1. A peptide according to formula I
R1\u2014X\u2014X1\u2014X2\u2014X3\u2014X4\u2014X5\u2014X6\u2014X7\u2014X8\u2014X9\u2014X10\u2014X11-R2\u2003\u2003I
wherein R1, which is bonded to an N-terminal NH2-group, is either absent or represents C1-4alkanoyl or R4, which is a protracting group, optionally attached to X via a linker, S;
X represents a bond or an amino acid, a di- or tri-peptide residue, wherein the amino acid(s) may be natural or synthetic;
X1 represents a bond or an amino acid residue with a functional group in the side chain to which a protracting group, R4, may be attached, optionally via a linker, S;
X2 represents a bond or an amino acid, di-, tri- or tetra-peptide residue, wherein the amino acid(s) may be natural or synthetic;
X3 represents a bond or an amino acid residue optionally capable of making a bridge to X10;
X4 represents a bond or an amino acid or di-peptide residue, wherein the amino acid(s) may be natural or synthetic;
X5 represents an amino acid residue selected from His, Ala, Nle, Met, Met(O), Met(O2), Gln, Gln(\u03b5-alkyl), Gln(\u03b5-aryl), Asn, Asn(\u03b5-alkyl), Asn(\u03b5-aryl), Ser, Thr, Cys, F-Pro, Pro, Hyp, (S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, Trp, 1-naphthylalanine, 2-naphthylalanine, 2-pyridylalanine, 3-pyridylalanine, 4-pyridylalanine, 2-thienylalanine, 3-thienylalanine, 4-thiazolylalanine, 2-furylalanine, 3-furylalanine, Phe, wherein the phenyl moiety of said Phe is optionally substituted by halogen, hydroxyl, alkoxy, nitro, benzoyl, methyl, trifluoromethyl or cyano;
X6 represents (D)-Phe, wherein the phenyl moiety of said (D)-Phe is optionally substituted with halogen, hydroxy, alkoxy, nitro, methyl, trifluoromethyl or cyano;
X7 represents Arg;
X8 represents Trp or 2-naphthylalanine;
X9 represents a bond or an amino acid, or di-peptide residue, wherein the amino acid(s) may be natural or synthetic;
X10 represents a bond or an amino acid residue optionally capable of making a bridge to X3;
X11 represents a bond, an amino acid or a di-peptide, wherein the amino acid(s) may be natural or synthetic;
R2 represents \u2014OH or \u2014NRR\u2032, wherein R and R\u2032 independently represent hydrogen, C1-8alkyl, C2-8alkenyl or C2-8alkynyl;
wherein the peptide of formula I is optionally cyclized from X3 to X10 via a lactame or a disulfide bridge;
with the provision that the compound according to formula I comprises one protracting group;
and with the further proviso that compounds of formula I comprises at least 7 amino acid residues;
and any pharmaceutically acceptable salt, solvate or hydrate thereof.
2. The peptide of claim 1, wherein R4 represents a straight, branched andor cyclic C8-22alkanoyl, C8-22alkenoyl or C8-22alkynoyl, all of which may optionally be substituted with one or more substituents selected from hydroxyl, halogen, carboxyl and aryl, wherein said aryl may optionally be further substiututed by one or more substituents selected from hydroxyl, halogen, and carboxyl;
or wherein R4 represents C7-17alkyl-C(O)\u2014NH\u2014S(O)2\u2014C(O)\u2014, wherein said alkyl may be substituted with one or more halogens;
or wherein R4 represents R5\u2014C(O)\u2014NH\u2014S(O)2\u2014(CH2)3\u2014C(O)\u2014, wherein R5 represents 1-(4-benzoylphenyl)ethyl;
or wherein R4 represents a steroid represented by formula II or IIa
wherein each R3 independently represents hydrogen, hydroxyl or R3 together with the bond which binds it to the ring carbon constitute \u2550O;
or wherein R4 represents a structure according to formula II, IIIa, IIIb, IV or IVa
wherein n is 1, 2, or 3;
each mPEG independently represents methoxy polyethylene glycol with a molecular weight between about 2 kDa and about 50 kDa;
each A independently represents hydrogen or C1-4alkyl;
and wherein X3 represents Lys, Orn, 2,4-diamino butyric acid, 2,3-diamino propionic acid, Cys, homoCys, Glu, Asp, Gln or Asn (the skilled artisan will recognize that references to 2,4-diamino butyric acid typically are to be understood as actually referring to the related acid residue\u2014i.e., the acid residue that acts as a bridging group in the peptide);
and wherein X10 represents Lys, Orn, 2,4-diamino butyric acid, 2,3-diamino propionic acid, Cys, homoCys, Glu, Asp, Gln or Asp;
and wherein the linker S if present represents \u03b2-alanine, Glu, Gly-Gln, Gly-Glu, Gly-His, or
y being 1, 2, 3, 4 or 5.
3. The peptide of claim 2, wherein there is a bond between X3 and X10 to make the compound of formula I cyclic by a disulfide bridge (X3, X10 are independently Cys or homoCys) or by an lactam bond between an acid in the side chain of X3 or X10 and an amine in the side chain of X10 or X3.
4. The peptide of claim 3, wherein X is a bond.
5. The peptide of claim 3, wherein X1 represents a bond; X2 represents Nle; or X1 represents a bond and X2 represents Nle.
6. The peptide of claim 4, wherein X1 represents a bond; X2 represents Nle; or X1 represents a bond and X2 represents Nle.
