Peptide pharmaceuticals
View Patent ↗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. A peptide product comprising a surfactant X covalently attached to a peptide, the peptide comprising a linker amino acid U and at least three other amino acids:
wherein X is a 1-alkyl glycoside surfactant:
wherein:
A is a hydrophobic substituted or unsubstituted C 8 -C 20 alkyl group which is attached to a saccharide at the C-1 position of the saccharide via an O- or S-glycosidic bond; and
B is a hydrophilic saccharide group covalently attached to the peptide via a side chain of the linker amino acid U.
2. The peptide product of claim 1 , wherein the hydrophilic group of the surfactant is attached to the peptide via an amide bond.
3. The peptide product of claim 1 , wherein the peptide is an opioid peptide.
4. A pharmaceutical composition comprising a therapeutically effective amount of a peptide product of claim 1 or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier or excipient.
5. A method for improving the pharmaceutical and medicinal behavior of a peptide, thereby improving its duration of action, bioavailability, stability or selectivity, comprising covalent attachment of a surfactant X to the peptide, wherein X is as defined in claim 1 and is covalently attached to a side chain of the peptide, and the peptide comprises at least four amino acid residues.
6. A method of treating pain, comprising administration of a therapeutically effective amount of a peptide product of claim 1 or a pharmaceutically acceptable salt thereof.
7. The peptide product of claim 1 , wherein the saccharide is a monosaccharide, a disaccharide or a polysaccharide.
8. The peptide product of claim 1 , wherein the saccharide is selected from glucose, galactose, mannose, maltose, glucuronic acid, diglucuronic acid, galacturonic acid, mannouronic acid and maltouronic acid.
9. The peptide product of claim 1 , wherein the surfactant X comprises 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, 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, tetradecyl maltoside, 1-dodecyl beta-D-maltoside, 1-decyl beta-D-maltoside, or 1-octyl beta-D-maltoside.