CGRP peptide antagonists and conjugates

A composition of matter, comprising a CGRP peptide antagonist comprising an amino acid sequence of the formula:

• (SEQ ID NO:
• 1127)
• Xaa1Xaa2Xaa3Xaa4Xaa5Xaa6Xaa7V8Xaa9Xaa10Xaa11L12A13
• G14L15L16S17Xaa18S19G20G21V22Xaa23Xaa24Xaa25Xaa26
• F27V28P29Xaa30Xaa31V32G33Xaa34Xaa35A36Xaa37
• wherein:
• Xaa1, Xaa2, Xaa3 Xaa4, Xaa5, Xaa6, and Xaa7, are each independently absent or a hydrophobic amino acid residue selected from Trp, 1-Nal, 2-Nal, Phe, Tyr, Bip, 4-carboxy-phenylalanine, and 4-Amino-Phe;
• Xaa9 is a Thr, Ser, Ala, Gly, Val, Leu, or Ile residue;
• Xaa10 is a His, Nα-Methyl-His, Lys, Homolysine, Ornithine, or 4-Amino-Phe residue;
• Xaa11 is an Nα-Methyl-Arg, homoarginine, Cit, Nα-Methyl-Cit, Homocitrulline, His, Guf, Lys, Homolysine, Ornithine, or 4-Amino-Phe residue;
• Xaa18 is an Nα-Methyl-Arg, homoarginine, Cit, Nα-Methyl-Cit, Homocitrulline, His, Guf, Lys, Homolysine, Ornithine, or 4-Amino-Phe residue;
• Xaa23 is a Val, Arg, D-Arg, homoarginine, Lys, D-Lys, homolysine, Orn, Dab, Dpr, homocysteine, or 4-Amino-Phe residue;
• Xaa24 is an Arg, D-Arg, Homoarginine, Lys, D-Lys, Homolysine, Orn, Dab, Dpr, Homocysteine, or 4-Amino-Phe residue;
• Xaa25 is an Arg, D-Arg, Homoarginine, Lys, D-Lys, Homolysine, Orn, Dab, Dpr, Homocysteine, or 4-Amino-Phe residue;
• Xaa26 is an Asn, Arg, D-Arg, Homoarginine, Lys, D-Lys, Homolysine, Orn, Dab, Dpr, Homocysteine, or 4-Amino-Phe residue;
• Xaa30 is a Thr, Nα-Methyl-Thr, Ser, or Nα-Methyl-Ser residue;
• Xaa31 is an Asn, Lys, Homolysine, Ornithine, 4-carboxy-phenylalanine, 4-Amino-Phe, beta-glutamic acid, beta-Homoglutamic acid, homoglutamic acid, or Asp residue;
• Xaa34 is an Oic, Pro, Hyp, Tic, D-Tic, D-Pro, Thz, Aib, Sar, or Pip residue;
• Xaa35 is a Phe, D-Phe, Tyr, 1-Nal, 2-Nal, Trp, or Bip residue;
• and
• Xaa37 is a Phe, Tyr, 1-Nal, 2-Nal, Trp, Bip, 4-carboxy-phenylalanine, or 4-Amino-Phe residue.