PEPTIDE PHARMACEUTICALS
Described herein are methods of syntheses and therapeutic uses of covalently modified peptides and/or proteins. The covalently modified peptides and/or proteins allow for improved pharmaceutical properties of peptide and protein-based therapeutics.
1 - 47 . (canceled)
48 . A peptide product comprising a surfactant X covalently attached to a peptide, the peptide comprising a linker amino acid U and at least one other amino acid:
wherein the surfactant X is
wherein:
A is a hydrophobic group which is a substituted or unsubstituted C 1 -C 30 alkyl group, a substituted or unsubstituted alkoxyaryl group, a substituted or unsubstituted aralkyl group, or a steroid nucleus-containing moiety; and
B is a hydrophilic group which is a saccharide and is covalently attached to the peptide via the linker amino acid U;
and wherein the peptide product displays arrestin-biased agonism or antagonism compared to the unmodified peptide not covalently attached to the surfactant X.
49 . The peptide product of claim 48 , wherein the saccharide is a monosaccharide or disaccharide.
50 . The peptide product of claim 49 , wherein the saccharide is glucose, galactose, mannose, melibiose, maltose, sucrose, glucuronic acid, galacturonic acid, mannouronic acid, diglucuronic acid, melibiouronic acid or maltouronic acid.
51 . The peptide product of claim 48 , wherein the hydrophobic group is a substituted or unsubstituted C 8 -C 20 alkyl group.
52 . The peptide product of claim 48 , wherein the surfactant X is a 1-alkyl glycoside.
53 . The peptide product of claim 52 , wherein the 1-alkyl glycoside is 1-eicosyl beta-D-glucuronic acid, 1-octadecyl beta-D-glucuronic acid, 1-hexadecyl beta-D-glucuronic acid, 1-tetradecyl beta-D-glucuronic acid, 1-dodecyl beta-D-glucuronic acid, 1-decyl beta-D-glucuronic acid, 1-octyl beta-D-glucuronic acid, 1-eicosyl beta-D-diglucuronic acid, 1-octadecyl beta-D-diglucuronic acid, 1-hexadecyl beta-D-diglucuronic acid, 1-tetradecyl beta-D-diglucuronic acid, 1-dodecyl beta-D-diglucuronic acid, 1-decyl beta-D-diglucuronic acid, 1-octyl beta-D-diglucuronic acid, 1-eicosyl beta-D-melibiouronic acid, 1-octadecyl beta-D-melibiouronic acid, 1-hexadecyl beta-D-melibiouronic acid, 1-tetradecyl beta-D-melibiouronic acid, 1-dodecyl beta-D-melibiouronic acid, 1-decyl beta-D-melibiouronic acid or 1-octyl beta-D-melibiouronic acid, or functionalized 1-eicosyl beta-D-glucose, 1-octadecyl beta-D-glucose, 1-hexadecyl beta-D-glucose, 1-tetradecyl beta-D-glucose, 1-dodecyl beta-D-glucose, 1-decyl beta-D-glucose, 1-octyl beta-D-glucose, 1-eicosyl beta-D-maltoside, 1-octadecyl beta-D-maltoside, 1-hexadecyl beta-D-maltoside, 1-tetradecyl beta-D-maltoside, 1-dodecyl beta-D-maltoside, 1-decyl beta-D-maltoside, 1-octyl beta-D-maltoside, 1-eicosyl beta-D-melibiose, 1-octadecyl beta-D-melibiose, 1-hexadecyl beta-D-melibiose, 1-tetradecyl beta-D-melibiose, 1-dodecyl beta-D-melibiose, 1-decyl beta-D-melibiose or 1-octyl beta-D-melibiose, or the corresponding alpha-anomer.
54 . The peptide product of claim 48 , wherein the peptide is an opioid peptide, a PTH peptide, a PTHrP peptide, a glucagon peptide or a GLP-1 peptide, each having a native or non-native amino acid sequence or structure.
55 . The peptide product of claim 48 , wherein the saccharide group of the surfactant is attached to the peptide via an amide bond.
56 . A pharmaceutical composition comprising a therapeutically effective amount of a peptide product of claim 48 or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier or excipient.
57 . A method of modulating signal transduction mediated by an arrestin, comprising contacting a cell with a peptide product of claim 48 .
58 . A method of modulating signal transduction mediated by a G protein-coupled receptor (GPCR), comprising contacting a cell with a peptide product of claim 48 .