compounds

Abstract

The invention provides novel compounds which are peptide hormone analogues, and which are useful in treating disorders such as diabetes and obesity. The compounds of the general sequence recited in the specification possess a tailored profile with regards to potency properties at the GIP receptor. With regard to in vivo properties, administration of example peptides of the invention have been shown, in animal models, to result in increased weight loss. Preferred compounds achieve this without reducing food intake significantly.

Description

The present inventors have found that example compounds of the invention have properties including causing weight loss in vivo. The compounds also have a long halflife in the blood, meaning that they can be administered at a conveniently low frequency. Compared with GIP and previous derivatives of GIP, the compounds of the invention have a substituent at a lysine residue at one of a number of positions in the peptide sequence, the substituted lysine is functionalised at its s-amino group, and the substituent group comprises a peptide sequence of up to 4 residues, terminating in the group R-Ri where Ri is CO2H. The inventors have additionally found that, when the amino acid residue at position Xaa12 is lysine (Lys), the resulting compounds are especially effective at achieving reduced weight gain, or achieving weight loss, in feeding studies of mice compared with corresponding compounds in which Xaa12 is not lysine. These are functionalisations that have not previously been investigated and the beneficial properties found by the current inventors have not previously been seen. As described above, the compounds of the invention have formula: Xaa1-Xaa2-Xaa3-Gly4-Thr5-Phe6-Xaa7-Ser8-Asp9-Xaa10-Ser11-Xaa12-Xaa13-Xaa14-Asp15-Lys16-Xaa17-Xaa18-Xaa19-Xaa20-Xaa21 -Phe22-Val23-Xaa24-Xaa25-Leu26-Xaa27-Xaa28-Xaa29-Xaa30-Xaa31-Xaa32-Xaa33-Xaa34-Xaa35-Xaa36-Xaa37-Xaa38-Xaa39-Xaa40-Thr41-Gln42-Xaa43 [SEQ ID NO:1] wherein: Xaa1 is DTyr, His, PheorTyr, or absent; Xaa2 is AIB or Ala, or absent; Xaa3 is Asp, Gin, Glu or His; Xaa7 is lie, Thr or Ser; Xaa10 is Tyr or His; Xaa12 is Lys; Xaa13 is AIB, Ala, Gin, Glu, Gly, His, Pro, Ser, Thr, Tyr ,Val, Asp or Asn; Xaa14 is Leu, Met or NLeu; Xaa17 is Gin or lie; Xaa18 is Ala, Arg or His; Xaa19 is Ala or Gin; Xaa20 is AIB, Gin, His, or Lys; Xaa21 is Ala, Asp or Glu; Xaa24 is Asn, Gin or Glu; Xaa25 is Arg, His, Trp or Tyr; Xaa27 is lie or Leu; Xaa28 is Ala or Asn; Xaa29 is Gin, Gly or Thr; Xaa30 is Gly, Lys or Lys*, or absent; Xaa31 is Arg, Gly or Pro, or absent; Xaa32 is Asn, Lys or Lys*, or absent; Xaa33 is Lys or Lys*, or absent; Xaa34 is Asn or Lys*, or absent; Xaa35 is Asp or absent; Xaa36 is Trp or Lys*, or absent; Xaa37 is Lys or Lys*, or absent; Xaa38 is His or absent; Xaa39 is Asn or Lys*, or absent; Xaa40 is lie, Leu or Lys*, or absent; Xaa43 is Lys* or absent; 5 wherein Lys* is Lys substituted at its s-amino group with a group of the formula: Z-Xaa44-Xaa45-Xaa46-Xaa47- wherein: Xaa44 is Gly, Ser, Thr or absent; 10 Xaa45 is Gly, Ser or absent; Xaa46 is Asn, Gin, Gly, Ser, Thr or absent; Xaa47 is Asn, Gin, Glu, Gly, His, Lys, Pro, Ser, Thr or absent; wherein R is a C8-C28 