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How do cell penetrating peptides enter cells?

Grant number: 19/03023-8
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): May 01, 2019
Effective date (End): February 28, 2023
Field of knowledge:Biological Sciences - Biophysics - Biophysics of Processes and Systems
Principal researcher:Iolanda Midea Cuccovia
Grantee:Peter Park
Home Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:13/08166-5 - Interfacial chemistry: drugs, peptides and ezymes interactions with membrane models, AP.TEM
Associated scholarship(s):19/26557-8 - Coarse graining analysis of the interaction of antimicrobial and cell penetrating peptides with lipid vesicles, BE.EP.DD

Abstract

Cell Penetrating Peptides (CPP) invade eukaryotic cells without damaging the plasma membrane. TAT, a widely used CPP, is an intracellular carrier of drugs, proteins and DNA. The CPP penetration mechanism into cells, despite their increasing use, is controversial. Experimental and theoretical findings diverge; a group of authors propose that penetration depends on classic mechanisms such as endocytosis while others propose penetration through direct translocation with no energy need. The elucidation of the penetration mechanism will provide new insights on the understanding of protein/peptide-membrane interactions, as well as contribute to enhance the efficacy and selectivity of the use of TAT as an intracellular transporter. By employing experimental approaches and Molecular Dynamics simulations, this project aims to study the detailed molecular mechanism of action of TAT. TAT analogues with hydrophobic tails will also be used to study the role of hydrophobicity on the interaction of TAT with membranes. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
FRANCO, LEANDRO R.; PARK, PETER; CHAIMOVICH, HERNAN; COUTINHO, KALINE; CUCCOVIA, IOLANDA M.; LIMA, FILIPE S.. imulations reveal that antimicrobial BP100 induces local membrane thinning, slows lipid dynamics and favors water penetratio. RSC ADVANCES, v. 12, n. 8, p. 4573-4588, . (14/50983-3, 13/08166-5, 19/03023-8)

Please report errors in scientific publications list by writing to: cdi@fapesp.br.