skip to main content
DOE Patents title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: 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 Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1463293
Patent Number(s):
10,017,551
Application Number:
14/774,682
Assignee:
The Regents of the University of California (Oakland, CA)
DOE Contract Number:  
AC02-05CH11231
Resource Type:
Patent
Resource Relation:
Patent File Date: 2014 Mar 14
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES

Citation Formats

Bielicki, John K., Johansson, Jan, and Danho, Waleed. Peptides having reduced toxicity that stimulate cholesterol efflux. United States: N. p., 2018. 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/1463293.
@article{osti_1463293,
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 = {2018},
month = {7}
}

Patent:

Save / Share:

Works referenced in this record:

Protein Folding: A Glimpse of the Holy Grail?
journal, October 1998


A new HDL mimetic peptide that stimulates cellular cholesterol efflux with high efficiency greatly reduces atherosclerosis in mice
journal, January 2010

  • Bielicki, John K.; Zhang, Haiyan; Cortez, Yuan
  • Journal of Lipid Research, Vol. 51, Issue 6, p. 1496-1503
  • DOI: 10.1194/jlr.M003665

Limits of Cooperativity in a Structurally Modular Protein: Response of the Notch Ankyrin Domain to Analogous Alanine Substitutions in Each Repeat
journal, November 2002


The complete genome sequence of Moorella thermoacetica (f. Clostridium thermoaceticum)
journal, July 2008


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
  • DOI: 10.1016/S0168-3659(01)00552-1

Characteristics of the amino acids as components of a peptide hormone sequence
book, January 1976


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
  • DOI: 10.1016/j.bbrc.2003.12.142

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
  • DOI: 10.1021/bi00119a015

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
  • DOI: 10.1021/bi602407r

Regulation and Mechanisms of ATP-Binding Cassette Transporter A1-Mediated Cellular Cholesterol Efflux
journal, July 2003


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
  • DOI: 10.1016/j.bbrc.2013.10.017