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Protein & Peptide Letters
ISSN (Print): 0929-8665
ISSN (Online): 1875-5305
Epub Abstract Ahead of Print
DOI: 10.2174/0929866521666131224110314      Price:  $95

Enhanced Transdermal Delivery of Epidermal Growth Factor Facilitated by Dual Peptide Chaperone Motifs

Author(s): Jin Pei-pei, Li Fen-fen, Ruan Ren-quan, Li Zhang, Na Man, Yi Hu, Wei Zhou and Wen Long-ping
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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-EGF-TD1, containing one TD1 motif at both the N- and the C-terminus, and TD1-TD1-EGF, containing two tandem TD1 motifs at the N-terminus. Both TD1-EGF-TD1 and TD1-TD1-EGF proteins, expressed in Escherichia coli and purified to apparent homogeneity, exhibited biological activity similar to unmodified EGF, 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-EGF-TD1 and TD1-TD1-EGF proteins exhibited a transdermal efficiency enhancement. The improvement was >5-fold compared to unmodified EGF and 3-fold over the EGF 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
School of Life Sciences, University of Science and Technology of China, Hefei 230026, PR China