We previously showed that the 5A peptide can promote cholesterol efflux by the ABCA1 transporter and reduce atherosclerosis in animal models. The peptide was licensed to KineMed Inc, who received a RAID grant for performing preclinical toxicology studies, which have commenced. We have done additional structure function studies on the 5A peptide and identified 2 key hydrophobic residues in the hinge region of this bi-helical peptide for it to be able to promote cholesterol efflux. Based on this finding, we developed a new membrane solubilization model for how apolipoprotein mimetic peptides interact with membranes and promote cholesterol efflux.

Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2013
Total Cost
$1,065,405
Indirect Cost
Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
City
State
Country
Zip Code
Islam, Rafique M; Pourmousa, Mohsen; Sviridov, Denis et al. (2018) Structural properties of apolipoprotein A-I mimetic peptides that promote ABCA1-dependent cholesterol efflux. Sci Rep 8:2956
Ditiatkovski, Michael; Palsson, Jonatan; Chin-Dusting, Jaye et al. (2017) Apolipoprotein A-I Mimetic Peptides: Discordance Between In Vitro and In Vivo Properties-Brief Report. Arterioscler Thromb Vasc Biol 37:1301-1306
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Karathanasis, Sotirios K; Freeman, Lita A; Gordon, Scott M et al. (2017) The Changing Face of HDL and the Best Way to Measure It. Clin Chem 63:196-210
Wolska, Anna; Dunbar, Richard L; Freeman, Lita A et al. (2017) Apolipoprotein C-II: New findings related to genetics, biochemistry, and role in triglyceride metabolism. Atherosclerosis 267:49-60
Jin, Xueting; Sviridov, Denis; Liu, Ying et al. (2016) ABCA1 (ATP-Binding Cassette Transporter A1) Mediates ApoA-I (Apolipoprotein A-I) and ApoA-I Mimetic Peptide Mobilization of Extracellular Cholesterol Microdomains Deposited by Macrophages. Arterioscler Thromb Vasc Biol 36:2283-2291
Remaley, Alan T (2015) HDL cholesterol/HDL particle ratio: a new measure of HDL function? J Am Coll Cardiol 65:364-6
Sviridov, Dmitri; Remaley, Alan T (2015) High-density lipoprotein mimetics: promises and challenges. Biochem J 472:249-59
Amar, Marcelo J A; Sakurai, Toshihiro; Sakurai-Ikuta, Akiko et al. (2015) A novel apolipoprotein C-II mimetic peptide that activates lipoprotein lipase and decreases serum triglycerides in apolipoprotein E-knockout mice. J Pharmacol Exp Ther 352:227-35

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