Synthetic Apolipoprotein E Mimicking Polypeptides And Methods Of Use

Abstract

The present invention provides methods for using synthetic apolipoprotein E (ApoE)-mimicking peptides. Also disclosed are provides 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.

1 - 96 . (canceled) 
     
     
         97 . A method of reducing oxidative stress in a subject, comprising:
 administering a synthetic apolipoprotein E-mimicking peptide to the subject, whereby the oxidative stress in the subject is reduced.   
     
     
         98 . The method of  claim 97 , wherein the synthetic apolipoprotein E-mimicking peptide is administered in a pharmaceutical composition comprising the synthetic apolipoprotein E-mimicking peptide and a pharmaceutically acceptable carrier. 
     
     
         99 . The method of  claim 97 , wherein the subject has diabetes. 
     
     
         100 . A method of reducing β-cell apoptosis in a subject, comprising: administering a synthetic apolipoprotein E-mimicking peptide to the subject, whereby β-cell apoptosis in the subject is reduced. 
     
     
         101 . The method of  claim 100 , wherein the synthetic apolipoprotein E-mimicking peptide is administered in a pharmaceutical composition comprising the synthetic apolipoprotein E-mimicking peptide and a pharmaceutically acceptable carrier. 
     
     
         102 . The method of  claim 100 , wherein the subject has diabetes. 
     
     
         103 . The method of  claim 97 , wherein the synthetic apolipoprotein E-mimicking peptide consists of a receptor binding domain of apolipoprotein E and a lipid-associating peptide. 
     
     
         104 . The method of  claim 103 , wherein said receptor binding domain is covalently linked to said lipid-associating peptide. 
     
     
         105 . The method of  claim 103 , wherein the receptor binding domain contains an acetyl group on the N-terminus and the lipid-associating peptide contains an amide group on the C-terminus. 
     
     
         106 . The method of  claim 97 , wherein the synthetic apolipoprotein E-mimicking peptide comprises a sequence selected from the group consisting of SEQ ID NOs: 11-14, 18-57, 60, 61, and 62-103. 
     
     
         107 . The method of  claim 103 , wherein the receptor binding domain peptide comprises a sequence selected from the group consisting of SEQ ID NOs: 1-2, 3, 5-10, 15, and 58. 
     
     
         108 . The method of  claim 103 , wherein the lipid-associating peptide is model class A amphipathic helical peptide 18A. 
     
     
         109 . The method of  claim 108 , wherein said lipid-associating peptide comprises a sequence selected from the group consisting of SEQ ID NOs: 4, 16, 17, and 59. 
     
     
         110 . The method of  claim 100 , wherein the synthetic apolipoprotein E-mimicking peptide consists of a receptor binding domain of apolipoprotein E and a lipid-associating peptide. 
     
     
         111 . The method of  claim 110 , wherein said receptor binding domain is covalently linked to said lipid-associating peptide. 
     
     
         112 . The method of  claim 110 , wherein the receptor binding domain contains an acetyl group on the N-terminus and the lipid-associating peptide contains an amide group on the C-terminus 
     
     
         113 . The method of  claim 100 , wherein the synthetic apolipoprotein E-mimicking peptide comprises a sequence selected from the group consisting of SEQ ID NOs: 11-14, 18-57, 60, 61, and 62-103. 
     
     
         114 . The method of  claim 110 , wherein the receptor binding domain peptide comprises a sequence selected from the group consisting of SEQ ID NOs: 1-2, 3, 5-10, 15, and 58. 
     
     
         115 . The method of  claim 110 , wherein the lipid-associating peptide is model class A amphipathic helical peptide 18A. 
     
     
         116 . The method of  claim 115 , wherein said lipid-associating peptide comprises a sequence selected from the group consisting of SEQ ID NOs: 4, 16, 17, and 59.