MODULATING FOOD INTAKE
The present disclosure relates to a conjugate comprising a PYY peptide or a functional derivative thereof which is coupled to a reactive group. Such a reactive group reacts with albumin so as to form a stable covalent bond therewith. The disclosure further provides methods of reducing water or food intake and reducing food intake between meals by administering such conjugates.
1 . A method of reducing water intake and body weight gain after food deprivation in a subject, comprising: administering to a subject a PYY peptide-albumin conjugate comprising albumin, a PYY peptide or derivative thereof and a maleimido-containing group attached, with or without a linking group, to an amino acid of the PYY peptide to form a modified PYY peptide, wherein the reactive group forms a covalent bond with a thiol of albumin, to thereby reduce water intake and body weight gain in the subject.
2 . The method of claim 1 , wherein the subject has been on a diet of reduced food intake for at least one day up to one month.
3 . The method of claim 1 , wherein the PYY peptide-albumin conjugate is administered before the intake of food after the subject has been on a diet of reduced food intake.
4 . The method of claim 1 , wherein the PYY peptide is PYY 3-36 .
5 . The method of claim 1 , wherein the PYY peptide derivative is PYY 22-36 .
6 . The method of claim 1 , wherein the modified PYY peptide or derivative thereof is selected from SEQ ID NOs: 1-15.
7 . The method of claim 6 , wherein the modified PYY peptide or derivative thereof comprises SEQ ID NO:4, 6, 7, 8, 9, 10, 11, 12 or 13.
8 . The method of claim 1 , wherein the conjugate comprises a linking group and the linking group that attaches to the reactive group and the amino acid of the PYY peptide or derivative thereof is selected from the group consisting of (2-amino)ethoxy acetic acid (AEA), ethylenediamine (EDA), amino ethoxy ethoxy succinimic acid (AEES), 2-[2-(2-amino)ethoxy)]ethoxy acetic acid (AEEA), AEEA-AEEA, —NH.sub.2-(CH 2 ) n —COOH where n is an integer from 1 to 20; one or more alkyl chains (C 1 -C 10 ) saturated or unsaturated which optionally comprises oxygen, nitrogen or sulfur atoms motifs, glycine, 3-aminopropionic acid (APA), 8-aminooctanoic acid (OA), 4-aminobenzoic acid (APhA), and combinations thereof.
9 . The method of claim 1 , wherein the reactive group that forms a covalent bond with the thiol of albumin is selected from gamma-maleimide-butyralamide (GMBA), beta-maleimidopropionic acid (MPA) and alpha-maleimidoacetic acid (MAA).
10 . The method of claim 1 , wherein the subject has a tonicity disorder or condition.
11 . The method of claim 11 , wherein the subject is hypotonic.
12 . The method of claim 1 , wherein the subject is obese.
13 . A method of reducing food intake during periods in between a meal, comprising: administering to a subject a PYY peptide-albumin conjugate comprising albumin, a PYY peptide or derivative thereof and a maleimido-containing group attached, with or without a linking group, to an amino acid of the PYY peptide to form a modified PYY peptide, wherein the reactive group forms a covalent bond with a thiol of albumin, to thereby reduce food intake in between meals by the subject.
14 . The method of claim 13 , wherein the period in between meals during which food intake is reduced is 3 to 8 hours.
15 . The method of claim 13 , wherein the PYY peptide is PYY 3-36 .
16 . The method of claim 13 , wherein the PYY peptide derivative is PYY 22-36 .
17 . The method of claim 13 , wherein the modified PYY peptide or derivative thereof is selected from SEQ ID NOs: 1-15.
18 . The method of claim 17 , wherein the modified PYY peptide or derivative thereof comprises SEQ ID NO:4, 6, 7, 8, 9, 10, 11, 12 or 13.
19 . The method of claim 13 , wherein the conjugate comprises a linking group and the linking group that attaches to the reactive group and the amino acid of the PYY peptide or derivative thereof is selected from the group consisting of (2-amino)ethoxy acetic acid (AEA), ethylenediamine (EDA), amino ethoxy ethoxy succinimic acid (AEES), 2-[2-(2-amino)ethoxy)]ethoxy acetic acid (AEEA), AEEA-AEEA, —NH.sub.2-(CH 2 ) n —COOH where n is an integer from 1 to 20; one or more alkyl chains (C 1 -C 10 ) saturated or unsaturated which optionally comprises oxygen, nitrogen or sulfur atoms motifs, glycine, 3-aminopropionic acid (APA), 8-aminooctanoic acid (OA), 4-aminobenzoic acid (APhA), and combinations thereof.
20 . The method of claim 13 , wherein the reactive group that forms a covalent bond with the thiol of albumin is selected from gamma-maleimide butyralamide (GMBA), betamaleimidopropionic acid (MPA) and alpha-maleimidoacetic acid (MAA).