Modified gherlin peptides

An isolated or purified antibody which specifically recognizes a peptide-type compound or a pharmaceutically acceptable salt thereof having the amino acid sequence selected from the group consisting of SEQ ID NOs:

• 1, 2, 3, 8, 9, 10, 11, 16, 17, 22, 25, 26, 27, 28, 29, 30 and 31,
• wherein one or two amino acid residues outside of positions 1 to 4 from the amino-terminal of the selected SEQ ID NO:
• may be deleted, and/or wherein one or two amino acid residues outside of positions 1 to 4 from the amino-terminal of the selected SEQ ID NO:
• may be substituted,
• wherein the amino acid residue at position 2 or 3 from the amino-terminal of the selected SEQ ID NO:
• is a modified amino acid selected from
• (i) serine, threonine, tyrosine or oxyproline, in which the side-chain hydroxy group is converted into a group represented by —OCO—Z1, —OCS—Z1 or —O—Z3, or
• (ii) cysteine in which the side-chain mercapto group is converted into —SCO—Z1, —SCS—Z1, —S—Z3 or —S—S—Z8, or
• (iii) lysine or arginine, in which the side-chain amino group is converted into —NH—CO—Z2, —NH—CS—Z2, —N(Z5)(Z6), —NH—CO—NH—Z7 or —NH—CS—NH—Z7, or
• (iv) histidine or tryptophan, in which the side-chain imino group is converted into a group represented by the formula:
• wherein Z1 is hydrogen or a saturated or unsaturated alkyl chain containing 1 to 50 carbon atoms, Z2, Z3, Z4, Z5, Z6, Z7 and Z8 are the same or different and represent hydrogen or a saturated or unsaturated alkyl chain containing 1 to 10 carbon atoms,
• wherein said peptide-type compound or pharmaceutically acceptable salt thereof has an activity of increasing intracellular calcium ion concentration, and
• wherein the isolated or purified antibody specifically recognizes the alkyl chain of the modified amino acid of the selected SEQ ID NO:.

An isolated or purified antibody which specifically recognizes a peptide-type compound or the pharmaceutically acceptable salt thereof having the amino acid sequence selected from the group consisting of SEQ ID NOs:

• 1, 2, 3, 8, 9, 10, 11, 16, 17, 22, 25, 26, 27, 29, 30 and 31, in which the side-chain hydroxy group of the serine at position 3 from the amino-terminal of the amino acid sequence of the selected SEQ ID NO:
• is acylated with n-octanoyl,
• wherein said peptide-type compound or pharmaceutically acceptable salt thereof has an activity of increasing intracellular calcium ion concentration, and
• wherein the isolated or purified antibody specifically recognizes the alkyl chain of the acylated serine residue of the selected SEQ ID NO:.

An isolated or purified antibody which specifically recognizes a peptide-type compound or a pharmaceutically acceptable salt thereof having the amino acid sequence selected from the group consisting of SEQ ID NOs:

• 1, 2, 3, 8, 9, 10, 11, 16, 17, 22, 25, 26, 27, 28, 29, 30 and 31,
• wherein one or two amino acid residues outside of positions 1 to 4 from the amino-terminal of the selected SEQ ID NO:
• may be deleted, and/or wherein one or two amino acid residues outside of positions 1 to 4 from the amino-terminal of the selected SEQ ID NO:
• may be substituted,
• wherein the amino acid residue at position 3 from the amino-terminal of the selected SEQ ID NO:
• is a modified amino acid in which:
• (1) one saturated or unsaturated alkyl chain containing 1 to 35 carbon atoms is introduced at the α carbon atom of the amino acid by an ester, ether, thioether, thioester, amide, carbamide, thiocarbamide or disulfide linkage;
• or
• (2) one saturated or unsaturated alkyl chain containing 1 to 35 carbon atoms is introduced at the α carbon atom of the amino acid by an alkylene group containing 1 to 10 carbon atoms and by an ester, ether, thioether, thioester, amide, carbamide, thiocarbamide or disulfide linkage;
• and
• wherein the amino acid residues at positions 1 to 4 from the amino-terminal of the selected SEQ ID NO:
• have been replaced with the formula A-B—C-D-, in which
• A and B are NH2—(CH2)3CH(CH2OH)—CO—, NH2—(CH2)4—CO—, NH2—C(CH3)2—(CH2)3—CO— or NH2—CH(CH3)—(CH2)2—CH(CH3)—CO—,
• C is serine, homoserine, threonine, cysteine, homocysteine, aspartic acid, glutamic acid, adipic acid, lysine or ornithine, any of which has a functional group modified by an acyl group, an alkyl group, or an aralkyl group, and
• D is an amino acid residue which is hydrophobic, or an amino acid residue having a basic side chain,
• wherein said peptide-type compound or pharmaceutically acceptable salt thereof has an activity of increasing intracellular calcium ion concentration, and
• wherein the isolated or purified antibody specifically recognizes the alkyl chain of the modified amino acid of the selected SEQ ID NO:.

