FOXO4-DRI Peptide
Organisms host multiple transcription factor proteins, one such class of transcription factor proteins is the FOXO group, or forkhead family of transcription factor-O,(2) which includes four members namely FOXO1, FOXO3, FOXO4, and FOXO6. The FOXO4 factor is considered to regulate various cell pathways including insulin signaling, and cell cycle progression, and other functions that regulate growth and differentiation.
A synthetic version of the FOXO4 protein is FOXO4-DRI, which was developed to be identical to the endogenously available FOXO4 protein, except for the alteration in its amino acid structure. FOXO4-DRI peptide, also called Proxofim, is an acronym for Forkhead box O transcription factor 4-D-Retro-Inverso peptide.(3) FOXO4-DRI peptide is the same as that of FOXO4 protein, except that the L amino acids in its structure are replaced by D amino acids. As a result of this, FOXO4-DRI peptide may be less susceptible towards the normal clearance mechanism as compared to FOXO4.
The retro inverso peptides (DRI peptides) are linear chains of amino acids, where the sequence is "reversed", reversing the chirality of the structure (i.e., L amino acid structure altered to D amino acid and vice versa). D amino acids represent the mirror image of the naturally occurring L amino acids in the biological proteins. The main potential advantage of exchanging L amino acid with D amino acid is that the latter may be more resistant towards degradation, making the protein structure more durable.
The main focus of FOXO4-DRI peptide research is focused on its potential to prevent the binding of the FOXO4 protein with p53 protein.(4) The p53 protein is an endogenous regulator protein, considered to regulate the progression of the cell cycle, including cell death. When FOXO4 protein binds with p53, it does not appear to allow p53 to bind with DNA, thereby preventing apoptosis and cell death. In the presence of FOXO4-DRI peptide, this process may be inhibited, allowing p53 to bind with DNA and thereby help the cell cycle to continue to death.
FOXO4-DRI peptide is selective in nature and only exert this potential action on cells that have become dysfunctional over time due to aging, known as the senescent cells.(4) As a result of this biological pathway, the functioning of the tissues may be improved, aiding cell growth and differentiation.
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