Highly active polypeptides and methods of making and using the same

Abstract

This invention relates to novel compositions comprising analogs of naturally occurring polypeptides, wherein the analog comprises an α-amino acid and at least one β-amino acid. Administration of the compositions may be used for effecting treatment or prevention of a plurality of disease states caused by dysfunctional biochemical or biological pathways. The compositions and methods of this invention are particularly useful to identify novel therapeutic modulators of in-vivo receptor activity with extended half-lives and relevant bioactivity as compared to the naturally translated polypeptides upon which the analogs are derived.

1 . A composition comprising a vasoactive intestinal peptide (VIP) analog, wherein said analog comprises an α-amino acid and at least one β-amino acid. 
     
     
         2 .- 52 . (canceled) 
     
     
         53 . A composition comprising a peptide or a pharmaceutical salt thereof comprising a repetitive pattern of α and β amino acids from the amino-terminus to the carboxy-terminus chosen from: ββαβαααβααβαααβαββ; βαββαααβααβαααβαββ; βααββααβααβαααβααβ; βααβαβαβααβαααβαββ; βααβααββααβαααβαββ; βααβαααββαβαααβαββ; βααβαααβαββαααβααβ; βααβαααβααββααβαββ; βααβαααβααβαβαβαββ; βααβαααβααβααββαββ; βααβαααβααβαααββαβ; and βααβαααβααβαααβαββ; wherein the peptide comprises between about 7% to about 50% β amino acids. 
     
     
         54 . The composition of  claim 53 , wherein the peptide or pharmaceutical salt thereof comprises between about 10 and about 100 residues. 
     
     
         55 . The composition of  claim 53 , wherein at least one β amino acid is a cyclic β amino acid. 
     
     
         56 . The composition of  claim 55 , wherein the cyclic β amino acid is APC or ACPC. 
     
     
         57 . The composition of  claim 53 , wherein the pattern of α and β amino acids repeats at least once. 
     
     
         58 . The composition of  claim 53 , wherein the peptide or pharmaceutical salt thereof comprises an amino acid sequence from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, and SEQ ID NO: 10. 
     
     
         59 . The composition of  claim 53 , further comprising at least one other active agent. 
     
     
         60 . A method of manufacturing the composition of  claim 53  or a pharmaceutical salt derived therefrom comprising catalyzing a reaction between at least one α-amino acid with at least one β-amino acid. 
     
     
         61 . A kit comprising the composition of  claim 53 .