alkylene or alkenylene chain and Ri is -CO2H; and wherein the compound contains one Lys* residue. Considering the residues in turn, Xaa1 is selected from DTyr, His, Phe orTyr, orXaal is absent. Preferably, Xaa1 is selected from His, Phe and Tyr. For example, Xaa1 is selected from His and Tyr, or alternatively Xaa1 is selected from Phe and Tyr. For example, Xaa1 is Tyr. In an especially preferred embodiment, Xaa1 is Tyr. Xaa2 is selected from AIB or Ala, or absent. Preferably, Xaa2 is AIB. Xaa3 is selected from Asp, Gin, Glu or His. Preferably, Xaa3 is selected from Glu and Gin. For example, Xaa3 is Glu. Alternatively, Xaa3 is Gin. In an especially preferred embodiment, Xaa3 is Glu. Xaa7 is selected from lie, Thr or Ser. In one embodiment, Xaa7 is selected from lie or Thr. In another embodiment, Xaa7 is selected from lie or Ser. Preferably, Xaa7 is lie. Xaa10 is selected from Tyr or His. Preferably, Xaa 10 is Tyr. Xaa13 is selected from AIB, Ala, Gin, Glu, Gly, His, Pro, Ser, Thr, Tyr, Vai, Asp or Asn. In an embodiment, Xaa13 is selected from AIB, Ala, Gin, Glu, Gly, His, Pro, Ser, Thr, Tyr or Vai. Preferably, Xaa13 is selected from Ala, Gin, Thr and Vai. For example, Xaa3 is selected from Ala, Gin, and Vai. For example, Xaa13 is selected from Ala and Gin, or alternatively Xaa13 is selected from Ala and Vai. In an especially preferred embodiment, Xaa13 is Ala. In another embodiment, Xaa13 is selected from Ala, Asp, Asn, Ser. In an especially preferred embodiment, Xaa13 is Ala. Xaa14 is selected from Leu, Met or NLeu. Preferably, Xaa14 is Leu. Xaa17 is selected from Gin or lie. Preferably, Xaa17 is lie. Xaa18 is selected from Ala, Arg or His. Preferably, Xaa18 is selected from Ala and His. For example, Xaa18 is His. Alternatively, Xaa18 is Ala. In an especially preferred embodiment, Xaa18 is His. Xaa19 is selected from Ala or Gin. Preferably, Xaa19 is Gin. Xaa20 is selected from AIB, Gin, His or Lys. Preferably, Xaa20 is selected from AIB, Gin, and His. For example, Xaa20 is selected from AIB and Gin, or alternatively Xaa20 is selected from Gin and His. In an especially preferred embodiment, Xaa20 is Gin. Xaa21 is selected from Ala, Asp or Glu. Preferably, Xaa21 is selected from Asp and Glu. For example, Xaa21 is Asp. Alternatively, Xaa21 is Glu. In an especially preferred embodiment, Xaa21 is Asp. Xaa24 is selected from Asn, Gin or Glu. Preferably, Xaa24 is selected from Asn and Gin. For example, Xaa24 is Asn. Alternatively, Xaa24 is Gin. In an especially preferred embodiment, Xaa24 is Asn. Xaa25 is selected from Arg, His, Trp orTyr. Preferably, Xaa25 is Trp. Xaa27 is selected from lie or Leu. Preferably, Xaa27 is Leu. Xaa28 is selected from Ala or Asn. Preferably, Xaa28 is Ala. Xaa29 is selected from Gin, Gly or Thr. Preferably, Xaa29 is selected from Gin and Gly. For example, Xaa29 is Gin. Alternatively, Xaa29 is Gly. In an especially preferred embodiment, Xaa29 is Gin. Xaa30 is selected from Gly, Lys or Lys*, orXaa30 is absent. Preferably, Xaa30 is selected from Lys and Gly. For example, Xaa30 is Lys. Alternatively, Xaa30 is Gly. In an especially preferred embodiment, Xaa30 is Lys. Xaa31 is selected from Arg, Gly or Pro, orXaa31 is absent. Preferably, Xaa31 is selected