Targeting Nuclear Receptors
Nuclear receptors can bind ligand, leading to a conformational change, homo- or hetero-dimerization, nuclear translocation and DNA binding.
Novel, high-affinity peptides can disrupt this process at multiple pressure points, such as (1) the ligand-binding pocket, (2) the dimerization domain, or (3) DNA binding, leading to inactivation.
Driving Apoptosis of Senolytic Cells
DNA damage, oxidative stress or oncogenic mutations can activate nuclear translocation of p53 and p53 interacting proteins (p53IP), helping to tether p53 onto the transcriptional promoter of pro-senescence protein, p21.
Disruption of this interaction by novel, high-affinity p53-redirecting peptides (p53RP) at one of multiple interaction points (sites 1 or 2) can displace p53 back to the cytoplasm where it can trigger cell death by apoptosis.