G protein peptidomimetics

A G protein peptidomimetic or salt thereof comprising the sequence of formula (VIII):

• (VIII)
• (SEQ ID NO:
• 8)
• RDX8IQRX7HLX6X5X4X3X2X1
• wherein X1 is selected from the group consisting of:
• leucine (L), L-NH2, isoleucine (I), and X1a;
• wherein X1a is selected from alanine analogue, phenylalanine (F), or tryptophan (W),
• wherein the alanine analogue is a molecule resulting from the replacement of at least one hydrogen of an alanine by at least one moiety selected from the group consisting of C6-12cycloalkyl, C6-12aryl, heteroaryl, and C6-12cycloalkenyl;
• each moiety being optionally substituted with one or more substituents each independently selected from OH, halo, C1-6alkyl, C3-12cycloalkyl, C2-6alkenyl, C1-6alkoxy, oxo, ═CH2, amino, mono- or di-C1-6alkylamino, haloC1-6alkyl, or 2 substituents together with the atom to which they are attached may form a C3-12cycloalkyl, C5-12cycloalkenyl, heterocycloalkyl, or C6-12aryl;
• each of the formed C3-12cycloalkyl, C5-12cycloalkenyl, heterocycloalkyl or C6-12aryl may be optionally substituted by one or more C1-6alkyl;
• wherein X2 is selected from the group consisting of:
• leucine (L), isoleucine (I), tyrosine (Y), histidine (H), and X2a,
• wherein X2a is selected from alanine analogue, phenylalanine (F), or tryptophan (W),
• wherein the alanine analogue is a molecule resulting from the replacement of at least one hydrogen of an alanine by at least one moiety selected from the group consisting of C6-12cycloalkyl, C6-12aryl, heteroaryl, and C6-12cycloalkenyl;
• each moiety being optionally substituted with one or more substituents each independently selected from OH, halo, C1-6alkyl, C3-12cycloalkyl, C2-6alkenyl, C1-6alkoxy, oxo, ═CH2, amino, mono- or di-C1-6alkylamino, haloC1-6alkyl, or 2 substituents together with the atom to which they are attached may form a C3-12cycloalkyl, C5-12cycloalkenyl, heterocycloalkyl, or C6-12aryl;
• each of the formed C3-12cycloalkyl, C5-12cycloalkenyl, heterocycloalkyl or C6-12aryl may be optionally substituted by one or more C1-6alkyl;
• wherein X3 is selected from the group consisting of:
• glutamic acid (E), glutamine (Q), homoglutamic acid (hGlu), aspartic acid (D), alanine (A), and X3a,
• wherein X3a is selected from alanine analogue, phenylalanine (F), or tryptophan (W),
• wherein the alanine analogue is a molecule resulting from the replacement of at least one hydrogen of an alanine by at least one moiety selected from the group consisting of C6-12cycloalkyl, C6-12aryl, heteroaryl, and C6-12cycloalkenyl;
• each moiety being optionally substituted with one or more substituents each independently selected from OH, halo, C1-6alkyl, C3-12cycloalkyl, C2-6alkenyl, C1-6alkoxy, oxo, ═CH2, amino, mono- or di-C1-6alkylamino, haloC1-6alkyl, or 2 substituents together with the atom to which they are attached may form a C3-12cycloalkyl, C5-12cycloalkenyl, heterocycloalkyl, or C6-12aryl;
• each the formed C3-12cycloalkyl, C5-12cycloalkenyl, heterocycloalkyl or C6-12aryl may be optionally substituted by one or more C1-6alkyl;
• wherein X4 is selected from the group consisting of:
• tyrosine (Y), 2-naphthalanine (2-Nal), 1-naphthalanine (1-Nal), and X4a,
• wherein X4a is selected from alanine analogue, phenylalanine (F), or tryptophan (W),
• wherein the alanine analogue is a molecule resulting from the replacement of at least one hydrogen of an alanine by at least one moiety selected from the group consisting of C6-12cycloalkyl, C6-12aryl, heteroaryl, and C6-12cycloalkenyl;
• each moiety being optionally substituted with one or more substituents each independently selected from OH, halo, C1-6alkyl, C3-12cycloalkyl, C2-6alkenyl, C1-6alkoxy, oxo, ═CH2, amino, mono- or di-C1-6alkylamino, haloC1-6alkyl, or 2 substituents together with the atom to which they are attached may form a C3-12cycloalkyl, C5-12cycloalkenyl, heterocycloalkyl, or C6-12aryl;
• each of the formed C3-12cycloalkyl, C5-12cycloalkenyl, heterocycloalkyl or C6-12aryl may be optionally substituted by one or more C1-6alkyl;
• wherein the sequence X4X3X2X1(SEQ ID NO:
• 18) is selected from the group consisting of X4X3X2aX1 (SEQ ID NO:
• 133), X4X3X2X1a (SEQ ID NO:134), X4aX3X2X1 (SEQ ID NO:135) and X4X3aX2X1 (SEQ ID NO:136);
• wherein the sequence X4X3X2X1(SEQ ID NO:18) is not YELL (SEQ ID NO:23),
• wherein X5 is selected from the group consisting of:
• glutamine (Q), cysteine (C), olefinic amino acids, amino acids containing a carboxylic acid group side chain, amino acids containing an amine side-chain, amino acid containing an alkynyl side-chain, and amino acids containing an azidated side-chain,
• wherein X6 is selected from the group consisting of:
• arginine (R), C, olefinic amino acids, amino acids containing a carboxylic acid group side chain, amino acids containing an amine side-chain, amino acid containing an alkynyl side-chain, and amino acids containing an azidated side-chain,
• wherein X7 is selected from the group consisting of:
• methionine (M), C, olefinic amino acids, amino acids containing a carboxylic acid group side chain, amino acids containing an amine side-chain, amino acid containing an alkynyl side-chain, and amino acids containing an azidated side-chain, and
• wherein X8 is selected from the group consisting of:
• isoleucine (I), C, olefinic amino acids, amino acids containing a carboxylic acid group side chain, amino acids containing an amine side-chain, amino acid containing an alkynyl side-chain, and amino acids containing an azidated side-chain, and
• optionally wherein the peptidomimetic comprises at least one covalent tether, the covalent tether being formed from the reaction of an amino acid containing an amine side-chain with an amino acid containing a carboxylic acid group side-chain, or from the reaction between two olefinic amino acids, or from the reaction of an amino acid containing an azidated side-chain with an amino acid containing an alkynyl side-chain, or from the reaction between two amino acids each containing a thiol group side-chain, or from the reaction of an olefinic amino acid with an amino acid containing a thiol group side-chain.