from Gly and Pro. For example, Xaa31 is Gly. Alternatively, Xaa31 is Pro. In an especially preferred embodiment, Xaa31 is Gly. Xaa32 is selected from Asn, Lys or Lys*, orXaa32 is absent. Preferably, Xaa32 is selected from Asn, Lys and Lys*. For example, Xaa32 is selected from Lys and Lys*. Alternatively, Xaa32 is selected from Asn and Lys*. In an especially preferred embodiment, Xaa32 is Lys*. Xaa33 is Lys or Lys*; or Xaa33 is absent. Preferably, Xaa33 is selected from Lys and Lys*. Alternatively, Xaa33 is Lys or absent. In an especially preferred embodiment, Xaa33 is Lys. Xaa34 is Asn or Lys*; orXaa34 is absent. Preferably, Xaa34 is selected from Asn and Lys*, or Xaa34 is absent. For example, Xaa34 is selected from Asn and Lys*. Alternatively, Xaa34 is Asn or absent. In an especially preferred embodiment, Xaa34 is Asn. Xaa35 is Asp; orXaa35 is absent. For example, Xaa35 is Asp. Alternatively, Xaa35 is absent. In a preferred embodiment, Xaa35 is Asp. Xaa36 is Trp or Lys*; orXaa36 is absent. Preferably, Xaa36 is Trp or absent. For example, Xaa36 is Trp. Alternatively, Xaa36 is absent. In an especially preferred embodiment, Xaa35 is Trp. Xaa37 is Lys or Lys*; orXaa37 is absent. Preferably, Xaa37 is Lys or absent. For example, Xaa37 is Lys. Alternatively, Xaa37 is absent. In an especially preferred embodiment, Xaa37 is Lys. Xaa38 is His orXaa38 is absent. For example, Xaa38 is His. Alternatively, Xaa38 is absent. In an especially preferred embodiment, Xaa38 is His. Xaa39 is Asn or Lys*; orXaa39 is absent. Preferably, Xaa39 is Asn or absent. For example, Xaa39 is Asn. Alternatively, Xaa39 is absent. In an especially preferred embodiment, Xaa39 is Asn. Xaa40 is lie, Leu or Lys*; orXaa40 is absent. Preferably, Xaa40 is lie or absent. For example, Xaa40 is lie. Alternatively, Xaa40 is absent. In an especially preferred embodiment, Xaa40 is lie. Xaa41 isThr, orXaa41 is absent. Preferably, Xaa41 isThr. Xaa42 is Gin, orXaa42 is absent. Preferably, Xaa42 is Gin. Xaa43 is Lys*, or Xaa43 is absent. Preferably, Xaa43 is absent. Attachment of Lys* substituent In the compounds of the invention, the £-amino group on Lys* is attached to the a-acid group of the Xaa47 residue of the molecule, such that the bond is an amide bond. If Xaa47 is absent, then the £-amino group on Lys* is attached to the a-acid group of the next residue that is present, or the a-acid group of the Z group if no residue is present. In a lysine residue, the £-amino group is the amino group that is attached to the 6-carbon. Following standard IUPAC nomenclature, the atoms in lysine are numbered as follows, indicating the carbon atom numbering and also the a to £ positions: NH2 The £-amino group on Lys* that is referred to herein is the amino group on the C-6 carbon atom as indicated. According to the invention, the substituent may be attached to a Lys residue at any of the positions in the peptide sequence that is indicated in formula (I) by Lys*. That is to say, the substituent may be attached to a Lys residue at one of positions Xaa30, Xaa32, Xaa33, Xaa34, Xaa36, Xaa37, Xaa39, Xaa40 orXaa43. Preferred positions are selected from Xaa30, Xaa32, Xaa33, Xaa34 and Xaa43, for example Xaa32, Xaa33 and Xaa43. In an