Beta-arrestin effectors and compositions and methods of use thereof

A peptide or peptide mimetic comprising the sequence of

• a) Xx-Yy-Val-Ww-Zz-Aa-Bb-Cc,
• wherein Xx is selected from the group consisting of null, sarcosine, N-methyl-L-alanine, N-methyl-D-alanine, N,N-dimethylglycine, L-aspartic acid, D-aspartic acid, L-glutamic acid, D-glutamic acid, N-methyl-L-aspartic acid, N-methyl-L-glutamic acid, pyrrolid-1-ylacetic acid, and morpholin-4-ylacetic acid;
• Yy is selected from the group consisting of L-arginine, and L-lysine;
• Ww is selected from the group consisting of L-isoleucine, glycine, L-tyrosine, O-methyl-L-tyrosine, L-valine, L-phenylalanine, 3-hydroxy-L-tyrosine, 2,6-dimethyl-L-tyrosine, 3-fluoro-L-tyrosine, 4-fluorophenyl-L-analine, 2,6-difluoro-L-tyrosine, 3-nitro-L-tyrosine, 3,5-dinitro-L-tyrosine, 3,5-dibromo-L-tyrosine, 3-chloro-L-tyrosine, O-allyl-L-tyrosine, and 3,5-diiodo-L-tyrosine;
• Zz is selected from the group consisting of L-isoleucine, L-valine, L-tyrosine, L-glutamic acid, L-phenylalanine, L-histidine, L-lysine, L-arginine, O-methyl-L-threonine, D-alanine, and L-norvaline;
• Aa is selected from the group consisting of L-histidine, L-histidine-amide, and L-lysine;
• Bb is selected from the group consisting of L-proline, L-proline-amide, D-proline, and D-proline-amide;
• and
• Cc is selected from the group consisting of null, L-isoleucine, L-isoleucine-amide, glycine, glycine-amide, L-alanine, L-alanine-amide, D-alanine, D-phenylalanine, L-norvaline;
• provided that when Xx is L-Aspartic acid, Cc is not L-phenylalanine;
• when Xx is sarcosine, Cc is not L-isoleucine;
• when Ww is glycine, Cc is not glycine;
• when Xx is sarcosine, and Zz is L-valine, Cc is not L-alanine;
• and when Xx is sarcosine, Ww is a L-tyrosine, and Zz is L-isoleucine, Cc is not L-alanine;
• b)
• (SEQ ID NO:
• 4)
• Xx-Arg-Val-Ww-Zz-His-Pro-Cc,
• wherein Xx is selected from the group consisting of sarcosine, N-methyl-L-alanine, N-methyl-D-alanine, N,N-dimethylglycine, L-aspartic acid, D-aspartic acid, L-glutamic acid, D-glutamic acid, N-methyl-L-aspartic acid, N-methyl-L-glutamic acid, pyrrolid-1-ylacetic acid, and morpholin-4-ylacetic acid;
• Ww is selected from the group consisting of L-isoleucine, glycine, L-tyrosine, O-methyl-L-tyrosine, L-valine, L-phenylalanine, 3-hydroxy-L-tyrosine, 2,6-dimethyl-L-tyrosine, 3-fluoro-L-tyrosine, 4-fluorophenyl-L-analine, 2,6-difluoro-L-tyrosine, 3-nitro-L-tyrosine, 3,5-dinitro-L-tyrosine, 3,5-dibromo-L-tyrosine, 3-chloro-L-tyrosine, O-allyl-L-tyrosine, and 3,5-diiodo-L-tyrosine;
• Zz is selected from the group consisting of L-isoleucine, L-valine, L-tyrosine, L-glutamic acid, L-phenylalanine, L-histidine, L-lysine, L-arginine, O-methyl-L-threonine, D-alanine, and L-norvaline;
• and
• Cc is selected from the group consisting of L-isoleucine, L-isoleucine-amide, glycine, glycine-amide, L-alanine, L-alanine-amide, D-alanine, D-phenylalanine, and L-norvaline;
• provided that when Xx is L-Aspartic acid, Cc is not L-phenylalanine;
• when Xx is sarcosine, Cc is not L-isoleucine;
• when Ww is glycine, Cc is not glycine;
• when Xx is sarcosine, and Zz is L-valine, Cc is not L-alanine;
• and when Xx is sarcosine, Ww is a L-tyrosine, and Zz is L-isoleucine, Cc is not L-alanine;
• or
• c) a peptide or peptide mimetic comprising the sequence of
• (SEQ ID NO:
• 17)
• Sar-Arg-Val-Ww-Zz-His-Pro-Cc,
• wherein Ww is selected from the group consisting of L-tyrosine, 3-hydroxy-L-tyrosine, 3-fluoro-L-tyrosine, 2,6-difluoro-L-tyrosine, 3-nitro-L-tyrosine, 3,5-dinitro-L-tyrosine, and 3-chloro-L-tyrosine;
• Zz is selected from the group consisting of L-isoleucine, L-lysine, and O-Methyl-L-threonine;
• and
• Cc is selected from the group consisting of D-alanine, and L-alanine
• provided that when Xx is sarcosine, Ww is a L-tyrosine, and Zz is L-isoleucine, Cc is not L-alanine.