David Osei-Hwedieh (NHLBI)
Denis Sviridov (NHLBI)
Imoh Ikpot (NHLBI)
Marcelo Amar (NHLBI)
- In vitro data available
- In vivo data available (animal)
The invention is directed to small molecule mimetics of apolipoproteins that have an inter-helical hydrocarbon bond, which stabilizes helix formation.
Apolipoproteins facilitate the transport of lipids and cholesterol in the body. Mimetics of apolipoproteins have been used to treat cholesterol-related disorders. However, these mimetics are susceptible to degradation in biological fluids and as a result, their ability to bind cholesterol becomes diminished over time.
Scientists at NHLBI have devised methods to stabilize and improve the performance of apolipoprotein mimetic peptides, using a modified hydrocarbon chain (“stapled apolipoproteins”). These stapled apolipoproteins are superior to singular apolipoproteins in that they are more resistant to enzymatic degradation and efflux a greater amount of cellular cholesterol.
Stapled apolipoproteins can be used in the treatment of cardiovascular diseases, particularly for treatment of atherosclerosis.
- Treatment of inflammation and cardiovascular diseases, including hyperlipidemia, atherosclerosis, restenosis, and acute coronary syndrome.
- Inclusion in oral, intravenous or transdermal peptide formulations.
- Stapled apolipoproteins are more resistant to proteolysis and display enhanced bioavailability.
- Stapled apolipoproteins are amenable to oral delivery and have increased permeability to the blood brain barrier.