7. The peptide of claim 6, wherein X3 represents Glu or Asp and X10 represents Lys, Orn, 2,4-diamino butyric acid or 2,3-diamino propionic acid.
8. The peptide of claim 3, wherein X3 represents Glu or Asp and X10 represents Lys, Orn, 2,4-diamino butyric acid or 2,3-diamino propionic acid.
9. The peptide of claim 7, wherein X3 represents Glu or Asp, and X10 represents Lys.
10. The peptide of claim 3, wherein X4 represents a bond.
11. The peptide of claim 9, wherein X4 represents a bond.
12. The peptide of claim 3, wherein X5 represents Ala, Nle, Met, Met(O), Met(O2), Gln, Gln(\u03b5-alkyl), Gln(\u03b5-aryl), Asn, Asn (\u03b5-alkyl), Asn(\u03b5-aryl), Ser, Thr, Cys, F-Pro, Pro, Hyp, (S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, Trp, 1-naphthylalanine, 2-naphthylalanine, 2-PyAla, 3-PyAla, 4-PyAla, 2-thienylalanine, 3-thienylalanine, 4-thiazolylalanine, 2-furylalanine, 3-furylalanine, Phe, wherein the phenyl moiety of said Phe is optionally substituted by halogen, hydroxyl, alkoxy, nitro, benzoyl, methyl, trifluoromethyl or cyano.
13. The peptide of claim 11, wherein X5 represents Ala, Nle, Met, Met(O), Met(O2), Gln, Gln(\u03b5-alkyl), Gln(\u03b5-aryl), Asn, Asn (\u03b5-alkyl), Asn(\u03b5-aryl), Ser, Thr, Cys, F-Pro, Pro, Hyp, (S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, Trp, 1-naphthylalanine, 2-naphthylalanine, 2-PyAla, 3-PyAla, 4-PyAla, 2-thienylalanine, 3-thienylalanine, 4-thiazolylalanine, 2-furylalanine, 3-furylalanine, Phe, wherein the phenyl moiety of said Phe is optionally substituted by halogen, hydroxyl, alkoxy, nitro, benzoyl, methyl, trifluoromethyl or cyano.
14. The peptide of claim 3, wherein X5 represents His.
15. The peptide of claim 9, wherein X5 represents His.
16. The peptide of claim 3, wherein X5 represents 3-PyAla, Hyp, Gln or Asn.
17. The peptide of claim 9, wherein X5 represents 3-PyAla, Hyp, Gln or Asn.
18. The peptide of claim 3, wherein X9 represents a bond, X11 represents a bond, or X9 and X11 represent bonds.
19. The peptide of claim 9, wherein X9 represents a bond, X11 represents a bond, or X9 and X11 represent bonds.
20. The peptide of claim 3, wherein R2 represents \u2014NH2.
21. The peptide of claim 19, wherein R2 represents \u2014NH2.
22. The peptide of claim 3, wherein X6\u2014X7\u2014X8\u2014X9\u2014X10 represents D-Phe-Arg-Trp-Lys.
23. The peptide of claim 3, wherein the peptide is selected from:
R4-Nle-cAsp-3-PyAla-D-Phe-Arg-Trp-Lys-R2;
R4-Nle-cGlu-Hyp-D-Phe-Arg-Trp-Lys-R2;
R4-Nle-cAsp-Hyp-D-Phe-Arg-Trp-Lys-R2;
R4-Nle-cGlu-Gln-D-Phe-Arg-Trp-Lys-R2;
R4-Nle-cAsp-Gln-D-Phe-Arg-Trp-Lys-R2;
R4-Nle-cGlu-Asn-D-Phe-Arg-Trp-Lys-R2;
R4-Nle-cAsp-Asn-D-Phe-Arg-Trp-Lys-R2;
R4-Nle-cGlu-3-PyAla-D-Phe-Arg-2Nal-Lys-R2;
R4-Nle-cAsp-3-PyAla-D-Phe-Arg-2Nal-Lys-R2;
R4-Nle-cGlu-Hyp-D-Phe-Arg-2Nal-Lys-R2;
R4-Nle-cAsp-Hyp-D-Phe-Arg-2Nal-Lys-R2;
R4-Nle-cGlu-Gln-D-Phe-Arg-2Nal-Lys-R2;
R4-Nle-cAsp-Gln-D-Phe-Arg-2Nal-Lys-R2;
R4-Nle-cGlu-Asn-D-Phe-Arg-2Nal-Lys-R2;
and
R4-Nle-cAsp-Asn-D-Phe-Arg-2Nal-Lys-R2.
24. The peptide of claim 3, wherein X\u2014X1\u2014X2\u2014X3\u2014X4\u2014X5\u2014X6\u2014X7\u2014X8\u2014X9\u2014X10-R2 represents Nle-cGlu-3-PyAla-D-Phe-Arg-Trp-Lys-NH2 or Nle-cGlu-Hyp-D-Phe-Arg-Trp-Lys-NH2.
25. The peptide of claim 3, wherein X\u2014X1\u2014X2\u2014X3\u2014X4\u2014X5\u2014X6\u2014X7\u2014X8\u2014X9\u2014X10-R2 represents Nle-cGlu-His-D-Phe-Arg-Trp-Lys-NH2.
26. The peptide of claim 3, wherein X\u2014X1\u2014X2 is represented by a moiety of the formula Z1-Z2-Z3-Z4-Z5-Z6, wherein
Z1 represents Gly;
Z2 represents Ser, (D)-Ser or Thr;
Z3 represents Gln, Asn, (D)-Gln or (D)-Asn;
Z4 represents His, homoArg, Arg, Lys or Orn;
Z5 represents Ser, (D)-Ser or Thr; and
Z6 represents Nle.
