Abstract
Biological membranes are impermeable to almost all compounds having a molecular weight greater than 500 Da. Recently, cell penetrating peptides (CPPs) as delivery vehicles have attracted great interest in the medical sector for the development of novel therapeutic agents or cosmetic products. Herein, a wound healing promoting sequence, namely Tylotoin, was covalently coupled with a cell penetrating peptide to improve the delivery of Tylotoin across cellular membranes. Indeed, internalization studies indicated that the cellular uptake of these novel peptide conjugates into keratinocytes was significantly improved accompanied by good tolerability. In a scratch wound closure assay used to investigate the wound healing capability, the most promising novel peptide chimera (Tylotoin-sC18*) was found to promote the migration of keratinocytes indicating that the fusion to Tylotoin did not cause any loss in its activity. Even more, proliferative effects on keratinocytes were observed, an important step during the wound healing process. Still more encouraging is the capability of Tylotoin-sC18* to exhibit strong antimicrobial activities since the process of wound healing is often affected by bacterial infections. Owing to their multiple functions, the novel peptide chimera may have potential as future agents for the treatment of infected wounds.
Highlights
Efficient wound treatment remains one of the most prevalent healthcare issue as thousands of patients suffer annually from different kinds of skin damage, burns or diseases[1,2,3]
Examples include the delivery of cyclosporine A attached to polyarginine-7 (R7-CsA) across the skin for the treatment of inflammatory skin diseases[10], PEP-1-botulinum neurotoxin A fusion conjugates as cosmetic for treatment of facial wrinkles[11], and more recently, the design of fusion proteins composed of four structural classes of cell penetrating peptides (CPPs) with the human epidermal growth factor as a wound healing agent[12]
We synthesized chimeric peptides consisting of the wound healing promoting peptide Tylotoin[15] and a CPP
Summary
Efficient wound treatment remains one of the most prevalent healthcare issue as thousands of patients suffer annually from different kinds of skin damage, burns or diseases[1,2,3]. Since the skin serves as a protective barrier against external chemical, mechanical, microbial and physical influences[4], it is very challenging to overcome the cellular membrane impermeability In this regard, the discovery of so-called cell penetrating peptides (CPPs) in the last decade has been described as promising approach for the delivery of large molecules across biological membranes[5]. CPPs are relatively short, usually less than 40 amino acids in length, and commonly feature a highly positive net charge Likewise they are able to carry electrostatically or covalently bound biologically active cargoes across cellular membranes including plasmid DNA, siRNA, and therapeutic proteins with high efficiency and low cytotoxicity[6,7]. These novel conjugates were evaluated upon their cytotoxicity towards keratinocytes and a cancer cell line, their cellular internalization behavior and the impact of peptides on in vitro wound healing was investigated
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