Human hepatic lipase (hHL) is bound to the cell surface via heparan sulfate proteoglycans
(HPSGs) and hydrolyzes triglycerides and phospholipids within circulating lipoproteins.
High-density lipoprotein (HDL) transports excess extrahepatic cholesterol to the liver for
excretion. However, small lipid-deficient HDL generated by hHL action has the ability to
accept more cholesterol. I hypothesized that a peptide mimicking the cell surface
associations of hHL will displace hHL from cell surfaces, increasing its activity in cell
culture media. To test this hypothesis, I have recombinantly expressed and purified a
tagged mimetic peptide, encompassing the major heparin-binding domain of hHL. Results
from in vitro lipase displacement assays showed that the peptide has an ability to displace
active HPSG associated lipases. Data from proton nuclear magnetic resonance experiments
showed that structural changes occur in the peptide in the presence of heparin. Overall,
these data provide a foundation to use mimetic peptides for the displacement of cell
surface associated lipases