27. The peptide of claim 26, wherein X3 represents Glu, and X10 represents Lys.
28. The peptide of claim 26, wherein X4, X9 and X11 represent a bond.
29. The peptide of claim 27, wherein X4, X9 and X11 represent a bond.
30. The peptide of claim 26, wherein X5 represents Ala, Nle, Met, Met(O), Met(O2), Gln, Gln(\u03b5-alkyl), Gln(\u03b5-aryl), Asn, Asn (\u03b5-alkyl), Asn(\u03b5-aryl), Ser, Thr, Cys, Pro, F-Pro, Hyp, (S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, Trp, 1-naphthylalanine, 2-naphthylalanine, 2-PyAla, 3-PyAla, 4-PyAla, 2-thienylalanine, 3-thienylalanine, 4-thiazolylalanine, 2-furylalanine, 3-furylalanine, Phe, wherein the phenyl moiety of said Phe is optionally substituted by halogen, hydroxyl, alkoxy, nitro, benzoyl, methyl, trifluoromethyl or cyano.
31. The peptide of claim 29, wherein X5 represents Ala, Nle, Met, Met(O), Met(O2), Gln, Gln(\u03b5-alkyl), Gln(\u03b5-aryl), Asn, Asn (\u03b5-alkyl), Asn(\u03b5-aryl), Ser, Thr, Cys, Pro, F-Pro, Hyp, (S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, Trp, 1-naphthylalanine, 2-naphthylalanine, 2-PyAla, 3-PyAla, 4-PyAla, 2-thienylalanine, 3-thienylalanine, 4-thiazolylalanine, 2-furylalanine, 3-furylalanine, Phe, wherein the phenyl moiety of said Phe is optionally substituted by halogen, hydroxyl, alkoxy, nitro, benzoyl, methyl, trifluoromethyl or cyano.
32. The peptide of claim 26, wherein X5 represents F-Pro, Hyp or Gln.
33. The peptide of claim 29, wherein X5 represents F-Pro, Hyp or Gln.
37. The peptide of claim 26, wherein R2 represents \u2014NH2.
38. The peptide of claim 26, wherein X6\u2014X7\u2014X8\u2014X9\u2014X10 represents (D)-Phe-Arg-Trp-Lys.
39. The peptide of claim 26, wherein the moiety of the formula Z1-Z2-Z3-Z4-Z5-Z6 is selected from amongst
Gly-Ser-Asn-Asn-Thr-Nle;
Gly-Ser-Asn-homoArg-Thr-Nle;
Gly-Ser-DAsn-His-Thr-Nle;
Gly-Ser-DAsn-homoArg-Thr-Nle;
Gly-Ser-Gln-Arg-Ser-Nle;
Gly-Ser-Gln-His-Ser-Nle;
Gly-Ser-Gln-homoArg-Ser-Nle;
Gly-Ser-Gln-homoArg-Thr-Nle;
Gly-Ser-Gln-Lys-Ser-Nle;
Gly-Ser-Gln-Orn-Ser-Nle;
Gly-Ser-Ser-His-Thr-Nle
and
Gly-Ser-Ser-Tyr-Thr-Nle.
40. The peptide of claim 26, wherein X3\u2014X4\u2014X5\u2014X6\u2014X7\u2014X8\u2014X9\u2014X10\u2014X11-R2 is selected from
cycloGlu-3-PyAla-(D)-Phe-Arg-Trp-Lys-NH2;
cycloGlu-F-Pro-(D)-Phe-Arg-Trp-Lys-NH2;
cycloGlu-Gln-(D)-Phe-Arg-Trp-Lys-NH2;
cycloGlu-Hyp-(D)-Phe-Arg-Trp-Lys-NH2;
and
cycloGlu-Met(O2)-(D)-Phe-Arg-Trp-Lys-NH2.
41. The peptide of claim 2, wherein the compound of formula I is non-cyclic.
42. The peptide of claim 41, wherein X represents a bond.
43. The peptide of claim 41, wherein X represents an amino acid residue.
44. The peptide of claim 43, wherein X represents Ser.
45. The peptide of claim 42, wherein X1 represents Lys(N\u03b5\u03b2-Ala-R4).
46. The peptide of claim 43, wherein X1 represents Lys(N\u03b5\u03b2-Ala-R4).
47. The peptide of claim 42, wherein X1 represents a bond.
48. The peptide of claim 45, wherein X2 represents Tyr-Ser-Nle.
49. The peptide of claim 47, wherein X2 represents Ser-Nle.
50. The peptide of claim 48, wherein X2 represents Ser-Tyr-Ser-Nle.
51. The peptide of claim 42, wherein X3 represents Glu.
52. The peptide of claim 50, wherein X3 represents Glu.
53. The peptide of claim 42, wherein X4 represents a bond.
54. The peptide of claim 52, wherein X4 represents a bond.
55. The peptide of claim 42, wherein the peptide is characterized by two or more of the following: X represents a bond or an amino acid residue; X1 represents Lys(N\u03b5\u03b2-Ala-R4) or a bond; X2 represents Tyr-Ser-Nle, Ser-Nle, or Ser-Tyr-Ser-Nle; X3 represents Glu; and X4 represents a bond.
