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Peptides having reduced toxicity that stimulate cholesterol efflux

Patent ·
OSTI ID:1463293
; ;
The present invention provides a family of non-naturally occurring polypeptides having cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABCA1 that parallels that of full-length apolipoproteins. Further, the peptides of the invention have little or no toxicity when administered at therapeutic and higher doses. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, and methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia, or inflammation; or diseases involving abnormal glucose metabolism, e.g., diabetes, metabolic syndrome; or Alzheimer's Disease or frontotemporal dementia.
Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE
DOE Contract Number:
AC02-05CH11231
Assignee:
The Regents of the University of California (Oakland, CA)
Patent Number(s):
10,017,551
Application Number:
14/774,682
OSTI ID:
1463293
Country of Publication:
United States
Language:
English

References (13)

Sustained-delivery of an apolipoproteinE–peptidomimetic using multivesicular liposomes lowers serum cholesterol levels journal February 2002
Computational Complexity, Protein Structure Prediction, and the Levinthal Paradox book January 1994
A new HDL mimetic peptide that stimulates cellular cholesterol efflux with high efficiency greatly reduces atherosclerosis in mice journal January 2010
Retention of α-helical structure by HDL mimetic peptide ATI-5261 upon extensive dilution represents an important determinant for stimulating ABCA1 cholesterol efflux with high efficiency journal November 2013
Apolipoprotein E: phospholipid binding studies with synthetic peptides from the carboxyl terminus journal February 1992
The Positional Specificity of EXXK Motifs within an Amphipathic α-Helix Dictates Preferential Lysine Modification by Acrolein: Implications for the Design of High-Density Lipoprotein Mimetic Peptides journal July 2012
Regulation and Mechanisms of ATP-Binding Cassette Transporter A1-Mediated Cellular Cholesterol Efflux journal July 2003
The complete genome sequence of Moorella thermoacetica (f. Clostridium thermoaceticum) journal July 2008
Characteristics of the amino acids as components of a peptide hormone sequence book January 1976
The C-Terminal Lipid-Binding Domain of Apolipoprotein E Is a Highly Efficient Mediator of ABCA1-Dependent Cholesterol Efflux that Promotes the Assembly of High-Density Lipoproteins journal March 2007
Effects of l- or d-Pro incorporation into hydrophobic or hydrophilic helix face of amphipathic α-helical model peptide on structure and cell selectivity journal February 2004
Limits of Cooperativity in a Structurally Modular Protein: Response of the Notch Ankyrin Domain to Analogous Alanine Substitutions in Each Repeat journal November 2002
Protein Folding: A Glimpse of the Holy Grail? journal October 1998

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES