Patent classifications
C07K14/6955
RADIOLABELED MELANOCORTIN 1 RECEPTOR-SPECIFIC ALPHA-MELANOCYTE-STIMULATING HORMONE ANALOGUES FOR IMAGING OR THERAPY
A compound is provided comprising a melanocortin 1 receptor (MC1R) targeting peptide (MC1RTP), a radiolabeling group, and a linker joining the MC1RTP to the radiolabeling group. The MC1RTP is linear or cyclized, and comprises a sequence of Formula I or Formula II: Xaa.sup.1-Xaa.sup.2a-Xaa.sup.3-Xaa.sup.4-Xaa.sup.5-Xaa.sup.6-Xaa.sup.7a (I) or Xaa.sup.1-Xaa.sup.2b-Xaa.sup.3-Xaa.sup.4-Xaa.sup.5-Xaa.sup.6-Xaa.sup.7b (II). Xaa.sup.1 is L-/D-Nle, L-/D-Nle, L-/D-Ala, L-/D-Leu, L-/D-Ile, D-Ile, L-/D-Cys, L-/D-Met, L-/D-Phe, L-/D-Trp, L-/D-Val, L-/D-Nal, L-/D-2-Nal, Gly, L-/D-α-aminobutyric acid, L-/D-norvaline, or L-/D-homonorleucine. Xaa.sup.2a and Xaa.sup.7b are L-/D-Cys, L-/D-Asp, L-/D-Glu, L-/D-2-Aad, L-/D-3-Aad, L-/D-Pra, L-/D-Hpg, or L-/D-Bpg. Xaa.sup.2b and Xaa.sup.7a are L-/D-Cys, L-/D-Lys, L-/D-Orn, L-/D-Dab, L-/D-Dap, L-/D-Lys(N.sub.3), L-/D-Orn(N.sub.3), L-/D-Dab(N.sub.3), L-/D-Dap(N.sub.3), L-/D-2-(5′-azidopentyl)alanine, or L-/D-2-(6′-azidohexyl)alanine. Xaa.sup.3 is L-/D-His, Pro, beta-(1,2,3-triazol-4-yl)-L-alanine, beta-(1,2,3-triazol-4-yl)-D-alanine, 1,2,4-triazole-3-alanine, or 1,2,4-triazole-3-D-N alanine. Xaa.sup.4 is L-/D-Phe, L-/D-2-Nal, L-/D-Phe(4-F), L-/D-Phe(4-Cl), L-/D-Phe(4-Br), L-/D-Phe(4-I), L-/D-Phe(4-NH.sub.2), or L-/D-Phe(4-NO.sub.2). Xaa.sup.5 is L-/D-Arg, L-/D-hArg), Leu, L-/D-Agb, or L-/D-Agp. Xaa.sup.6 is L-/D-Trp, L-/D-Phe, L-/D-Trp(5-Br), L-/D-Trp(5-OCH.sub.3), L-/D-Trp(6-F), L-/D-Trp(5-OH) or L-/D-Trp(CHO). One or more amino acid residues of the MC1RTP is alpha N-methylated, wherein 1, 2, 3 or 4 of Xaa.sup.3, Xaa.sup.5, Xaa.sup.6 and Xaa.sup.7a is alpha N-methylated or wherein 1, 2, 3 or 4 of Xaa.sup.3, Xaa.sup.5, Xaa.sup.6 and Xaa.sup.7b is alpha N-methylated. The linker comprises an albumin-binding group.