56. The peptide of claim 42, wherein X5 represents Ala, Nle, Met, Met(O), Met(O2), Gln, Gln(\u03b5-alkyl), Gln(\u03b5-aryl), Asn, Asn (\u03b5-alkyl), Asn(\u03b5-aryl), Ser, Thr, Cys, F-Pro, Pro, Hyp, (S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, Trp, 1-naphthylalanine, 2-naphthylalanine, 2-PyAla, 3-PyAla, 4-PyAla, 2-thienylalanine, 3-thienylalanine, 4-thiazolylalanine, 2-furylalanine, 3-furylalanine, Phe, wherein the phenyl moiety of said Phe is optionally substituted by halogen, hydroxyl, alkoxy, nitro, benzoyl, methyl, trifluoromethyl or cyano.
57. The peptide of claim 42, wherein X5 represents His.
58. The peptide of claim 42, wherein X5 represents Gln, Hyp, 3-PyAla, Ala or Ser.
59. The peptide of claim 42, wherein X9 represents Gly.
60. The peptide of claim 42, wherein X10 represents Lys or Arg.
61. The peptide of claim 42, wherein X11 represents Pro-Val.
62. The peptide of claim 42, wherein the peptide is characterized by two or more of the following: X5 represents His, Gln, Hyp, 3-PyAla, Ala or Ser; X9 represents Gly; X10 represents Lys or Arg; and X11 represents Pro-Val.
63. The peptide of claim 55, wherein the peptide is characterized by two or more of the following: X5 represents His, Gln, Hyp, 3-PyAla, Ala or Ser; X9 represents Gly; X10 represents Lys or Arg; and X11 represents Pro-Val.
64. The peptide of claim 42, wherein R2 represents \u2014NH2.
65. The peptide of claim 62, wherein R2 represents \u2014NH2.
66. The peptide of claim 63, wherein R2 represents \u2014NH2.
67. The peptide of claim 1, wherein R1\u2014X\u2014X1\u2014X2\u2014X3\u2014X4\u2014X5\u2014X6\u2014X7\u2014X8\u2014X9\u2014X10-R2 represents a compound selected from amongst
CH3C(O)-Lys(N\u03b5\u03b2-Ala-R4)-Tyr-Ser-Nle-Glu-Hyp-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2
CH3C(O)-Lys(N\u03b5\u03b2-Ala-R4)-Tyr-Ser-Nle-Glu-3-PyAla-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2,
CH3C(O)-Lys(N\u03b5\u03b2-Ala-R4)-Tyr-Ser-Nle-Glu-Ser-D-Phe-Arg-Trp-Gly-Arg-Pro-Val-NH2,
CH3C(O)-Lys(N\u03b5\u03b2-Ala-R4)-Tyr-Ser-Nle-Glu-Ala-D-Phe-Arg-Trp-Gly-Arg-Pro-Val-NH2,
CH3C(O)-Lys(N\u03b5\u03b2-Ala-R4)-Tyr-Ser-Nle-Glu-Gln-D-Phe-Arg-Trp-Gly-Arg-Pro-Val-NH2,
CH3C(O)-Lys(N\u03b5\u03b2-Ala-R4)-Tyr-Ser-Nle-Glu-Hyp-D-Phe-Arg-Trp-Gly-Arg-Pro-Val-NH2
68. The peptide of claim 1, wherein R1\u2014X\u2014X1\u2014X2\u2014X3\u2014X4\u2014X5\u2014X6\u2014X7\u2014X8\u2014X9\u2014X10\u2014X11-R2 represents a compound selected from amongst
CH3C(O)-Ser-Lys(N\u03b5\u03b2-Ala-R4)-Ser-Nle-Glu-Hyp-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2,
CH3C(O)-Ser-Lys(N\u03b5\u03b2-Ala-R4)-Ser-Nle-Glu-3-PyAla-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2,
CH3C(O)-Ser-Lys(N\u03b5\u03b2-Ala-R4)-Ser-Nle-Glu-Ser-D-Phe-Arg-Trp-Gly-Arg-Pro-Val-NH2,
CH3C(O)-Ser-Lys(N\u03b5\u03b2-Ala-R4)-Ser-Nle-Glu-Ala-D-Phe-Arg-Trp-Gly-Arg-Pro-Val-NH2,
CH3C(O)-Ser-Lys(N\u03b5\u03b2-Ala-R4)-Ser-Nle-Glu-Gln-D-Phe-Arg-Trp-Gly-Arg-Pro-Val-NH2,
CH3C(O)-Ser-Lys(N\u03b5\u03b2-Ala-R4)-Ser-Nle-Glu-Hyp-D-Phe-Arg-Trp-Gly-Arg-Pro-Val-NH2,
CH3C(O)-Ser-Lys(N\u03b5\u03b2-Ala-R4)-Ser-Nle-Glu-3-PyAla-D-Phe-Arg-Trp-Gly-Arg-Pro-Val-NH2.
69. The peptide of claim 2, wherein R1\u2014X\u2014X1\u2014X2\u2014X3\u2014X4\u2014X5\u2014X6\u2014X7\u2014X8\u2014X9\u2014X10\u2014X11-R2 represents a compound selected from amongst
R4-Ser-Tyr-Ser-Nle-Glu-Gln-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2,
R4-Ser-Tyr-Ser-Nle-Glu-Hyp-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2,
R4-Ser-Tyr-Ser-Nle-Glu-3-PyAla-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2,
R4-Ser-Tyr-Ser-Nle-Glu-Ser-D-Phe-Arg-Trp-Gly-Arg-Pro-Val-NH2,
R4-Ser-Tyr-Ser-Nle-Glu-Ala-D-Phe-Arg-Trp-Gly-Arg-Pro-Val-NH2,
R4-Ser-Tyr-Ser-Nle-Glu-Gln-D-Phe-Arg-Trp-Gly-Arg-Pro-Val-NH2,
R4-Ser-Tyr-Ser-Nle-Glu-Hyp-D-Phe-Arg-Trp-Gly-Arg-Pro-Val-NH2,
R4-Ser-Tyr-Ser-Nle-Glu-3-PyAla-D-Phe-Arg-Trp-Gly-Arg-Pro-Val-NH2.
