Peptides comprising non-natural amino acids 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 disclosed herein, wherein said analog is optionally modified by one or more active agents. 
     
     
         2 . The composition of  claim 1 , wherein the total number of β-amino acids in the analog is from about 14 percent to about 50 percent of the total number of amino acids of the analog. 
     
     
         3 .- 22 . (canceled) 
     
     
         23 . A method of inhibiting secretion of TNF-α in a subject comprising administering a composition comprising a VIP analog to a subject, wherein said analog comprises an α-amino acid and at least one β-amino acid. 
     
     
         24 . A method of identifying a modulator of human VIP receptor activity comprising:
 a) contacting a human VIP receptor with a VIP analog, wherein said analog comprises an α-amino acid and at least one β-amino acid   b) measuring the association of the VIP analog to the human VIP receptor in the presence and absence of an unknown compound and   c) comparing the rate of association of the VIP analog to the human VIP receptor in the presence of an unknown compound to the rate of association of the VIP analog to the human VIP receptor in the absence of an unknown compound.   
     
     
         25 .- 51 . (canceled) 
     
     
         52 . The composition of  claim 1 , wherein the VIP analog comprises an amino acid sequence selected from the group consisting of: SEQ ID NO: 1, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 19, SEQ ID NO: 20, and SEQ ID NO: 21.