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Theoretical Design of a New Chimeric Protein for the Treatment of Breast Cancer



Soleimani M1 ; Mahnam K2 ; Mirmohammadsadeghi H1, 3 ; Sadeghialiabadi H3, 4 ; Jahaniannajafabadi A1, 3
Authors
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Authors Affiliations
  1. 1. Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, IR, Iran
  2. 2. Biology Department, Faculty of Sciences, Shahrekord University, Shahrekord, IR, Iran
  3. 3. Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, IR, Iran
  4. 4. Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, IR, Iran

Source: Research in Pharmaceutical Sciences Published:2016

Abstract

p28 and NRC peptides are two anticancer peptides with various mechanisms have shown to be effective against breast cancer. Therefore, it seems that construction of a chimeric protein containing the two peptides might cause synergistic cytotoxic effects. However, since the two peptides bear opposite charges, production of a chimeric protein in which the two moieties do not intervene each other is difficult. In this study, our goal was to find a suitable peptide linker for the new chimeric protein in a manner that none of the peptides intervene the other's function. We selected some linkers with different characteristics and lengths and created a small library of the chimeric proteins harboring these linkers. Homology modeling and molecular dynamic simulation revealed that (PA)5 P and (EAAAK)3 linkers can separate the p28 and NRC peptides effectively. Thus, the chimeric protein linked with (PA)5 P or (EAAAK)3 linkers might show synergistic and stronger anticancer effects than the separate peptide moieties because they could exert their cytotoxic effects freely which is not influenced by the other part.
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