70. The peptide of claim 1, wherein R4 represents a straight, branched andor cyclic C8-20alkanoyl, C8-20alkenoyl or C8-20alkynoyl, all of which may optionally be substituted with one or more substituents selected from hydroxyl, halogen, carboxyl and aryl, wherein said aryl may optionally be further substiututed by one or more substituents selected from hydroxyl, halogen, and carboxyl.
71. The peptide of claim 70, wherein R4 represents a straight, branched andor cyclic C14-16alkanoyl, C14-16alkenoyl or C14-16alkynoyl, all of which may optionally be substituted with one or more substituents selected from hydroxyl, halogen, carboxyl and aryl, wherein said aryl may optionally be further substiututed by one or more substituents selected from hydroxyl, halogen, and carboxyl.
72. The peptide of claim 71, wherein R4 represents a straight C10-20alkanoyl, C14-16alkanoyl or C8-17alkanoyl.
73. The peptide of claim 1, wherein R4 represents octanoyl, decanoyl, dodecnoyl, tetradecanoyl, hexadecanoyl, octadecanoyl, 9-carboxy-nonanoyl, 11-carboxy-undecanoyl, 13-carboxy-tridecanoyl, 15-carboxy-pentadecanoyl, 17-carboxy-heptadecanoyl, adamantan-1-yl-acetyl, 4-(hexadecanoyl sulfamoyl)butanoyl, choloyl, lithocholyl or mPEG2000.
74. The peptide of claim 1, wherein the peptide is selected from amongst
Octanoyl-Nle-cGlu-His-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 56)
Decanoyl-Nle-cGlu-His-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 57)
Tetradecanoyl-Nle-cGlu-His-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 58)
(Adamantan-1-yl)acetyl-Nle-cGlu-His-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 59)
Tetradecanoyl-Nle-cGlu-3-PyAla-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 60)
Decanoyl-Nle-cGlu-3-PyAla-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 61)
(Adamantan-1yl)acetyl-Nle-cGlu-3-PyAla-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 62)
Acetyl-Ser-Lys(3-(dodecanoylamino)propionyl)-Ser-Nle-Glu-Ser-D-Phe-Arg-Trp-Gly-Lys-
(SEQ ID NO: 63)
Pro-Val-NH2,
Acetyl-Lys(3-(dodecanoylamino)propionyl)-Tyr-Ser-Nle-Glu-Ser-D-Phe-Arg-Trp-Gly-Lys-
(SEQ ID NO: 64)
Pro-Val-NH2,
Hexadecanoyl-Ser-Tyr-Ser-Nle-Glu-Ser-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2,
(SEQ ID NO: 65)
Hexadecanoyl-Ser-Tyr-Ser-Nle-Glu-3-PyAla-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2,
(SEQ ID NO: 66)
2-2-(Hexadecanoylamino)ethoxyethoxyacetyl-Ser-Tyr-Ser-Nle-Glu-3-PyAla-D-Phe-Arg-Trp-
(SEQ ID NO: 67)
Gly-Lys-Pro-Val-NH2,
Hexadecanoyl-\u03b2Ala-Tyr-Ser-Nle-cGlu-Hyp-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 68)
Hexadecanoyl-\u03b2Ala-Ala-Tyr-Ser-Nle-cGlu-Hyp-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 69)
Acetyl-Ser-Lys(3-(dodecanoylamino)propionyl)-Ser-Nle-Glu-Hyp-D-Phe-Arg-Trp-Gly-Lys-
(SEQ ID NO: 70)
Pro-Val-NH2,
mPEG(2000)acetyl-Nle-cGlu-Hyp-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 71)
2-2-(Lithocholoylamino)ethoxyethoxyacetyl-\u03b2Ala-Tyr-Ser-Nle-cGlu-Hyp-D-Phe-Arg-Trp-
(SEQ ID NO: 72)
Lys-NH2,
2-2-(15-Carboxypentadecanoylamino)ethoxyethoxyacetyl-\u03b2Ala-Ala-Tyr-Ser-Nle-cGlu-Hyp-
(SEQ ID NO: 73)
D-Phe-Arg-Trp-Lys-NH2,
Acetyl-Ser-Lys(3-(dodecanoylamino)propionyl)-Ser-Phe-Glu-Hyp-D-Phe-Arg-Trp-Gly-Lys-
(SEQ ID NO: 74)
Pro-Val-NH2,
2-2-(15-Carboxypentadecanoylamino)ethoxyethoxyacetyl-Ser-Gln-Ser-Nle-cGlu-Hyp-D-
(SEQ ID NO: 75)
Phe-Arg-Trp-Lys-NH2,
Hexadecanoyl-Gly-Ser-Gln-His-Ser-Nle-cGlu-Hyp-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 76)
15-Carboxypentadecanoyl-Gly-Ser-Gln-His-Ser-Nle-cGlu-Hyp-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 77)
4-(Hexadecanoylsulfamoyl)butanoyl-Gly-Ser-Gln-His-Ser-Nle-cGlu-Hyp-D-Phe-Arg-Trp-
(SEQ ID NO: 78)
Lys-NH2,
4-2-(4-\u03b2enzoylphenyl)propionylsulfamoylbutanoyl-Gly-Ser-Gln-His-Ser-Nle-cGlu-Hyp-D-
(SEQ ID NO: 79)
Phe-Arg-Trp-Lys-NH2,
2-2-(Octadecanoylamino)ethoxyethoxyacetyl-Gly-Ser-Gln-His-Ser-Nle-cGlu-Hyp-D-Phe-
(SEQ ID NO: 80)
Arg-Trp-Lys-NH2,
2-2-(Octadecanoylamino)ethoxyethoxyacetyl-Nle-cGlu-Hyp-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 81)
