Trojan peptide antennapedia
Low biomembrane permeability has conventionally posed an obstacle to the delivery of anticancer polypeptide moieties and has limited their therapeutic value. The demonstration that translocation of peptides across biological membranes can occur not through the classical endocytosis pathway, but through a seemingly energy-free mechanism has unveiled novel possibilities in biomedical research.
‘Trojan horse’ peptides are small proteins or regions of proteins, otherwise called protein transduction domains (PTDs), which have the ability to traverse biological membranes efficiently including the blood-brain barrier in a temperature-, receptor- and transporter-independent fashion. Their tremendous therapeutic potential lies in the fact that the peptides can carry along any pharmaceutical compound (chemicals, proteins, DNA) that is fused onto them, irrespective of its physical properties. One such peptide is the Drosophila homeotic transcription factor ANTENNAPEDIA.
The antennapedia homeodomain is a sequence-specific transcription factor from the organism Drosophila melanogaster. This protein is encoded by the Antennapedia (antp) gene. Antp is a member of a regulatory system that gives cells specific positions on the anterior-posterior axis of the organism. Thus, Antp aids in the control of cell development in the mesothorax segment in Drosophila.
The homeobox domain, or homeodomain, is one that binds DNA through a helix-turn-helix structural motif. Combination of the presently available NMR data with computer modeling provided the preliminary evidence for the presence of this motif in the homeodomain. Proteins that contain a homeobox domain usually play a role in development, and many of these are sequence-specific transcription factors.
The antennapedia homeodomain is 60 amino acid residues long and contains four alpha helices. This motif is similar to those found in prokaryotic repressor proteins.