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Molecules 2018, 23(4), 968; https://doi.org/10.3390/molecules23040968

Co-Localization of Crotamine with Internal Membranes and Accentuated Accumulation in Tumor Cells

1
Laboratory of Genetics, Butantan Institute, Sao Paulo 05503-900, Brazil
2
CENTD—Center of Excellence in New Target Discovery, Butantan Institute, Sao Paulo 05503-900, Brazil
3
Biochemistry and Biophysics Laboratory, Butantan Institute, Sao Paulo 05503-900, Brazil
*
Authors to whom correspondence should be addressed.
Academic Editor: Jean-Marc Sabatier
Received: 19 February 2018 / Revised: 29 March 2018 / Accepted: 6 April 2018 / Published: 20 April 2018
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Abstract

Crotamine is a highly cationic; cysteine rich, cross-linked, low molecular mass cell penetrating peptide (CPP) from the venom of the South American rattlesnake. Potential application of crotamine in biomedicine may require its large-scale purification. To overcome difficulties related with the purification of natural crotamine (nCrot) we aimed in the present study to synthesize and characterize a crotamine analog (sCrot) as well investigate its CPP activity. Mass spectrometry analysis demonstrates that sCrot and nCrot have equal molecular mass and biological function—the capacity to induce spastic paralysis in the hind limbs in mice. sCrot CPP activity was evaluated in a wide range of tumor and non-tumor cell tests performed at different time points. We demonstrate that sCrot-Cy3 showed distinct co-localization patterns with intracellular membranes inside the tumor and non-tumor cells. Time-lapse microscopy and quantification of sCrot-Cy3 fluorescence signalss in living tumor versus non-tumor cells revealed a significant statistical difference in the fluorescence intensity observed in tumor cells. These data suggest a possible use of sCrot as a molecular probe for tumor cells, as well as, for the selective delivery of anticancer molecules into these tumors. View Full-Text
Keywords: co-localization; molecular imaging; membrane trafficking; cell penetrating peptide (CPP); crotamine; tumor marker co-localization; molecular imaging; membrane trafficking; cell penetrating peptide (CPP); crotamine; tumor marker
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Mambelli-Lisboa, N.C.; Sciani, J.M.; Brandão Prieto da Silva, A.R.; Kerkis, I. Co-Localization of Crotamine with Internal Membranes and Accentuated Accumulation in Tumor Cells. Molecules 2018, 23, 968.

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