged residues in tamapin with KCa2.2 channels via the apoptotic cell death pathway.


Subject(s)
Neurotoxins/toxicity , Peptides/toxicity , Recombinant Proteins/toxicity , Scorpion Venoms/toxicity , Cell Death/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Jurkat Cells , Lymphocytes/cytology , Lymphocytes/drug effects , Models, Molecular , Neurotoxins/chemistry , Neurotoxins/isolation & purification , Peptides/chemistry , Peptides/isolation & purification , Recombinant Proteins/chemistry , Recombinant Proteins/isolation & purification , Scorpion Venoms/chemistry , Scorpion Venoms/isolation & purification , Structure-Activity Relationship , Tumor Cells, Cultured
SELECTION OF CITATIONS
SEARCH DETAIL