Biologically active peptides

1. A method of making a peptide or peptide derivative comprising

an amino acid sequence comprising imfwydcye (SEQ ID NO: 431) or

a variant amino acid sequence comprising one, two, three, four, five or six amino acid substitutions in imfwydcye (SEQ ID NO: 431), said variant amino acid sequence comprising X1X2X3X4X5X6X7X8X9X10, wherein X1, when present, is c, s, y, i, D-Pen, C, t, D-Nva, D-Nle or k; X2 is i, y, w or d; X3 is c or m; X4 is f, t, v or c; X5 is w or c; X6 is y or c; X7 is d, e or f; X8 is c, e, f, y or d; X9 is y or w; and X10 is e or i (SEQ ID NO: 433), the method comprising

(a) coupling the C-terminal amino acid of the peptide to a cleavable linking moiety that is bonded to a solid phase support material, wherein the alpha-amino group of the C-terminal amino acid that is to be coupled bears an Fmoc protecting group;

(b) removing the Fmoc protecting group from the C-terminal amino acid that is coupled to the linking moiety;

(c) successively coupling Fmoc-protecting amino acids to the C-terminal amino acid, with attendant cleavage of the Fmoc protecting group prior to each successive amino acid addition, thereby producing an amino acid sequence bearing side chain protecting groups; and

(d) removing the side chain protecting groups and cleaving the peptide from the solid phase support material.

2. The method of claim 1 , wherein the peptide or peptide derivative comprises an amino acid sequence comprising cimfwydcye (SEQ ID NO: 432).

3. The method of claim 1 , wherein the variant amino acid sequence comprises an amino acid sequence comprising X1X2X3X4wydX8ye, wherein X1, when present, is c, C, D-Pen or s; X2 is i, y or w; X3 is c or m; X4 is f, t, or v; and X8 is c or e (SEQ ID NO: 434).

4. The method of claim 1 , wherein the variant amino acid sequence comprises an amino acid sequence comprising X1X2mX4wydX8ye, wherein X1, when present, is c, C or D-Pen; X2 is i or y; X4 is f, t, or v; and X8 is c or e (SEQ ID NO: 435).

5. The method of claim 1 , wherein peptide or peptide derivative comprises or consists of an amino acid sequence selected from the group consisting of Ac-cimfwydeye-NH 2 (SEQ ID NO: 436), Disulphide-Dimer(Ac-cimfwydeye-NH 2 ) 2 (SEQ ID NO: 437), Ac-TTDS-(cymfwydc)-ye-NH 2 (SEQ ID NO: 438), K-TTDS-(cymfwydc)-ye-NH 2 (SEQ ID NO: 439), Ac-cimtwydcye-NH 2 (SEQ ID NO: 440), Ac-cimvwydcye-NH 2 (SEQ ID NO: 441), cymfwydcye (SEQ ID NO: 442), Ac-(cymfwydc)-yeG-NH 2 (SEQ ID NO: 443), Ac-(D-Pen)imfwydeye-NH 2 (SEQ ID NO: 444), O(CH 2 —CH 2 —O—CH 2 —CO-imfwydeye-NH 2 ) 2 (SEQ ID NO: 445), Pyridine-3,5-(CO-imfwydeye-NH 2 ) 2 (SEQ ID NO: 446), H 2 N-E-TTDS-(cymfwydc)-ye-NH 2 (SEQ ID NO: 447), Ac-(cymfwydc)-yeK (SEQ ID NO: 448), Ac-(cymfwydc)-ye-TTDS-K (SEQ ID NO: 449), Ac-simfwydeye-NH 2 (SEQ ID NO: 450), Ac-simfwydeye-NH 2 (SEQ ID NO: 451), Ac-ydmcwcefyi-NH 2 (SEQ ID NO: 452), Ac-idmccyfywe-NH 2 (SEQ ID NO: 453), Ac-cimfwyddye-NH 2 (SEQ ID NO: 454), Ac-(cymfwydc)-ye (SEQ ID NO: 455), Ac-(cymfwydc)-ye-TTDS-NH 2 (SEQ ID NO: 456), Ac-TTDS-(cymfwydc)-ye-TTDS-NH 2 (SEQ ID NO: 457), K-(cymfwydc)-ye-NH 2 (SEQ ID NO: 458), Ac—K-(cymfwydc)-ye-NH 2 (SEQ ID NO: 459), E-(cymfwydc)-ye-NH 2 (SEQ ID NO: 460), Ac—K-TTDS-(cymfwydc)-ye-NH 2 (SEQ ID NO: 461), Ac-(cymfwydc)-yeK-NH 2 (SEQ ID NO: 462), Ac-(cymfwydc)-ye-TTDS-K—NH 2 (SEQ ID NO: 463), Ac-(cymfwydc)-ye-TTDS-E-NH 2 (SEQ ID NO: 464), Ac-timfwydeye-NH 2 (SEQ ID NO: 465), Ac-(cimfwydc)-ye-NH 2 (SEQ ID NO: 466), Ac-(cymfwydc)-ye-NH 2 (SEQ ID NO: 467), Ac-(cwmfwydc)-ye-NH 2 (SEQ ID NO: 468), Ac-cicfwydcye-NH 2 (SEQ ID NO: 469), Ac-(D-Nva)imfwydeye-NH 2 (SEQ ID NO: 470), Ac-(D-Nle)imfwydeye-NH 2 (SEQ ID NO: 471), Ac-(Cys)imfwydeye-NH 2 (SEQ ID NO: 472), (cymfwydc)-ye-NH 2 (SEQ ID NO: 473), TTDS-(cymfwydc)-ye-TTDS-NH 2 (SEQ ID NO: 474), and Ac-kimfwydeye-NH 2 (SEQ ID NO: 475), wherein TTDS is 4,7,10-trioxa-1,13-tridecanediamine, (D-Pen) is D-penicillamine, (D-Nva) is D-norvaline, (D-Nle) is D-norleucine.