Oxyntomodulin analogs

A peptide analog comprising the structure

• Z1-P-M-Z2
• wherein P is a peptide having the amino acid sequence
• (SEQ ID NO:
• 110)
• HX1QGTFTSDX2SX3YLDX4X5X6AX7DFVQWLX8NTKX9X10
• wherein X1 is a D-serine, α-aminoisobutyric acid (aib), 1-Amino-1-cyclobutane carboxylic acid (Acb) residue, 1-Amino-1-cyclohexane carboxylic acid (Acx);
• alpha-aminobutyric acid (Abu);
• D-alpha-aminobutyric acid (D-Abu);
• Aminovaleric acid (Nva);
• beta-cyclopropyl-alanine (Cpa);
• propargylglycine (Prg);
• Allylglycine (Alg);
• 2-Amino-2-cyclohexyl-propanoic acid (2-Cha);
• D-tertbutylglycine (D-tbg);
• Vinylglycine (Vg);
• 1-Amino-1-cyclopropane carboxylic acid (Acp);
• or 1-Amino-1-cyclopentane carboxylic acid (Acpe) residue;
• X2 is a tyrosine (Y) or lysine (K) residue;
• X3 is serine (S) or lysine (K) residue;
• X4 is serine (S), α-aminoisobutyric acid (aib), or glutamic acid (E) residue;
• X5 is an arginine (R) or glutamic acid (E) residue;
• X6 is an arginine (R) or alanine (A) residue;
• X7 is a glutamine (Q) or lysine (K) residue;
• X8 is a methionine (M), norleucine (Nle), methionine sulfoxide (m), or O-methyl-L-homoserine (o) residue;
• X9 is a gamma glutamic acid (γGlu) residue;
• X10 is a gamma glutamic acid (γGlu) residue or absent;
• Z1 is an optionally present protecting group that, if present, is joined to the N-terminal amino group,
• M is (i) a cysteine residue covalently linked to a cholesterol moiety by a hydrophilic linker, (ii) a lysine residue covalently linked to a lipid moiety by a spacer comprising one or more gamma glutamic acid residues, or (iii) a lipid moiety, wherein M is covalently linked to a C-terminal or internal amino acid of P by a spacer comprising one or more gamma-glutamic acid residues;
• and
• Z2 is an optionally present protecting group that, if present, is joined to the C-terminal carboxy group;
• and pharmaceutically acceptable salts thereof,
• wherein the peptide analog or salt thereof has a pI of less than 6.0 and is a dual GLP-1 receptor agonist and glucagon receptor agonist.