| CPC C07K 14/435 (2013.01) [A61P 3/06 (2018.01); C07K 14/57527 (2013.01); A61K 38/00 (2013.01)] | 10 Claims |
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1. A method of reducing LDL in a patient in need thereof, the method comprising:
administering to the patient in need thereof an effective amount of a calcitonin gene-related peptide (CGRP) receptor antagonist or a pharmaceutically acceptable salt thereof;
wherein the CGRP receptor antagonist is a peptide or a pharmaceutically acceptable salt thereof comprising a structure of Formula I:
X1—Y1—Z1 (I)
wherein:
X1 is a modified N-terminal fragment of CGRP comprising from five to seven amino acid residues, wherein only two amino acid residues of the modified N-terminal fragment are cysteine (Cys), wherein the residue at the C-terminal end of the fragment is Cys, and wherein the residue immediately preceding the C-terminal Cys residue of the fragment is a non-threonine substitution of the threonine (Thr) residue of position 6 of human CGRP;
Y1 is a central core region of CGRP wherein at least one amino acid of the central core is arginine (Arg) or lysine (Lys) and the central core region of CGRP comprises an α-helix; and
Z1 is a modified C-terminal fragment of CGRP comprising from five to seven amino acid residues with a C-terminal amide, where at least one amino acid of the modified C-terminal fragment is phenylalanine (Phe), tyrosine (Tyr), proline (Pro) or hydroxyproline (Hyp).
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