Radiolabeled melanocortin 1 receptor-specific alpha-melanocyte-stimulating hormone analogues for imaging or therapy
A compound is provided comprising a melanocortin 1 receptor (MC1R) targeting peptide (MC1RTP), a radiolabeling group, and a linker joining the MC1RTP to the radio labeling group. The MC1RTP is linear or cyclized, and comprises a sequence of Formula I or Formula II: Xaa.sup.1-Xaa.sup.2a-Xaa.sup.3-Xaa.sup.4-Xaa.sup.5-Xaa.sup.6-Xaa.sup.7a (I) or Xaa.sup.1-Xaa.sup.2b-Xaa.sup.3-Xaa.sup.4-Xaa.sup.5-Xaa.sup.6-Xaa.sup.7b (II). Xaa.sup.1 is L-/D-Nle, L-/D-Nle, L-/D-Ala, L-/D-Leu, L-/D-Ile, D-Ile, L-/D-Cys, L-/D-Met, L-/D-Phe, L-/D-Trp, L-/D-Val, L-/D-Nal, L-/D-2-Nal, Gly, L-/D-α-aminobutryic acid, L-/D-norvaline, or L-/D-homonorleucine. Xaa.sup.2a and Xaa.sup.7b are L-/D-Cys, L-/D-Asp, L-/D-Glu, L-/D-2-Aad, L-/D-3-Aad, L-/D-Pra, L-/D-Hpg, or L-/D-Bpg. Xaa.sup.2b and Xaa.sup.7a are L-/D-Cys, L-/D-Lys, L-/D-Orn, L-/D-Dab, L-/D-Dap, L-/D-Lys(N.sub.3), L-/D-Orn(N.sub.3), L-/D-Dab(N.sub.3), L-/D-Dap(N.sub.3), L-/D-2-(5′-azidopentyl)alanine, or L-/D-2-(6′-azidohexyl)alanine. Xaa.sup.3 is L-/D-His, Pro, beta-(1,2,3-triazol-4-yl)-L-alanine, beta-(1,2,3-triazol-4-yl)-D-alanine, 1,2,4-triazole-3-alanine, or 1,2,4-triazole-3-D-alanine. Xaa.sup.4 is L-/D-Phe, L-/D-2-Nal, L-/D-Phe(4-F), L-/D-Phe(4-Cl), L-/D-Phe(4-Br), L-/D-Phe(4-I), L-/D-Phe(4-NH2), or L-/D-Phe(4-NO2). Xaa.sup.5 is L-/D-Arg, L-/D-hArg), Leu, L-/D-Agb, or L-/D-Agp. Xaa.sup.6 is L-/D-Trp, L-/D-Phe, L-/D-Trp(5-Br), L-/D-Trp(5-OCH3), L-/D-Trp(6-F), L-/D-Trp(5-OH) or L-/D-Trp(CHO). One or more amino acid residues of the MC1RTP is alpha N-methylated, wherein 1, 2, 3 or 4 of Xaa.sup.3, Xaa.sup.5, Xaa.sup.6 and Xaa.sup.7a is alpha N-methylated or wherein 1, 2, 3 or 4 of Xaa.sup.3, Xaa.sup.5, Xaa.sup.6 and Xaa.sup.7b is alpha N-methylated. The linker comprises an albumin-binding group.
RADIOLABELED MELANOCORTIN 1 RECEPTOR-SPECIFIC ALPHA-MELANOCYTE-STIMULATING HORMONE ANALOGUES FOR IMAGING OR THERAPY
A compound is provided comprising a melanocortin 1 receptor (MC1R) targeting peptide (MC1RTP), a radiolabeling group, and a linker joining the MC1RTP to the radiolabeling group. The MC1RTP is linear or cyclized, and comprises a sequence of Formula I or Formula II: Xaa.sup.1-Xaa.sup.2a-Xaa.sup.3-Xaa.sup.4-Xaa.sup.5-Xaa.sup.6-Xaa.sup.7a (I) or Xaa.sup.1-Xaa.sup.2b-Xaa.sup.3-Xaa.sup.4-Xaa.sup.5-Xaa.sup.6-Xaa.sup.7b (II). Xaa.sup.1 is L-/D-Nle, L-/D-Nle, L-/D-Ala, L-/D-Leu, L-/D-Ile, D-Ile, L-/D-Cys, L-/D-Met, L-/D-Phe, L-/D-Trp, L-/D-Val, L-/D-Nal, L-/D-2-Nal, Gly, L-/D--aminobutryic acid, L-/D-norvaline, or L-/D-homonorleucine. Xaa.sup.2a and Xaa.sup.7b are L-/D-Cys, L-/D-Asp, L-/D-Glu, L-/D-2-Aad, L-/D-3-Aad, L-/D-Pra, L-/D-Hpg, or L-/D-Bpg. Xaa.sup.2b and Xaa.sup.7a are L-/D-Cys, L-/D-Lys, L-/D-Orn, L-/D-Dab, L-/D-Dap, L-/D-Lys(N.sub.3), L-/D-Orn(N.sub.3), L-/D-Dab(N.sub.3), L-/D-Dap(N.sub.3), L-/D-2-(5-azidopentyl)alanine, or L-/D-2-(6-azidohexyl)alanine. Xaa.sup.3 is L-/D-His, Pro, beta-(1,2,3-triazol-4-yl)-L-alanine, beta-(1,2,3-triazol-4-yl)-D-alanine, 1,2,4-triazole-3-alanine, or 1,2,4-triazole-3-D-N alanine. Xaa.sup.4 is L-/D-Phe, L-/D-2-Nal, L-/D-Phe(4-F), L-/D-Phe(4-Cl), L-/D-Phe(4-Br), L-/D-Phe(4-I), L-/D-Phe(4-NH2), or L-/D-Phe(4-NO2). Xaa.sup.5 is L-/D-Arg, L-/D-hArg), Leu, L-/D-Agb, or L-/D-Agp. Xaa.sup.6 is L-/D-Trp, L-/D-Phe, L-/D-Trp(5-Br), L-/D-Trp(5-OCH3), L-/D-Trp(6-F), L-/D-Trp(5-OH) or L-/D-Trp(CHO). One or more amino acid residues of the MC1RTP is alpha N-methylated, wherein 1, 2, 3 or 4 of Xaa.sup.3, Xaa.sup.5, Xaa.sup.6 and Xaa.sup.7a is alpha N-methylated or wherein 1, 2, 3 or 4 of Xaa.sup.3, Xaa.sup.5, Xaa.sup.6 and Xaa.sup.7b is alpha N-methylated. The linker comprises an albumin-binding group.