especially preferred embodiment, the substituent is attached to a Lys residue at position Xaa32. The substituent group in compounds of the invention is of the formula: Z-Xaa44-Xaa45-Xaa46-Xaa47- Considering each residue in turn: Xaa44 is selected from Gly, Ser and Thr; or Xaa44 is absent. Preferably, Xaa44 is Thr, or Xaa44 is absent. For example Xaa44 is Thr, or alternatively Xaa44 is absent. In an especially preferred embodiment, Xaa44 is absent. Xaa45 is selected from Gly and Ser; or Xaa45 is absent. For example, Xaa45 is Gly or absent. Alternatively, Xaa45 is Ser or absent. Preferably Xaa45 is Gly or absent. In an especially preferred embodiment, Xaa45 is absent. Xaa46 is selected from Asn, Gin, Gly, Ser and Thr; orXaa46 is absent. Preferably, Xaa46 is selected from Asn, Gly, Ser and Thr; orXaa46 is absent. More preferably, Xaa46 is selected from Asn, Gly and Ser; orXaa46 is absent. For example, Xaa46 is selected from Asn and Ser; orXaa46 is absent. Alternatively, Xaa46 is selected from Gly and Ser; orXaa46 is absent. In a more preferred embodiment, Xaa46 is Ser or absent. In an especially preferred embodiment, Xaa46 is absent. Xaa47 is selected from Asn, Gin, Glu, Gly, His, Lys, Pro, Ser and Thr; orXaa47 is absent. Preferably, Xaa47 is selected from Gly, Gin, His and Lys; orXaa47 is absent. More preferably, Xaa47 is selected from Gly and Lys; orXaa47 is absent. In a preferred embodiment, Xaa47 is Lys or absent. In an especially preferred embodiment, Xaa47 is Lys. Group Z The Z portion of the compounds is a group of the formula: wherein R is a C8-C28 alkylene or alkenylene chain and Ri is -CO2H. Within the Z portion of the molecule, group R is an alkylene or alkenylene chain, which is linked at one end to residue Xaa44 (or, if Xaa44 is absent, Xaa45, or if both Xaa44 and Xaa45 are absent, Xaa46, and so on; if all of Xaa44 to Xaa47 are absent, R is linked at one end to Lys*) by the Glu residue through an amide bond. At its other end, the R alkylene or alkenylene chain is linked to the Ri acid group (CO2H). Option (i) above represents the situation wherein the Glu residue in the Z group is attached to the Lys* residue through the y-carboxylic acid group of Glu. Option (ii) above represents the situation wherein the Glu residue in the Z group is attached to the Lys* residue through the a-carboxylic acid group of Glu. In a preferred embodiment of the invention, the Z portion of the compound is of formula (i), i.e. the Glu residue in the Z group is attached to the Lys* residue through the y-carboxylic acid group of Glu. Generally, R has an even number of carbon atoms. For example, R can be an alkylene or alkenylene chain that is found in naturally-occurring fatty acids. The root fatty acid has a chain length two higher than the number of carbon atoms in the R alkylene or alkenylene chain. In a preferred embodiment, R is a C16-C18 alkylene or alkenylene group. For example, R is straight chain alkylene or alkenylene group. For example, R is a C-ie or C-is straight chain alkylene group. For example, when R is a C-ie group, it can be provided by an octadecanedioic acid moiety. For example, when R is a C-is group, it can be provided by an eicosanedioic acid moiety. In a