Peptides having reduced toxicity that stimulate cholesterol efflux
Abstract
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.
- Inventors:
- Issue Date:
- Research Org.:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE; National Institutes of Health (NIH)
- OSTI Identifier:
- 1925053
- Patent Number(s):
- 11434267
- Application Number:
- 17/016,541
- Assignee:
- The Regents of the University of California (Oakland, CA)
- Patent Classifications (CPCs):
-
A - HUMAN NECESSITIES A61 - MEDICAL OR VETERINARY SCIENCE A61K - PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
A - HUMAN NECESSITIES A61 - MEDICAL OR VETERINARY SCIENCE A61P - SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- DOE Contract Number:
- AC02-05CH11231; HL085791
- Resource Type:
- Patent
- Resource Relation:
- Patent File Date: 09/10/2020
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Bielicki, John K., Johansson, Jan, and Danho, Waleed. Peptides having reduced toxicity that stimulate cholesterol efflux. United States: N. p., 2022.
Web.
Bielicki, John K., Johansson, Jan, & Danho, Waleed. Peptides having reduced toxicity that stimulate cholesterol efflux. United States.
Bielicki, John K., Johansson, Jan, and Danho, Waleed. Tue .
"Peptides having reduced toxicity that stimulate cholesterol efflux". United States. https://www.osti.gov/servlets/purl/1925053.
@article{osti_1925053,
title = {Peptides having reduced toxicity that stimulate cholesterol efflux},
author = {Bielicki, John K. and Johansson, Jan and Danho, Waleed},
abstractNote = {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.},
doi = {},
journal = {},
number = ,
volume = ,
place = {United States},
year = {2022},
month = {9}
}
Works referenced in this record:
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
- Zheng, Ying; Patel, Arti B.; Narayanaswami, Vasanthy
- Biochemical and Biophysical Research Communications, Vol. 441, Issue 1, p. 71-76
Characteristics of the amino acids as components of a peptide hormone sequence
book, January 1976
- Rudinger, J.; Parsons, J. A.
- Peptide Hormones, p. 1-7
Diagnosis and treatment of reverse cholesterol transport deficiency-related diseases
patent-application, June 2011
- Johansson, Jan O.
- US Patent Application 12/976024; 20110152112
Peptides Having Reduced Toxicity Thar Stimulate Cholesterol Efflux
patent-application, September 2014
- Bielicki, John K.; Johansson, Jan; Danho, Waleed
- US Patent Application 14/216749; 20140287994
Limitations of Peptide Retro-inverso Isomerization in Molecular Mimicry
journal, April 2010
- Li, Chong; Pazgier, Marzena; Li, Jing
- Journal of Biological Chemistry, Vol. 285, Issue 25
Sustained-delivery of an apolipoproteinE–peptidomimetic using multivesicular liposomes lowers serum cholesterol levels
journal, February 2002
- Ramprasad, Mysore P.; Anantharamaiah, G. M.; Garber, David W.
- Journal of Controlled Release, Vol. 79, Issue 1-3, p. 207-218
Regulation and Mechanisms of ATP-Binding Cassette Transporter A1-Mediated Cellular Cholesterol Efflux
journal, July 2003
- Wang, N.
- Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 23, Issue 7, p. 1178-1184
Stabilized alpha helical peptides and uses thereof
patent-application, November 2005
- Walensky, Loren D.; Korsmeyer, Stanley J.; Korsmeyer, Susan
- US Patent Application 10/981873; 20050250680
Apolipoprotein E and cholesterol in aging and disease in the brain
journal, January 2008
- de Chaves, Elena Posse; Narayanaswami, Vasanthy; Christoffersen, Christina
- Future Lipidology, Vol. 3, Issue 5
Methods and reagents for modulating cholesterol levels
patent-application, March 2004
- Hayden, Michael R.; Wilson, Angela R. Brooks; Pimstone, Simon N.
- US Patent Application 10/617334; 20040058869
Cysteine-containing peptides having antioxidant properties
patent, October 2009
- Bielicki, John K.
- US Patent Document 7,601,802
The complete genome sequence of Moorella thermoacetica (f. Clostridium thermoaceticum)
journal, July 2008
- Pierce, Elizabeth; Xie, Gary; Barabote, Ravi D.
- Environmental Microbiology, Vol. 10, Issue 10, p. 2550-2573
Helical synthetic peptides that stimulate cellular cholesterol efflux
patent, April 2010
- Bielicki, John K.; Natarajan, Pradeep
- US Patent Document 7,691,965
Orally administered peptides synergize statin activity
patent-application, April 2008
- Fogelman, Alan M.; Anantharamaiah, Gattadahalli M.; Navab, Mohamad
- US Patent Application 11/830675; 20080096815
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
- Song, Yun Mi; Yang, Sung-Tae; Lim, Shin Saeng
- Biochemical and Biophysical Research Communications, Vol. 314, Issue 2, p. 615-621
Compositions and methods of use for treating cardiovascular disease
patent-application, September 2008
- Heinecke, Jay W.; Oram, John F.; Oda, Michael N.
- US Patent Application 11/952044; 20080234192
Apolipoprotein E: phospholipid binding studies with synthetic peptides from the carboxyl terminus
journal, February 1992
- Sparrow, James T.; Sparrow, Doris A.; Fernando, Germain
- Biochemistry, Vol. 31, Issue 4, p. 1065-1068
Protein Folding: A Glimpse of the Holy Grail?
journal, October 1998
- Berendsen, H. J. C.
- Science, Vol. 282, Issue 5389, p. 642-643
Helical synthetic peptides that stimulate cellular cholesterol efflux
patent-application, September 2005
- Bielicki, John K.; Natarajan, Pradeep
- US Patent Application 11/014187; 20050202532
Computational Complexity, Protein Structure Prediction, and the Levinthal Paradox
book, January 1994
- Ngo, J. Thomas; Marks, Joe; Karplus, Martin
- The Protein Folding Problem and Tertiary Structure Prediction, p. 433-506
Mediators of reverse cholesterol transport for the treatment of hypercholesterolemia
patent-application, July 2005
- Sircar, Jagadish C.; Alisala, Kashinatham; Nikoulin, Igor
- US Patent Application 10/975157; 20050159362
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
- Vedhachalam, Charulatha; Narayanaswami, Vasanthy; Neto, Nicole
- Biochemistry, Vol. 46, Issue 10, p. 2583-2593
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
- Zheng, Ying; Kim, Sea H.; Patel, Arti B.
- Biochemistry, Vol. 51, Issue 32, p. 6400-6412