An isolated or purified antibody which specifically recognizes a peptide-type compound or a pharmaceutically acceptable salt thereof having the amino acid sequence selected from the group consisting of SEQ ID NOs:

• 1, 2, 3, 8, 9, 10, 11, 16, 17, 22, 25, 26, 27, 28, 29, 30 and 31,
• wherein one or two amino acid residues outside of positions 1 to 4 from the amino-terminal of the selected SEQ ID NO:
• may be deleted, and/or wherein at least one amino acid residues outside of positions 1 to 4 from the amino-terminal of the selected SEQ ID NO:
• may be substituted,
• wherein the amino acid residue at position 3 from the amino-terminal of the selected SEQ ID NO:
• is a modified amino acid selected from
• (i) serine, threonine, tyrosine or oxyproline, in which the side-chain hydroxy group is converted into a group represented by —OCO—Z1, —OCS—Z1 or —O—Z3, or
• (ii) cysteine in which the side-chain mercapto group is converted into —SCO—Z1, —SCS—Z1, —S—Z3 or —S—S—Z8, or
• (iii) lysine or arginine, in which the side-chain amino group is converted into —NH—CO—Z2, —NH—CS—Z2, —N(Z5)(Z6), —NH—CO—NH—Z7 or —NH—CS—NH—Z7, or
• (iv) histidine or tryptophan, in which the side-chain imino group is converted into a group represented by the formula:
• wherein Z1 is hydrogen or a saturated or unsaturated alkyl chain containing 1 to 50 carbon atoms, Z2, Z3, Z4, Z5, Z6, Z7 and Z8 are the same or different and represent hydrogen or a saturated or unsaturated alkyl chain containing 1 to 10 carbon atoms, wherein the amino acid residues at positions 1 to 4 from the amino-terminal of the selected SEQ ID NO:
• have been replaced with the formula A-B—C-D-, in which
• A and B are NH2—(CH2)3CH(CH2OH)—CO—, NH2—(CH2)4—CO—, NH2—C(CH3)2—(CH2)3—CO— or NH2—CH(CH3)—(CH2)2—CH(CH3)—CO—,
• C is serine, homoserine, threonine, cysteine, homocysteine, aspartic acid, glutamic acid, adipic acid, lysine or ornithine, any of which has a functional group modified by an acyl group, an alkyl group, or an aralkyl group, and
• D is an amino acid residue which is hydrophobic, or an amino acid residue having a basic side chain,
• wherein said peptide-type compound or pharmaceutically acceptable salt thereof has an activity of increasing intracellular calcium ion concentration, and
• wherein the isolated or purified antibody specifically recognizes the alkyl chain of the modified amino acid of the selected SEQ ID NO:.

An isolated or purified antibody which specifically recognizes a peptide-type compound or a pharmaceutically acceptable salt thereof having the amino acid sequence selected from the group consisting of SEQ ID NOs:

• 1, 2, 3, 8, 9, 10, 11, 16, 17, 22, 25, 26, 27, 28, 29, 30 and 31, and having a basic amino acid bound to the carboxyl-terminal of said amino acid sequence,
• wherein one or two amino acid residues outside of positions 1 to 4 from the amino-terminal of the selected SEQ ID NO:
• may be deleted, and/or wherein at least one or two amino acid residues outside of positions 1 to 4 from the amino-terminal of the selected SEQ ID NO:
• may be substituted,
• wherein the amino acid residue at position 2 or 3 from the amino-terminal of the selected SEQ ID NO:
• is a modified amino acid in which:
• (1) one saturated or unsaturated alkyl chain containing 1 to 35 carbon atoms is introduced at the α carbon atom of the amino acid by an ester, ether, thioether, thioester, amide, carbamide, thiocarbamide or disulfide linkage;
• (2) one saturated or unsaturated alkyl chain containing 1 to 35 carbon atoms is introduced at the α carbon atom of the amino acid by an alkylene group containing 1 to 10 carbon atoms and by an ester, ether, thioether, thioester, amide, carbamide, thiocarbamide or disulfide linkage;
• or
• (3) one saturated or unsaturated alkyl chain containing 1 to 35 carbon atoms is introduced at the α carbon atom of the amino acid,
• wherein said peptide-type compound or pharmaceutically acceptable salt thereof has an activity of increasing intracellular calcium ion concentration, and
• wherein the isolated or purified antibody specifically recognizes the alkyl chain of the modified amino acid of the selected SEQ ID NO:.

An isolated or purified antibody which specifically recognizes a peptide-type compound or a pharmaceutically acceptable salt thereof having the amino acid sequence of SEQ ID NO:

• 28, wherein the side-chain hydroxy group of the threonine at position 3 from the amino-terminal of the amino acid sequence of SEQ ID NO:
• 28 is acylated with n-octanoyl,
• wherein said peptide-type compound or pharmaceutically acceptable salt thereof has an activity of increasing intracellular calcium ion concentration, and
• wherein the isolated or purified antibody specifically recognizes the alkyl chain of the acylated threonine residue of SEQ ID NO:
• 28.