Hexadecanoyl-Gly-Ser-Gln-homoArg-Ser-Nle-cGlu-Hyp-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 82)
2-2-(15-Carboxypentadecanoylamino)ethoxyethoxyacetyl-Nle-cGlu-Hyp-D-Phe-Arg-Trp-
(SEQ ID NO: 83)
Lys-NH2,
Hexadecanoyl-Gly-Ser-Gln-His-Ser-Nle-cGlu-Met(O2)-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 84)
4-(Hexadecanoylsulfamoyl)butanoyl-Gly-Ser-Gln-Arg-Ser-Nle-cGlu-Met(O2)-D-Phe-Arg-Trp-
(SEQ ID NO: 85)
Lys-NH2,
Hexadecanoyl-Gly-Ser-Gln-homoArg-Ser-Nle-cGlu-3-PyAla-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 86)
Hexadecanoyl-Gly-Ser-Gln-Arg-Ser-Nle-cGlu-Met(O2)-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 87)
4-(Hexadecanoylsulfamoyl)butanoyl-Gly-Ser-Gln-Arg-Ser-Nle-cGlu-Gln-D-Phe-Arg-Trp-
(SEQ ID NO: 88)
Lys-NH2,
3-(2-{2-2-(2-(Hexadecanoylamino)ethoxy)ethoxyethoxy}ethoxy)propionyl-Nle-cGlu-Hyp-
(SEQ ID NO: 89)
D-Phe-Arg-Trp-Lys-NH2,
2-2-(Hexadecanoylamino)ethoxyethoxyacetyl-Gly-Ser-Gln-His-Ser-Nle-cGlu-Hyp-D-Phe-
(SEQ ID NO: 90)
Arg-Trp-Lys-NH2,
2-2-(Tetradecanoylamino)ethoxyethoxyacetyl-Gly-Ser-Gln-His-Ser-Nle-cGlu-Hyp-D-Phe-
(SEQ ID NO: 91)
Arg-Trp-Lys-NH2,
Hexadecanoyl-Gly-Thr-Gln-His-Ser-Nle-cGlu-Hyp-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 92)
Hexadecanoyl-Gly-Gln-Gln-His-Ser-Nle-cGlu-Hyp-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 93)
Hexadecanoyl-Gly-Thr-Gln-His-Ser-Nle-cGlu-Asn-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 94)
Hexadecanoyl-Gly-Glu-Thr-Gln-His-Ser-Nle-cGlu-Hyp-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 95)
Hexadecanoyl-Glu-Gly-Thr-Gln-His-Ser-Nle-cGlu-Hyp-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 96)
Hexadecanoyl-Glu-4-Abu-Thr-Gln-His-Ser-Nle-cGlu-Hyp-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 97)
2-2-(Hexadecanoylamino)ethoxyethoxyacetyl-His-Ser-Nle-cGlu-Hyp-D-Phe-Arg-Trp-
(SEQ ID NO: 98)
Lys-NH2,
2-2-(Hexadecanoylamino)ethoxyethoxyacetyl-Arg-Ser-Nle-cGlu-Hyp-D-Phe-Arg-Trp-
(SEQ ID NO: 99)
Lys-NH2,
2-2-(Hexadecanoylamino)ethoxyethoxyacetyl-Gln-Ser-Nle-cGlu-Hyp-D-Phe-Arg-Trp-
(SEQ ID NO: 100)
Lys-NH2,
2-2-(Hexadecanoylamino)ethoxyethoxyacetyl-Glu-Ser-Nle-cGlu-Hyp-D-Phe-Arg-Trp-
(SEQ ID NO: 101)
Lys-NH2,
2-2-(2-{2-2-(Dodecanoylamino)ethoxyethoxy}acetylamino)ethoxyethoxyacetyl-Nle-c
(SEQ ID NO: 102)
Glu-Hyp-D-Phe-Arg-Trp-Lys-NH2,
2-{2-4-Carbamoyl-2-(2-(hexadecanoylamino)acetylamino)butyrylaminoethoxy}
(SEQ ID NO: 103)
ethoxyacetyl-Nle-cGlu-Hyp-D-Phe-Arg-Trp-Lys-NH2,
2-{2-4-Carboxy-2-(2-hexadecanoylamino)acetylamino)butyrylaminoethoxy}ethoxyacetyl-
(SEQ ID NO: 104)
Nle-cGlu-Hyp-D-Phe-Arg-Trp-Lys-NH2,
2-{2-2-(2-(Hexadecanoylamino)acetylamino)-3-(imidazol-4-yl)propionylaminoethoxy}
(SEQ ID NO: 105)
ethoxyacteyl-Nle-cGlu-Hyp-D-Phe-Arg-Trp-Lys-NH2,
Dodecanoyl-Nle-cGlu-Hyp-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 106)
Hexadecanoyl-Gly-Thr-Asn-Asn-Thr-Nle-cGlu-Hyp-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 107)
Octanoyl-Gly-Ser-D-Gln-His-Thr-Nle-cGlu-Hyp-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 108)
Decanoyl-Gly-Ser-D-Gln-His-Thr-Nle-cGlu-Hyp-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 109)
Dodecanoyl-Gly-Ser-D-Gln-His-Thr-Nle-cGlu-Hyp-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 110)
Tetradecanoyl-Gly-Ser-D-Gln-His-Thr-Nle-cGlu-Hyp-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 111)
Hexadecanoyl-Gly-Ser-D-Gln-His-Thr-Nle-cGlu-Hyp-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 112)
Octadecanoyl-Gly-Ser-D-Gln-His-Thr-Nle-cGlu-Hyp-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 113)
Hexadecanoyl-Gly-Ser-Gln-His-Ser-Nle-cGlu-F-Pro-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 114)
Hexadecanoyl-Gly-Ser-Gln-homoArg-Ser-Nle-cGlu-F-Pro-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 115)
Hexadecanoyl-Gly-Ser-Gln-homoArg-Thr-Nle-cGlu-F-Pro-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 116)
Hexadecanoyl-Gly-Ser-Asn-homoArg-Thr-Ser-Nle-cGlu-F-Pro-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 117)
3-{2-2-(2-{2-4-(4,4,5,5,6,6,7,7,8,8,9,9,9-Tridecafluorononanoylsulfamoyl)
(SEQ ID NO: 118)
butyrylamino-ethoxy}ethoxy)ethoxyethoxy}propionyl-Gly-Ser-Gln-homoArg-Nle-c
