Abstract
TD1, a peptide chaperone consisting of the sequence ACSSSPHKHCG, has been shown to facilitate transdermal delivery for protein molecules via either co-administration or the fusion approach. We previously reported that a single TD1 motif, fused to the N-terminus of human epidermal growth factor (hEGF) can significantly enhance the transdermal efficiency of the recombinant EGF protein. In an effort to further increase the transdermal efficiency, we have created EGF fusion proteins harboring dual TD1 motifs: TD1-hEGF-TD1, containing one TD1 motif at both the N- and the Cterminus, and TD1-TD1-hEGF, containing two tandem TD1 motifs at the N-terminus. Both TD1-hEGF-TD1 and TD1- TD1-hEGF proteins, expressed in Escherichia coli and purified to apparent homogeneity, exhibited biological activity similar to unmodified hEGF, as revealed by their relative abilities to stimulate fibroblast growth, promote fibroblast migration, and activate the MAP kinase signaling cascade. On the other hand, both TD1-hEGF-TD1 and TD1-TD1-hEGF proteins exhibited a transdermal efficiency enhancement. The improvement was >5-fold compared to unmodified hEGF and 3-fold over the hEGF fusion protein with only one TD1 motif attached. These findings provided proof-of-concept for improving transdermal delivery of protein actives through rational protein design.
Keywords: Fusion protein, human epidermal growth factor, peptide chaperone, transdermal drug delivery, transdermal peptide.
Related Books
In Vitro Propagation and Secondary Metabolite Production from Medicinal Plants: Current Trends (Part 2)
Micropropagation of Medicinal Plants
Software and Programming Tools in Pharmaceutical Research
Biotechnology and Drug Development for Targeting Human Diseases
In Vitro Propagation and Secondary Metabolite Production from Medicinal Plants: Current Trends (Part 1)
Molecular and Physiological Insights into Plant Stress Tolerance and Applications in Agriculture- Part 2
Micropropagation of Medicinal Plants
Genome Editing in Bacteria (Part 1)
Data Science for Agricultural Innovation and Productivity
Animal Models In Experimental Medicine
27