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
Liu, Zheng; Thacker, Seth G; Fernandez-Castillejo, Sara et al. (2014) Synthesis of cholesterol analogues bearing BODIPY fluorophores by Suzuki or Liebeskind-Srogl cross-coupling and evaluation of their potential for visualization of cholesterol pools. Chembiochem 15:2087-96
Dai, Cuilian; Yao, Xianglan; Vaisman, Boris et al. (2014) The ABCA1 Transporter Attenuates Ovalbumin-induced Neutrophilic Airway Inflammation. Am J Respir Cell Mol Biol :
Vickers, Kasey C; Remaley, Alan T (2014) HDL and cholesterol: life after the divorce? J Lipid Res 55:4-12
Remaley, Alan T (2013) Apolipoprotein A-II: still second fiddle in high-density lipoprotein metabolism? Arterioscler Thromb Vasc Biol 33:166-7
Sviridov, Denis O; Andrianov, Alexander M; Anishchenko, Ivan V et al. (2013) Hydrophobic amino acids in the hinge region of the 5A apolipoprotein mimetic peptide are essential for promoting cholesterol efflux by the ABCA1 transporter. J Pharmacol Exp Ther 344:50-8
Ditiatkovski, Michael; D'Souza, Wilissa; Kesani, Rajitha et al. (2013) An apolipoprotein A-I mimetic peptide designed with a reductionist approach stimulates reverse cholesterol transport and reduces atherosclerosis in mice. PLoS One 8:e68802