Synthetic antibody mimic peptides

Abstract

The present disclosure relates to compositions and methods comprising peptide molecules that mimic the binding and functional properties of native antibodies relative to their respective targets. Some embodiments comprise peptide-drug conjugates (PDCs) comprising the mimic peptides disclosed herein. The targets of these mimic peptides include epidermal growth factor receptor (EGFR), and human epidermal growth factor receptor 2 (HER2), vascular endothelial growth factor (VEGF), programmed cell death protein 1 (PD-1), and programmed death-ligand 1 (PD-L1). The present disclosure comprises application of the knob-socket computational model to design antibody mimics for proteins.

What is claimed is: 
     
         1 . An isolated antibody mimic peptide comprising at least one of a motif sequence WX1EX2PX3FYX4YX5A (SEQ ID NO: 78) or the reverse of said motif sequence, said motif sequence having N amino acids, wherein the length of said motif sequence ranges from 7 to 25 amino acids; wherein P is at amino acid position N/2 of the motif sequence or next thereto; wherein each of X1, X2, X3, X4, and X5 is any of 0 to 8 amino acids, and wherein the FY in the motif sequence can be replaced with YW, YL, YI, YV, YF, WY, LY, IY, VY, YY, TYY, TYW, TYL, TYI, TYV, TYF, TWY, TLY, TIY, TVY, or TFY. 
     
     
         2 . The antibody mimic peptide of  claim 1 , wherein the X1 is SG. 
     
     
         3 . The antibody mimic peptide of  claim 2 , wherein X2 is NG, 
     
     
         4 . The antibody mimic peptide of  claim 3 , wherein X3 is G, 
     
     
         5 . The antibody mimic peptide of  claim 4 , wherein X4 is D. 
     
     
         6 . An isolated antibody mimic peptide comprising a reverse sequence of SEQ ID NO: 1-22. 
     
     
         7 . The antibody mimic peptide of  claim 1 , wherein said antibody mimic peptide is conjugated to a substance. 
     
     
         8 . The antibody mimic peptide of  claim 2 , wherein said antibody mimic peptide is conjugated to a substance. 
     
     
         9 . The antibody mimic peptide of  claim 3 , wherein said antibody mimic peptide is conjugated to a substance. 
     
     
         10 . The antibody mimic peptide of  claim 4 , wherein said antibody mimic peptide is conjugated to a substance. 
     
     
         11 . The antibody mimic peptide of  claim 5 , wherein said antibody mimic peptide is conjugated to a substance. 
     
     
         12 . The antibody mimic peptide of  claim 6 , wherein said antibody mimic peptide is conjugated to a substance. 
     
     
         13 . A pharmaceutical composition comprising the antibody mimic peptide of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         14 . A method for treating a mammal comprising the step of administering to the mammal an effective amount of the composition of  claim 13 . 
     
     
         15 . A kit for diagnosing a disease comprising an antibody mimic peptide of  claim 1  binding to EFGR. 
     
     
         16 . A method for designing an antibody mimic peptide of  claim 1  comprising identifying and mapping of a binding surface based on interactions between antibody and epitope; and selecting the amino acids with high interaction frequency to form a peptide. 
     
     
         17 . The method of  claim 16 , wherein the antibody and epitope interaction is based on crystal structure information. 
     
     
         18 . The method of  claim 16 , wherein the peptide is 10-30 amino acids. 
     
     
         19 . The method of  claim 16 , wherein the interaction frequency is determined by binding energy.