Glu-Hyp-D-Phe-Arg-Trp-Lys-NH2,
Hexadecanoyl-Gly-Ser-Ser-Tyr-Thr-Nle-cGlu-Hyp-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 119)
Hexadecanoyl-Gly-Ser-Asn-Asn-Thr-Nle-cGlu-Hyp-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 120)
Hexadecanoyl-Gly-Ser-Ser-homoArg-Thr-Nle-cGlu-Hyp-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 121)
Hexadecanoyl-Gly-Ser-Ser-His-Thr-Nle-cGlu-Hyp-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 122)
Hexadecanoyl-Gly-Ser-D-Asn-His-Thr-Nle-cGlu-Hyp-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 123)
Hexadecanoyl-Gly-Ser-Asn-homoArg-Thr-Nle-cGlu-Hyp-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 124)
Hexadecanoyl-Ser-homoArg-Ser-Nle-cGlu-Met(O2)-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 125)
Hexadecanoyl-Gln-homoArg-Thr-Nle-cGlu-Met(O2)-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 126)
Hexadecanoyl-Ser-homoArg-Thr-Nle-cGlu-Met(O2)-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 127)
Hexadecanoyl-Ser-His-Thr-Nle-cGlu-Met(O2)-D-Phe-Arg-Trp-Lys-NH2,
(SEQ ID NO: 128)
and
Hexadecanoyl-Ser-homoArg-Thr-Nle-cGlu-Met(O2)-D-Phe-Arg-Trp-Lys-NH2.
(SEQ ID NO: 129)
75. A method of delaying the progression from IGT to type 2 diabetes comprising administering to a patient in need thereof an effective amount of a peptide according to claim 1, optionally in combination with at least one additional therapeutically active compound.
76. The method of claim 75, wherein the at least one additional therapeutically active compound is selected from amongst antidiabetic agents, antihyperlipidemic agents, antiobesity agents, antihypertensive agents and agents for the treatment of complications resulting from or associated with diabetes.
77. The method of claim 75, wherein the peptide is administered parenterally or sublingually.
78. A method of delaying the progression from type 2 diabetes to insulin requiring diabetes comprising administering to a patient in need thereof an effective amount of a peptide according to claim 1, optionally in combination with at least one additional therapeutically active compound.
79. The method of claim 78, wherein the at least one additional therapeutically active compound is selected from amongst antidiabetic agents, antihyperlipidemic agents, antiobesity agents, antihypertensive agents and agents for the treatment of complications resulting from or associated with diabetes.
80. The method of claim 78, wherein the peptide is administered parenterally or sublingually.
81. A method of treating obesity or preventing a subject from becoming overweight comprising administering to a patient in need thereof an effective amount of a peptide according to claim 1, optionally in combination with at least one additional therapeutically active compound.
82. The method of claim 81, wherein the at least one additional therapeutically active compound is selected from amongst antidiabetic agents, antihyperlipidemic agents, antiobesity agents, antihypertensive agents and agents for the treatment of complications resulting from or associated with diabetes.
83. The method of claim 81, wherein the peptide is administered parenterally or sublingually.
84. A method of regulating appetite comprising administering to a patient in need thereof an effective amount of a peptide according to claim 1, optionally in combination with at least one additional therapeutically active compound.
85. The method of claim 84, wherein the at least one additional therapeutically active compound is selected from amongst antidiabetic agents, antihyperlipidemic agents, antiobesity agents, antihypertensive agents and agents for the treatment of complications resulting from or associated with diabetes.
86. The method of claim 84, wherein the peptide is administered parenterally or sublingually.
87. A method of inducing satiety comprising administering to a patient in need thereof an effective amount of a peptide according to claim 1, optionally in combination with at least one additional therapeutically active compound.
