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Identification and characterization of novel protein-derived arginine-rich cell-penetrating peptides.

DIR@IMTECH: CSIR-Institute of Microbial Technology

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Title Identification and characterization of novel protein-derived arginine-rich cell-penetrating peptides.
 
Creator Gautam, Ankur
Sharma, Minakshi
Vir, Pooja
Chaudhary, Kumardeep
Kapoor, Pallavi
Kumar, Rahul
Nath, Samir K
Raghava, G.P.S.
 
Subject QR Microbiology
 
Description Cell-penetrating peptides (CPPs) have proven their potential as an efficient delivery system due to their intrinsic ability to traverse biological membranes and transport various cargoes into the cells. In the present study, we have identified novel natural protein-derived CPPs using an integrated (in silico and experimental) approach. First, using bioinformatics approach, arginine-rich peptide segments were extracted from SwissProt proteins and their cell-penetrating properties were predicted. Finally, eight peptides were selected and their internalization was validated using experimental techniques. Laser scanning confocal microscopy and flow cytometry confirmed that seven out of eight peptides were internalized into live cells with varying efficiencies without significant cytotoxicity. Three peptides have shown higher internalization efficacy than TAT peptide, the most widely used CPP. Among these three peptides, one peptide (P8), derived from voltage-dependent L-type calcium channel subunit alpha-1D, was able to accumulate inside in a variety of cell types very efficiently through a rapid dose-dependent process. Further, experiments involving inhibition with various endocytic inhibitors along with co-localization studies indicate that the uptake mechanism of P8 is macropinocytosis, a fluid-phase endocytosis process. In addition, competitive inhibition with heparin revealed the involvement of cell-surface proteoglycans in P8 uptake. In summary, the present study provides evidence that an integrated in silico and experimental approach is an effective strategy for the identification of novel CPPs and CPPs identified in the present study have promising perspectives for future drug delivery applications.
 
Publisher Elsevier
 
Date 2015-01
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://crdd.osdd.net/open/1648/1/GPSR%202015%2C%2010.1016%40j.ejpb.2014.11.020.pdf
Gautam, Ankur and Sharma, Minakshi and Vir, Pooja and Chaudhary, Kumardeep and Kapoor, Pallavi and Kumar, Rahul and Nath, Samir K and Raghava, G.P.S. (2015) Identification and characterization of novel protein-derived arginine-rich cell-penetrating peptides. European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft für Pharmazeutische Verfahrenstechnik e.V, 89. pp. 93-106. ISSN 1873-3441
 
Relation http://www.sciencedirect.com/science/article/pii/S0939641114003476
http://crdd.osdd.net/open/1648/