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Title: Apolipoprotein A-I mutant proteins having cysteine substitutions and polynucleotides encoding same

Patent ·
OSTI ID:909426

Functional Apolipoprotein A-I mutant proteins, having one or more cysteine substitutions and polynucleotides encoding same, can be used to modulate paraoxonase's arylesterase activity. These ApoA-I mutant proteins can be used as therapeutic agents to combat cardiovascular disease, atherosclerosis, acute phase response and other inflammatory related diseases. The invention also includes modifications and optimizations of the ApoA-I nucleotide sequence for purposes of increasing protein expression and optimization.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE
DOE Contract Number:
AC03-76SF00098
Assignee:
The Regents of the University of California (Oakland, CA)
Patent Number(s):
7,223,726
Application Number:
10/342,965
OSTI ID:
909426
Country of Publication:
United States
Language:
English

References (16)

Hydrolysis of platelet-activating factor by human serum paraoxonase journal February 2001
Characterization of human apolipoprotein A-I expressed in Escherichia coli journal January 1997
Dietary Fat Modulates Serum Paraoxonase 1 Activity in Rats journal October 2000
The replacement of arginine by cysteine at residue 151 in Apolipoprotein A-I produces a phenotype similar to that of Apolipoprotein A-I Milano journal January 1997
Evidence for a paraoxonase-independent inhibition of low-density lipoprotein oxidation by high-density lipoprotein journal December 1997
Human Serum Paraoxonase journal September 1998
Serum Paraoxonase Activity and the Extent of Lipid Peroxidation Are not Affected by Increased Levels of Human Apolipoprotein A-I: Studies in Transgenic Mice journal January 2002
High-density lipoprotein composition and paraoxonase activity in Type I diabetes journal November 2001
Paraoxonase inhibits high-density lipoprotein oxidation and preserves its functions. A possible peroxidative role for paraoxonase. journal April 1998
Serum Paraoxonase After Myocardial Infarction journal February 1999
Recombinant apolipoproteins for the treatment of vascular diseases journal January 1999
Paraoxonase 1 Overexpression in Mice and Its Effect on High-Density Lipoproteins journal January 2002
Apolipoprotein A-I Milano and Apolipoprotein A-I Paris Exhibit an Antioxidant Activity Distinct from That of Wild-Type Apolipoprotein A-I journal February 2002
Cysteine Substitutions in Apolipoprotein A-I Primary Structure Modulate Paraoxonase Activity journal February 2001
Subjects With ApoA-I(Lys 107 →0) Exhibit Enhanced Fractional Catabolic Rate of ApoA-I in Lp(AI) and ApoA-II in Lp(AI With AII) journal May 1997
Modulated serum activities and concentrations of paraoxonase in high density lipoprotein deficiency states journal July 1998

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