Design of a novel cell-permeable chimeric peptide to promote wound healing

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.

Design of CK2β‐Mimicking Peptides as Tools To Study the CK2α/CK2β Interaction in Cancer Cells

“…Notably, the averaged fluorescence intensity measured for CF‐sC18‐I‐Pc was about 900 % higher than for CF‐sC18 (Figure C) which is in accordance with results from microscopic uptake studies (Figures S2A and S2C, respectively). In previous work, we have demonstrated that sC18 as well as a truncated version named sC18* are able to induce and stabilize helix formation, when attached to peptide sequences . The presence of such helical structures is very important for the peptide–lipid interaction at the plasma membrane surface, and thus, these peptide hybrids are often characterized by increased cellular uptake and biological activity in comparison to sC18 alone.…”

Cerebellar Cells Self-Assemble into Functional Organoids on Synthetic, Chemically Crosslinked ECM-Mimicking Peptide Hydrogels

“…The present study aimed to explore synthetic ECM-mimicking hydrogels based on CLP and CLP-RGD blocks conjugated to a poly(ethylene glycol) template (PEG-CLP and PEG-CLP-RGD, respectively), as well as to investigate how these artificial, all-synthetic substrates affect primary cerebellar cell organization, composition, motility and function. Recently, chimeric peptides have emerged as a promising synthetic biological strategy for medical applications [20], and we have already reported the application of PEG-CLP-RGD hydrogels for cancer cell models ( [21], in revision). Additionally, we aimed to elucidate the role of the viscoelasticity of the ECM-mimicking substrate.…”

Newly synthesized peptide, Ara‐27, exhibits significant improvement in cell‐penetrating ability compared to conventional peptides

“…CPP have been combined with a compound such as epidermal growth factor to promote keratinocyte proliferation for skin regeneration or wounds healing by increasing translocation of regenerative compounds into cells. [36][37][38][39] CPP have been combined with BMP2 to promote bone differentiation or to restore bone defects in the bone grafts of dental implants. 40 In addition, CPP-complexes with 41 CPP-SOCS3 complexes have been shown to suppress acute inflammation in multiple.…”