Application of Cell Penetrating Peptides for Intracellular Delivery of Endostatin: A Computational Approach


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Abstract

Background:Endostatin is an antiangiogenic compound with anticancer activity. The poor stability and low half-life of endostatin are the main barriers to the clinical use of this protein. Cell-penetrating peptides (CPPs) are extensively applied as carrier in the delivery of drugs and different therapeutic agents. Therefore, they can be proper candidates to improve endostatin delivery to the target cells.

Objective:In this study, we aim to computationally predict appropriate CPPs for the delivery of endostatin.

Methods:Potential appropriate CPPs for protein delivery were selected based on the literature. The main parameters for detection of best CPP-endostatin fusions, including stability, hydrophobicity, antigenicity, and subcellular localization, were predicted using ProtParam, VaxiJen, and DeepLoc-1.0 servers, respectively. The 3D structures of the best CPP-Endostatin fusions were modeled by the I-TASSER server. The predicted models were validated using PROCHECK, ERRAT, Verify3D and ProSA-Web servers. The best models were visualized by the PyMol molecular graphics system.

Results:Considering the principal parameters in the selection of best CPPs for endostatin delivery, endostatin fusions with four CPPs, including Cyt c-ss-MAP, TP-biot1, MPGα, and DPV1047, high stability and hydrophobicity, no antigenicity and extracellular localization were predicted as the best potential fusions for endostatin delivery. Four CPPs, including Cyt c-ss-MAP, TP-biot1, MPGα, and DPV1047, were predicted as the best potential candidates to improve endostatin delivery.

Conclusion:Application of these CPPs may overcome the limitation of endostatin therapeutic applications, including poor stability and low half-life. Subsequent experimental studies will contribute to verifying these computational results.

About the authors

Mozhdeh Zamani

Autophagy Research Center, Shiraz University of Medical Sciences

Author for correspondence.
Email: info@benthamscience.net

Navid Nezafat

Pharmaceutical Sciences Research Cente, Shiraz University of Medical Sciences

Email: info@benthamscience.net

Pooneh Mokarram

Department of Biochemistry, Autophagy Research Center, School of Medicine, Shiraz University of Medical Sciences

Email: info@benthamscience.net

Behnam Kadkhodaei

Department of Radiation Oncology,, Shiraz University of Medical Sciences

Author for correspondence.
Email: info@benthamscience.net

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