University of California

The Uab Research Foundation

The University of Alabama

Other

Research, Incorporated

Anji Pharmaceuticals Inc.

Lipimetix Development, LLC

Gattadahalli M Anantharamaiah

Alan M Fogelman

Mohamad Navab

David W Garber

Dennis I Goldberg

Himanshu Gupta

Geeta Datta

Jere P Segrest

C Roger White

Martin Rudolf

Sheila P Handattu

Vinod K Mishra

Dennis Goldberg

Mohammad Navab

Disclosed are synthetic apolipoprotein E-mimicking peptides, derivatives thereof, and related peptides, which are useful as therapeutic agents for reducing plasma cholesterol; synthetic methods of making the peptides; pharmaceutical compositions comprising the peptides, and methods of treating lipid and metabolic disorders using the disclosed synthetic apolipoprotein E-mimicking peptides and compositions thereof. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

APOE mimetic peptides and higher potency to clear plasma cholesterol

ApoE mimetic peptides and higher potency to clear plasma cholesterol

The present invention provides methods for using synthetic apolipoprotein E (ApoE)-mimicking peptides. Also disclosed are methods for using synthetic apolipoprotein E (ApoE)-mimicking peptides to reduce plasma glucose levels. Methods of using the disclosed apolipoprotein E (ApoE)-mimicking peptides to treat diabetes and diabetic complications are also disclosed.

Synthetic apolipoprotein E mimicking polypeptides and methods of use

This invention provides novel active agents (e.g. peptides, small organic molecules, amino acid pairs, etc.) peptides that ameliorate one or more symptoms of eye disease and/or other pathologies characterized by an inflammatory response. In certain embodiment, the peptides resemble a G* amphipathic helix of apolipoprotein J. The agents are highly stable and readily administered via an oral route or via intraocular injection.

Peptides and peptide mimetics to treat pathologies associated with eye disease

The present invention provides novel synthetic apolipoprotein E (ApoE)-mimicking peptides wherein the receptor binding domain of apolipoprotein E is covalently linked to 18A, the well characterized lipid-associating model class A amphipathic helical peptide, or a modified version thereof. Such peptides enhance low density lipoprotein (LDL) and very low density lipoprotein (VLDL) binding to and degradation by fibroblast or HepG2 cells. Also provided are possible applications of the synthetic peptides in lowering human plasma LDL/VLDL cholesterol levels, thus inhibiting atherosclerosis. The present invention also relates to synthetic peptides that can improve HDL function and/or exert anti-inflammatory properties.

This invention provides novel peptides that ameliorate one or more symptoms of atherosclerosis. The peptides are highly stable and readily administered via an oral route. The peptides are effective to stimulate the formation and cycling of pre-beta high density lipoprotein-like particles and/or to promote lipid transport and detoxification. This invention also provides a method of tracking a peptide in a mammal. In addition, the peptides inhibit osteoporosis. When administered with a statin, the peptides enhance the activity of the statin permitting the statin to be used at significantly lower dosages and/or cause the statins to be significantly more anti-inflammatory at any given dose.

Orally administered peptides synergize statin activity

This invention provides novel active agents (e.g. peptides, small organic molecules, amino acid pairs, etc.) peptides that ameliorate one or more symptoms of atherosclerosis and/or other pathologies characterized by an inflammatory response. In certain embodiment, the peptides resemble a G* amphipathic helix of apolipoprotein J. The agents are highly stable and readily administered via an oral route.

Peptides and peptide mimetics to treat pathologies characterized by an inflammatory response

Peptides are provided that ameliorate one or more symptoms of scleroderma. In various embodiments, the peptides range in length from about 10 to about 30 amino acids, comprise a class A amphipathic helix, and bear at least one protecting group. The peptides are highly stable and readily administered via an oral route.

Peptides for treatment of scleroderma

This invention provides novel peptides that ameliorate one or more symptoms of atherosclerosis. The peptides comprise class A amphiphathic helices, are highly stable and readily administered via an oral route. The peptides are effective to stimulate the formation and cycling of pre-beta high density lipoprotein-like particles and/or to promote lipid transport and detoxification.

This invention provides novel peptides that ameliorate one or more symptoms of atherosclerosis. The peptides are class A amphipathic helical peptides. They are highly stable and readily administered via an oral route. The peptides are effective to stimulate the formation and cycling of pre-beta high density lipoprotein-like particles and/or to promote lipid transport and detoxification. This invention also provides a method of tracking a peptide in a mammal. In addition, the peptides inhibit osteoporosis. When administered with a statin, the peptides enhance the activity of the statin permitting the statin to be used at significantly lower dosages and/or cause the statins to be significantly more anti-inflammatory at any given dose.

This invention provides novel peptides that ameliorate one or more symptoms of atherosclerosis. In certain embodiments, the peptides comprise an 18 amino acid class A amphipathic helix with protecting groups on the amino and the carboxyl terminus. The peptides are highly stable, readily administered via an oral route, and effective to stimulate the formation and cycling of pre-beta high density lipoprotein-like particles, and/or to promote lipid transport and detoxification. When administered with a statin, the peptides enhance the activity of the statin permitting the statin to be used at significantly lower dosages and/or cause the statins to be significantly more anti-inflammatory at any given dose.

This invention provides novel peptides that ameliorate one or more symptoms of atherosclerosis. The peptides typically range in length up to about 30 amino acids, comprise at least one class A amphipathic helix, and protect a phospholipid against oxidation by an oxidizing agent. The peptides are highly stable and readily administered via an oral route. The peptides are effective to stimulate the formation and cycling of pre-beta high density lipoprotein-like particles and/or to promote lipid transport and detoxification. In addition, the peptides inhibit osteoporosis. When administered with a statin, the peptides enhance the activity of the statin permitting the statin to be used at significantly lower dosages and/or cause the statins to be significantly more anti-inflammatory at any given dose.

This invention provides novel peptides that ameliorate one or more symptoms of atherosclerosis. The peptides are highly stable and readily administered via an oral route. In addition, the peptides inhibit osteoporosis. When administered with a statin, the peptides enhance the activity of the statin permitting the statin to be used at significantly lower dosages. In certain embodiments, the peptides range in length from about 10 up to about 30 amino acids, comprise at least one class A amphipathic helix, and protect a phospholipid against oxidation by an oxidizing agent.

This invention provides novel peptides for the treatment of atherosclerosis. In certain embodiments the peptide is X-X-X-Xwhere Xand Xare independently selected from the group consisting of alanine (Ala), valine (Val), leucine (Leu), isoleucine (Ile), proline (Pro), phenylalanine (Phe), tryptophan (Trp), methionine (Met), serine (Ser) bearing a hydrophobic protecting group, beta-naphthyl alanine, alpha-naphthyl alanine, norleucine, cyclohexylalanine, threonine (Thr) bearing a hydrophobic protecting group, tyrosine (Tyr) bearing a hydrophobic protecting group, lysine (Lys) bearing a hydrophobic protecting group, arginine (Arg) bearing a hydrophobic protecting group, ornithine (Orn) bearing a hydrophobic protecting group, aspartic acid (Asp) bearing a hydrophobic protecting group, cysteine (Cys) bearing a hydrophobic protecting group, and glutamic acid (Glu) bearing a hydrophobic protecting group; Xand Xare independently selected from the group consisting of Asp, Arg, and Glu; and the peptide converts pro-inflammatory HDL to anti-inflammatory HDL or makes anti-inflammatory HDL more anti-inflammatory.

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Birmingham, AL, United States of America

Gattadahalli M Anantharamaiah