Peptides having reduced toxicity that stimulate cholesterol efflux

Title: Peptides having reduced toxicity that stimulate cholesterol efflux

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 and inflammation.

Inventors:: Bielicki, John K.; Johansson, Jan; Danho, Waleed

Issue Date:: 2016-08-16

OSTI Identifier:: 1298004

Assignee:: The Regents of the University of California (Oakland, CA) LBNL

Patent Number(s):: 9,416,162

Application Number:: 14/216,749

Contract Number:: AC02-05CH11231

Resource Relation:: Patent File Date: 2014 Mar 17

Research Org:: Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

Sponsoring Org:: USDOE

Country of Publication:: United States

Language:: English

Subject:: 60 APPLIED LIFE SCIENCES; 59 BASIC BIOLOGICAL SCIENCES

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Other works cited in this record:

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

Bradley, Christina Marchetti; Barrick, Doug
Journal of Molecular Biology, Vol. 324, Issue 2, p. 373-386
DOI: 10.1016/S0022-2836(02)00945-2

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
DOI: 10.1007/978-1-349-02718-7_1

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

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