Bioactive peptide

A pharmaceutical composition comprising

• a) a peptide selected from the group consisting of:
• an amino-terminal modified peptide of SEQ ID NO:1 or SEQ ID NO:2 or SEQ ID NO:3, wherein the amino-terminal modification comprises an amino group monosubstituted or disubstituted with a straight or branched C1-C4 alkyl group, an aralkyl group, an acyl group, a straight or branched C1-C6 alkanoyl group,
• a carboxy-terminal modified peptide of SEQ ID NO:1 or SEQ ID NO:2 or SEQ ID NO:3, wherein the carboxy-terminal modification comprises an ester with a C1-C6 alkyl group, an ester with an aralkyl group, an amide with an amine monosubstituted or disubstituted with a straight or branched C1-C4 alkyl group, or an amide with ammonia, and,
• a tyrosine residue modified peptide of SEQ ID NO:1 or SEQ ID NO:2, wherein the tryosine modification comprises a modification having the chemical formula:
• wherein:
• R1 is a straight or branched C1-C6 alkyl group, aralkyl group, or hydrogen atom;
• Ra is a protecting group cleavable in an acidic condition, an alkali metal, an alkaline earth metal, methoxymethyl, 2-tetrahydrofuranyl, 2-tetrahydropyranyl, methyl, or trifluoromethyl;
• R is each independently a straight or branched C1-C6 alkyl group, an aralkyl group, a straight or branched C1-C6 alkoxy group, SH, a straight or branched C1-C6 alkylthio group, CN, NO2, a halogen, NH2, a mono- or di-(C1-C6 lower alkyl)amino, acetamide, acetyl, trifluoromethyl, hydroxy;
• or two adjacent R or adjacent R and ORa are linked to form methylenedioxy or ethylenedioxy,
• s is an integer from 0 to 2;
• and,
• b) a pharmaceutical carrier;
• wherein the pharmaceutical composition is an anxiolytic drug, a sleep-inducing drug, a sleep-enhancing drug, or an antidepressant drug.

An anxiolytic or sleep-enhancing food comprising a peptide selected from the group consisting of:

• an amino-terminal modified peptide of SEQ ID NO:1 or SEQ ID NO:2 or SEQ ID NO:3, wherein the amino-terminal modification comprises an amino group monosubstituted or disubstituted with a straight or branched C1-C4 alkyl group, an aralkyl group, an acyl group, a straight or branched C1-C6 alkanoyl group,
• a carboxy-terminal modified peptide of SEQ ID NO:1 or SEQ ID NO:2 or SEQ ID NO:3, wherein the carboxy-terminal modification comprises an ester with a C1-C6 alkyl group, an ester with an aralkyl group, an amide with an amine monosubstituted or disubstituted with a straight or branched C1-C4 alkyl group, or an amide with ammonia, and,
• a tyrosine residue modified peptide of SEQ ID NO:1 or SEQ ID NO:2, wherein the tryosine modification comprises a modification having the chemical formula:
• wherein:
• R1 is a straight or branched C1-C6 alkyl group, aralkyl group, or hydrogen atom;
• Ra is a protecting group cleavable in an acidic condition, an alkali metal, an alkaline earth metal, methoxymethyl, 2-tetrahydrofuranyl, 2-tetrahydropyranyl, methyl, or trifluoromethyl;
• R is each independently a straight or branched C1-C6 alkyl group, an aralkyl group, a straight or branched C1-C6 alkoxy group, SH, a straight or branched C1-C6 alkylthio group, CN, NO2, a halogen, NH2, a mono- or di-(C1-C6 lower alkyl)amino, acetamide, acetyl, trifluoromethyl, hydroxy;
• or two adjacent R or adjacent R and ORa are linked to form methylenedioxy or ethylenedioxy, and
• s is an integer from 0 to 2.

A method for relieving anxiety or enhancing sleep, comprising orally administering to a subject in need thereof an effective amount of at least one peptide selected from the group consisting of:

• a peptide consisting of the amino acid sequence Val-Tyr-Leu-Pro-Arg (SEQ ID NO:
• 1),
• a peptide consisting of the amino acid sequence Tyr-Leu-Pro-Arg (SEQ ID NO:2),
• a peptide consisting of the amino acid sequence Leu-Pro-Arg (SEQ ID NO:3),
• an amino-terminal modified peptide of SEQ ID NO:1 or SEQ ID NO:2 or SEQ ID NO:3, wherein the amino-terminal modification comprises an amino group monosubstituted or disubstituted with a straight or branched C1-C4 alkyl group, an aralkyl group, an acyl group, a straight or branched C1-C6 alkanoyl group,
• a carboxy-terminal modified peptide of SEQ ID NO:1 or SEQ ID NO:2 or SEQ ID NO:3, wherein the carboxy-terminal modification comprises an ester with a C1-C6 alkyl group, an ester with an aralkyl group, an amide with an amine monosubstituted or disubstituted with a straight or branched C1-C4 alkyl group, or an amide with ammonia, and,
• a tyrosine residue modified peptide of SEQ ID NO:1 or SEQ ID NO:2, wherein the tryosine modification comprises a modification having the chemical formula:
• wherein:
• R1 is a straight or branched C1-C6 alkyl group, aralkyl group, or hydrogen atom;
• Ra is a protecting group cleavable in an acidic condition, an alkali metal, an alkaline earth metal, methoxymethyl, 2-tetrahydrofuranyl, 2-tetrahydropyranyl, methyl, or trifluoromethyl;
• R is each independently a straight or branched C1-C6 alkyl group, an aralkyl group, a straight or branched C1-C6 alkoxy group, SH, a straight or branched C1-C6 alkylthio group, CN, NO2, a halogen, NH2, a mono- or di-(C1-C6 lower alkyl)amino, acetamide, acetyl, trifluoromethyl, hydroxy;
• or two adjacent R or adjacent R and ORa are linked to form methylenedioxy or ethylenedioxy, and
• s is an integer from 0 to 2, wherein the effective amount is a dose of between 0.005 to 100 mg/kg.