PTD-DBM

PTD-DBM is a synthetic cell-permeable peptide (C124H225N61O28S2, about 3,082.6 g/mol) that links a protein transduction domain (PTD) to a Dishevelled-binding motif (DBM). It was developed by the Choi laboratory at Yonsei University as a competitor peptide for the interaction between CXXC-type zinc finger protein 5 (CXXC5) and the Dishevelled (Dvl) protein. CXXC5 binds Dvl and acts as a negative feedback regulator of Wnt/β-catenin signaling, and PTD-DBM was designed to block that binding step so that the feedback loop is disrupted. The transduction domain is what allows the peptide to enter cells.

PTD-DBM in the research literature

In the originating study, overexpression and silencing of CXXC5 in vitro produced differential regulation of β-catenin, α-smooth muscle actin and collagen I, pointing to a role in myofibroblast differentiation and collagen production, and PTD-DBM activated β-catenin and collagen production in vitro by disrupting CXXC5-Dvl binding. CXXC5-deficient mice were used alongside the peptide to examine the pathway in skin.

A follow-up study extended this work to hair-follicle biology. CXXC5 reduced alkaline phosphatase activity and proliferation in cultured dermal papilla cells, and disrupting the CXXC5-Dvl interaction with the competitor peptide activated Wnt/β-catenin signaling and was associated with changes in hair-follicle cycling and follicle neogenesis endpoints in mouse models.