| abstract |
Y-receptor agonists, selective for Y2 and Y4 receptors compared to Y1 receptors, suitable for the treatment of, for example, obesity, are (a) PP-folded peptides or PP-folded mimetic peptides that contain (i) C-terminal the amino acid sequence of the Y-receptor recognition represented by -X-Thr-Arg-X-Arg-Tyr-C (= O) NRR, where R and R independently represent hydrogen or C-C1-6 alkyl, X denotes Val, Ile, Leu or Ala, a X denotes Gln or Asn, or its conservatively substituted variant, in which Thr is replaced by His or Asn, and / or Tyr is replaced by Trp or Phe; and / or Arg is substituted for Lys, and (ii) the N-terminal amino acid sequence of the Y-receptor recognition, represented as HN-X-Pro-X- (Glu or Asp) -, where X is absent or denotes an amino acid residue, X is Leu or Ser, or conservative Leu or Ser substitutions, or (b) the specified agonist contains the C-terminal amino acid sequence of the Y-receptor recognition as defined in (i), see above, and the indicated Y-receptor recognition sequence associated with the amphiphilic domain of the amino acid sequence containing at least There is one alpha-helical twist adjacent to the N-terminus of the specified hexapeptide sequence, and the twist is enclosed in a spiral configuration using a covalent intramolecular bond, and, optionally, an N-terminal sequence that begins with the amino acid sequence of the Y-receptor recognition by definition (ii), see above. |