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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Natural and redesigned wasp venom peptides with selective antitumoral activity

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Author(s):
Torres, Marcelo D. T. [1, 2, 3, 4] ; Andrade, Gislaine P. [1] ; Sato, Roseli H. [1] ; Pedron, Cibele N. [1] ; Manieri, Tania M. [1] ; Cerchiaro, Giselle [1] ; Ribeiro, Anderson O. [1] ; de la Fuente-Nunez, Cesar [2, 3, 4] ; Oliveira, Jr., Vani X. [1]
Total Authors: 9
Affiliation:
[1] Univ Fed ABC, Ctr Ciencias Nat & Humanas, BR-09210580 Santo Andre, SP - Brazil
[2] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 - USA
[3] MIT, Elect Res Lab, Dept Biol Engn, Synthet Biol Grp, MIT Synthet Biol Ctr, Cambridge, MA 02139 - USA
[4] Broad Inst MIT & Harvard, Ctr Microbiome Informat & Therapeut, Cambridge, MA 02139 - USA
Total Affiliations: 4
Document type: Journal article
Source: Beilstein Journal of Organic Chemistry; v. 14, p. 1693-1703, JUL 6 2018.
Web of Science Citations: 8
Abstract

About 1 in 8 U.S. women (approximate to 12%) will develop invasive breast cancer over the course of their lifetime. Surgery, chemotherapy, radiotherapy, and hormone manipulation constitute the major treatment options for breast cancer. Here, we show that both a natural antimicrobial peptide (AMP) derived from wasp venom (decoralin, Dec-NH2), and its synthetic variants generated via peptide design, display potent activity against cancer cells. We tested the derivatives at increasing doses and observed anticancer activity at concentrations as low as 12.5 mu mol L-1 for the selective targeting of MCF-7 breast cancer cells. Flow cytometry assays further revealed that treatment with wild-type (WT) peptide Dec-NH2 led to necrosis of MCF-7 cells. Additional atomic force microscopy (AFM) measurements indicated that the roughness of cancer cell membranes increased significantly when treated with lead peptides compared to controls. Biophysical features such as helicity, hydrophobicity, and net positive charge were identified to play an important role in the anticancer activity of the peptides. Indeed, abrupt changes in peptide hydrophobicity and conformational propensity led to peptide inactivation, whereas increasing the net positive charge of peptides enhanced their activity. We present peptide templates with selective activity towards breast cancer cells that leave normal cells unaffected. These templates represent excellent scaffolds for the design of selective anticancer peptide therapeutics. (AU)

FAPESP's process: 14/04507-5 - Biological applications of new antimicrobial peptides
Grantee:Marcelo Der Torossian Torres
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 14/12938-6 - Biologically active peptides against pathogenic micro-organisms
Grantee:Vani Xavier de Oliveira Junior
Support type: Regular Research Grants
FAPESP's process: 14/18527-8 - Phthalocyanines and Naphthalocyanines: synthesis and characterization of amphiphilic macrocyles for photodynamic therapy
Grantee:Anderson Orzari Ribeiro
Support type: Regular Research Grants
FAPESP's process: 16/09652-9 - Biomolecule damage in neural cellular system in metalic and redox inbalance
Grantee:Giselle Cerchiaro
Support type: Regular Research Grants