Stapled Peptides for Treatment of Cardiovascular Diseases and Inflammation
Posted May 06 2013 8:00pm
Description of Invention: 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.
In vitro data available
In vivo data available (animal)
Inventors: Alan T Remaley (CC) Marcelo A Amar (NHLBI) Imoh Z Ikpot (NHLBI) Denis O Sviridov (NHLBI) David O Osei-Hwedieh (NHLBI)
Collaborative Research Opportunity: The NHLBI Lipoprotein Metabolism Section is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize Hydrocarbon-stapled Apolipoprotein Peptide Mimetics for the Treatment of Cardiovascular Diseases and Inflammation. For collaboration opportunities, please contact Denise Crooks, Ph.D. at firstname.lastname@example.org .