Peptides promoting lipid efflux via abca1 and activating a lipoprotein lipase
AssigneeThe United States of America, as represented by the Secretary, Department of Health and Human Services
InventorsAlan T. Remaley, Marcelo J.A. Amar
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Abstract
Disclosed herein are peptides and peptide analogs with multiple amphipathic α-helical domains that promote lipid efflux from cells via an ABCA1-dependent pathway, as well as peptides that activate lipoprotein lipase, and compositions comprising such peptides or combinations thereof. Also provided herein are methods of using multi-domain amphipathic α-helical peptides or peptide analogs to treat or inhibit dyslipidemic disorders. Methods for identifying non-cytotoxic peptides that promote ABCA1-dependent lipid efflux from cells and activate lipoprotein lipase within cells are also disclosed herein.
Claims25
An isolated peptide or peptide analog, comprising:
- a first domain capable of promoting lipid efflux from cells by an ABCA1-dependent pathway;
- and
- a second domain capable of activating lipoprotein lipase,
- wherein the first domain comprises amino acids 1-18 of any one of SEQ ID NOs:
- 70-75 and the second domain comprises an apoC-II protein, or a variant or fragment thereof which activates lipoprotein lipase thereby promoting lipid efflux without inducing hypertriglyceridemia.
(canceled)
The isolated peptide or peptide analog of claim 8, wherein the additional peptide domain comprises a heparin binding site, an integrin binding site, a P-selectin site, a TAT HIV sequence, a panning sequence, a penatratin sequence, a SAA C-terminus sequence, a SAA N-terminus sequence, a LDL receptor sequence, a modified 18A sequence, an apoA-I Milano sequence, a 6×-His sequence, a lactoferrin sequence, or combinations of two or more thereof.
(canceled)
17-18. (canceled)
A method of treating or inhibiting a dyslipidemic or vascular disorder in a subject, comprising co-administering to the subject a therapeutically effective amount of an isolated peptide or peptide analog comprising an amino acid sequence set forth in any one of SEQ ID NOs:
- 3-45 (which promotes lipid efflux) and an isolated peptide or peptide analog comprising an amino acid sequence set forth in any one of SEQ ID NOs:
- 63-69 (which activates lipoprotein lipase), thereby treating or inhibiting the dyslipidemic or vascular disorder in the subject.
26-27. (canceled)
Dependencies are inferred from the claim text.