Mimotope receptors and inhibitors for platelet-platelet and platelet-endothelium interactions

Abstract

Mimotope receptors and inhibitors employ peptide mimics that mimic the shape and function of natural receptors and ligands, thus providing synthetic binding sites for ligands and receptors. Receptor mimics can be attached to carriers, such as liposomes, to act as synthetic platelets, for example, by providing binding sites for binding to other (natural or synthetic) platelets or to the endothelium. Synthetic platelets would have virtually limitless shelf life and would not require disease screening prior to transfusion, thereby providing a solution to the perpetual platelet shortages, as well as the safety and storage issues associated with natural blood platelets. Mimotope inhibitors (either free-molecule receptors or ligands) can act as antithrombotics by inhibiting platelet-platelet or platelet-endothelium interactions. Ligand mimics are preferably D-peptides that resist proteolytic degradation. Furthermore, these ligand mimics can also be attached to carriers for resisting excretion, thus forming the basis for a new class of antithrombotic drugs.

1 . A mimotope receptor comprising a peptide that mimics the shape and function of a natural receptor, thus providing a synthetic binding site for ligands. 
   
   
       2 . The mimotope receptor as claimed in  claim 1  wherein the peptide is an unattached monovalent receptor mimic that inhibits ligand-receptor interaction. 
   
   
       3 . The mimotope receptor as claimed in  claim 1  wherein the peptide is attached to a carrier to provide a monovalent receptor mimic for inhibiting ligand-receptor interaction. 
   
   
       4 . The mimotope receptor as claimed in  claim 1  wherein a plurality of peptides are attached to a carrier to constitute a multivalent receptor mimic capable of providing a synthetic receptor function. 
   
   
       5 . The mimotope receptor as claimed in  claim 3  wherein the carrier and peptide function as an antithrombotic drug by inhibiting platelet-platelet and platelet-endothelium interactions. 
   
   
       6 . The mimotope receptor as claimed in  claim 4  wherein the carrier and plurality of peptides constitute a synthetic platelet. 
   
   
       7 . A mimotope ligand comprising a peptide that mimics a natural ligand capable of binding to a receptor to thus inhibit ligand-receptor interaction, wherein the peptide is a D-peptide to resist proteolytic degradation. 
   
   
       8 . A mimotope ligand comprising a peptide that mimics a natural ligand capable of binding to a receptor to thus inhibit ligand-receptor interaction, wherein the peptide is attached to a carrier to resist excretion. 
   
   
       9 . The mimotope ligand wherein the carrier is a liposome. 
   
   
       10 . A synthetic platelet comprising:
 a carrier; and   a receptor mimic attached to the carrier, the receptor mimic mimicking a shape and size of a binding site of a natural receptor on a natural platelet.   
   
   
       11 . The synthetic platelet as claimed in  claim 10  wherein the receptor mimic is a peptide mimotope. 
   
   
       12 . The synthetic platelet as claimed in  claim 10  wherein a plurality of peptide mimotopes are attached to the carrier to provide multivalent attachment potentially to a plurality of platelets or other synthetic platelets. 
   
   
       13 . The synthetic platelet as claimed in  claim 10  wherein the carrier is a liposome. 
   
   
       14 . An antithrombotic drug comprising a peptide mimotope capable of inhibiting ligand-receptor interaction. 
   
   
       15 . The antithrombotic drug as claimed in  claim 14  wherein the peptide mimotope is a receptor mimic. 
   
   
       16 . The antithrombotic drug as claimed in  claim 14  wherein the peptide mimotope is a ligand mimic having a D-peptide that resists proteolytic degradation. 
   
   
       17 . The antithrombotic drug as claimed in  claim 14  wherein the peptide mimotope is a ligand mimic attached to a carrier that resists excretion. 
   
   
       18 . The antithrombotic drug as claimed in  claim 14  wherein the peptide mimotope is a ligand mimic attached to a carrier to resist excretion, the peptide mimotope comprising a D-peptide that furthermore resists proteolytic degradation.