RADIOLABELED MELANOCORTIN 1 RECEPTOR-SPECIFIC ALPHA-MELANOCYTE-STIMULATING HORMONE ANALOGUES FOR IMAGING OR THERAPY
A compound is provided comprising a melanocortin 1 receptor (MC1R) targeting peptide (MC1RTP), a radiolabeling group, and a linker joining the MC1RTP to the radiolabeling group. The MC1RTP is linear or cyclized, and comprises a sequence of Formula I or Formula II: Xaa.sup.1-Xaa.sup.2a-Xaa.sup.3-Xaa.sup.4-Xaa.sup.5-Xaa.sup.6-Xaa.sup.7a (I) or Xaa.sup.1-Xaa.sup.2b-Xaa.sup.3-Xaa.sup.4-Xaa.sup.5-Xaa.sup.6-Xaa.sup.7b (I). Xaa.sup.1 is L- /D-Nle, L-/D-Nle, L-/D-Ala, L-/D-Leu, L-/D-Ile, D-Ile, L-/D-Cys, L-/D-Met, L-/D-Phe, L-/D-Trp, L-/D-Val, L-/D-Nal, L-/D-2-Nal, Gly, L-/D--aminobutryic acid, L-/D-norvaline, or L-/D-homonorleucine. Xaa.sup.2a and Xaa.sup.7b are L-/D-Cys, L-/D-Asp, L-/D-Glu, L-/D-2-Aad, L-/D-3-Aad, L-/D-Pra, L-/D-Hpg, or L-/D-Bpg. Xaa.sup.2b and Xaa.sup.7a are L-/D-Cys, L-/D-Lys, L-/D-Orn, L-/D-Dab, L-/D-Dap, L-/D-Lys(N.sub.3), L-/D-Om(N.sub.3), L-/D-Dab(N.sub.3), L-/D-Dap(N.sub.3), L-/D-2-(5-azidopentyl)alanine, or L-/D-2-(6-azidohexyl)alanine. Xaa.sup.3 is L-/D-His, Pro, beta-(1,2,3-triazol-4-yl)-L-alanine, beta-(1,2,3-triazol-4-yl)-D-alanine, 1,2,4-triazole-3-alanine, or 1,2,4-triazole-3-D-N alanine. Xaa.sup.4 is L-/D-Phe, L-/D-2-Nal, L-/D-Phe(4-F), L-/D-Phe(4-Cl), L-/D-Phe(4-Br), L-/D-Phe(4-I), L-/D-Phe(4-NH2), or L-/D-Phe(4-NO2). Xaa.sup.5 is L-/D-Arg, L-/D-hArg), Leu, L-/D-Agb, or L-/D-Agp. Xaa.sup.6 is L-/D-Trp, L-/D-Phe, L-/D-Trp(5-Br), L-/D-Trp(5-OCH3), L-/D-Trp(6-F), L-/D-Trp(5-OH) or L-/D-Trp(CHO). One or more amino acid residues of the MC1RTP is alpha N-methylated, wherein 1, 2, 3 or 4 of Xaa.sup.3, Xaa.sup.5, Xaa.sup.6 and Xaa.sup.7a is alpha N-methylated or wherein 1, 2, 3 or 4 of Xaa.sup.3, Xaa.sup.5, Xaa.sup.6 and Xaa.sup.2b is alpha N-methylated. The linker comprises an albumin-binding group.