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.
Fusion protein, human epidermal growth factor, peptide chaperone, transdermal drug delivery, transdermal peptide.
School of Life Sciences, University of Science and Technology of China, Hefei 230026, PR China.