88. The method of claim 87, wherein the at least one additional therapeutically active compound is selected from amongst antidiabetic agents, antihyperlipidemic agents, antiobesity agents, antihypertensive agents and agents for the treatment of complications resulting from or associated with diabetes.
89. The method of claim 87, wherein the peptide is administered parenterally or sublingually.
90. A method of preventing weight gain after successfully having lost weight comprising administering to a patient in need thereof an effective amount of a compound according to claim 1, optionally in combination with at least one additional therapeutically active compound.
91. The method of claim 90, wherein the at least one additional therapeutically active compound is selected from amongst antidiabetic agents, antihyperlipidemic agents, antiobesity agents, antihypertensive agents and agents for the treatment of complications resulting from or associated with diabetes.
92. The method of claim 90, wherein the peptide is administered parenterally or sublingually.
93. A method of increasing energy expenditure comprising administering to a patient in need thereof an effective amount of a peptide according to claim 1, optionally in combination with at least one additional therapeutically active compound.
94. The method of claim 93, wherein the at least one additional therapeutically active compound is selected from amongst antidiabetic agents, antihyperlipidemic agents, antiobesity agents, antihypertensive agents and agents for the treatment of complications resulting from or associated with diabetes.
95. The method of claim 93, wherein the peptide is administered parenterally or sublingually.
96. A method of treating a disease or state related to being overweight or obese comprising administering to a patient in need thereof an effective amount of a peptide according to claim 1, optionally in combination with at least one additional therapeutically active compound.
97. The method of claim 96, wherein the at least one additional therapeutically active compound is selected from amongst antidiabetic agents, antihyperlipidemic agents, antiobesity agents, antihypertensive agents and agents for the treatment of complications resulting from or associated with diabetes.
98. The method of claim 96, wherein the peptide is administered parenterally or sublingually.
99. A method of treating bulimia comprising administering to a patient in need thereof an effective amount of a peptide according to claim 1, optionally in combination with at least one additional therapeutically active compound.
100. The method of claim 99, wherein the at least one additional therapeutically active compound is selected from amongst antidiabetic agents, antihyperlipidemic agents, antiobesity agents, antihypertensive agents and agents for the treatment of complications resulting from or associated with diabetes.
101. The method of claim 99, wherein the peptide is administered parenterally or sublingually.
102. A method of treating a disease or condition selected from atherosclerosis, hypertension, diabetes, type 2 diabetes, impaired glucose tolerance (IGT), dyspilidemia, coronary heart disease, gallbladder disease, gall stone, osteoarthritis, cancer, sexual dysfunction, and risk of premature death, comprising administering to a patient in need thereof an effective amount of a peptide according to claim 1, optionally in combination with at least one additional therapeutically active compound.
103. The method of claim 102, wherein the at least one additional therapeutically active compound is selected from amongst antidiabetic agents, antihyperlipidemic agents, antiobesity agents, antihypertensive agents and agents for the treatment of complications resulting from or associated with diabetes.
104. The method of claim 102, wherein the peptide is administered parenterally or sublingually.
105. The method of claim 84, wherein the patient is obese or overweight.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. An apparatus, comprising:
first and second memory devices, each memory device including data storage, a controller for controlling data transfer to and from the data storage, and a plug with contacts for connecting with the power, ground, and data contacts of an independent port of a host system; and
interconnections between the first and second memory devices to share power and communicate data.
3. The apparatus of claim 1, wherein each of the ports are coupled to separate root hubs.
4. The apparatus of claim 1, wherein each port has two data contacts.
5. The apparatus of claim 4, wherein each port is a universal serial bus port.
6. The apparatus of claim 1, wherein the interconnections include one or more data communication lines between the controllers of the first and second memory devices.
7. The apparatus of claim 6, wherein the controller of the first memory device may communicate with the controller of the second memory device for access to the data storage of the second device.
8. The apparatus of claim 6, wherein the controller of the first memory device may communicate with the controller of the second device for access to the data storage of the second device, and wherein the controller of the second memory device may communicate with the controller of the first memory device for access to the data storage of the first memory device.
9. The apparatus of claim 1, wherein the interconnections are selectively coupled.
10. The apparatus of claim 9, wherein the interconnections include a pair of connectors.
11. The apparatus of claim 9, wherein the interconnections include a cable.
12. The apparatus of claim 1, wherein the first and second memory devices are physically secured together so that the plug of the first memory device is disposed in parallel with the plug of the second memory device.
13. The apparatus of claim 12, further comprising:
a housing that secures and contains the first and second memory devices.
14. The apparatus of claim 13, wherein the interconnections are contained within the housing.
15. The apparatus of claim 1, wherein each memory device further includes a communication controller for handling communication between the controller and plug of that memory device.
16. A method, comprising:
providing first and second memory devices, wherein each of the memory devices includes a plug for receiving power and communicating data with a host computer system;
sharing power between the first and second memory devices in response to at least one memory device plug being coupled to a port of the host computer system;
selectively communicating between the host computer system and the first memory device over the first memory device plug and communicating between the host computer system and the second memory device over a second memory device plug in response to each of the memory device plugs being coupled to a port of the host computer; and
selectively communicating between the host computer system and the first memory device over the first memory device plug and communicating between the host computer system and the second memory device through an interconnection with the first memory device in response to the first memory device plug being coupled to a port of the host computer system without the second memory device plug being coupled to a port of the host computer system.