more preferred embodiment, R is a C-is alkylene group. In another embodiment of the invention, it is preferred that: Xaa1 is His, Phe orTyr; Xaa2 is AIB; Xaa3 is Glu, Gin or His; Xaa7 is lie or Ser; Xaa10 is Tyr or His; Xaa12 is Lys; Xaa13 is Ala, Asp, Asn, Gin, Ser, ThrorVal; Xaa14 is Leu or Met; Xaa17 is Gin or lie; Xaa18 is Ala or His; Xaa19 is Ala or Gin; Xaa20 is AIB, Gin, His or Lys; Xaa21 is Asp or Glu; Xaa24 is Asn, Gin or Glu; Xaa25 is Trp; Xaa27 is Leu; Xaa28 is Ala or Asn; Xaa29 is Gin, Gly or Thr; Xaa30 is Gly, Lys or Lys*; Xaa31 is Arg, Gly or Pro; Xaa32 is Asn, Lys or Lys*; Xaa33 is Lys or Lys*; or Xaa33 is absent; Xaa34 is Asn or Lys*; or Xaa34 is absent; Xaa35 is Asp; or Xaa35 is absent; Xaa36 is Trp; orXaa36 is absent; Xaa37 is Lys; orXaa37 is absent;. Xaa38 is His; orXaa38 is absent; Xaa39 is Asn; or Xaa39 is absent; Xaa40 is lie; orXaa40 is absent; Xaa41 isThr; orXaa41 is absent; Xaa42 is Gin, orXaa42 is absent; Xaa43 is Lys*; or Xaa43 is absent; wherein R is a Cie or C-ib alkylene chain and Ri is -CO2H; Xaa44 is Thr, orXaa44 is absent; Xaa45 is Gly, orXaa45 is absent; Xaa46 is Asn, Gly or Ser, orXaa46 is absent; and Xaa47 is Gly or Lys, orXaa47 is absent. For example, in such an embodiment: Xaa1 is Tyr; Xaa2 is AIB; Xaa3 is Glu; Xaa7 is lie or Ser; Xaa10 is Tyr or His; Xaa12 is Lys; Xaa13 is Asp, Asn, Ala or Ser; Xaa14 is Leu; Xaa17 is lie; Xaa18 is His; Xaa19 is Gin; Xaa20 is Gin; Xaa21 is Asp; Xaa24 is Asn; Xaa25 is Trp; Xaa27 is Leu; Xaa28 is Ala; Xaa29 is Gin; Xaa30 is Lys; Xaa31 is Gly; Xaa32 is Lys; Xaa33 is Lys* or absent; Xaa34 is Lys* or absent; Xaa35 is absent; Xaa36 is absent; Xaa37 is absent; Xaa38 is absent; Xaa39 is absent; Xaa40 is absent; Xaa41 is absent; Xaa42 is absent; Xaa43 is absent; wherein R is a C-ib alkylene chain and Ri is -CO2H; Xaa44 is absent; Xaa45 is absent; Xaa46 is Asn or absent; and Xaa47 is Lys or His, or absent. For example, Xaa47 is Lys or His. As a further example: Xaa7 is lie; Xaa10 is Tyr; Xaa12 is Lys; Xaa13 is Ala or Asp; Xaa33 is Lys*; Xaa34 is absent; Xaa46 is absent; and Xaa47 is Lys or absent. For example, Xaa47 is Lys. In an embodiment of the first aspect of the invention there is provided a compound of formula (II): W-Y (II) wherein W is an amino acid sequence: Xaa1-Xaa2-Xaa3-Gly4-Thr5-Phe6-Xaa7-Ser8-Asp9-Xaa10-Ser11-Xaa12-Xaa13-Xaa14-Asp15-Lys16-Xaa17-Xaa18-Xaa19-Xaa20-Xaa21 -Phe22-Val23-Xaa24-Xaa25-Leu26-Xaa27-Xaa28-Xaa29- [SEQ ID NO: 7] wherein: Xaa1 is DTyr, His, PheorTyr, or absent; Xaa2 is AIB or Ala, or absent; Xaa3 is Asp, Gin, Glu or His; Xaa7 is lie, Thr or Ser; Xaa10 is Tyr or His; Xaa12 is Lys; Xaa13 is AIB, Ala, Gin, Glu, Gly, His, Pro, Ser, Thr, Tyr, Vai, Asp orAsn; Xaa14 is Leu, Met or NLeu; Xaa17 is Gin or lie; Xaa18 is Ala, Arg or His; Xaa19 is Ala or Gin; Xaa20 is AIB, Gin, His or Lys; Xaa21 is Ala, Asp or Glu; Xaa24 is Asn, Gin or Glu; Xaa25 is Arg, His, Trp or Tyr; Xaa27 is lie or Leu; Xaa28 is Ala or Asn; and Xaa29 is Gin, Gly or Thr; Y is an amino acid sequence: -Xaa30-Xaa31-Xaa32-Xaa33-Xaa34 wherein: Xaa30 is Gly or Lys, or absent; Xaa31 is Arg, Gly or Pro, or absent; Xaa32 is Asn or Lys, or absent; Xaa33 is Lys, Lys* or absent; Xaa34 is Lys* or absent; wherein Lys* is Lys substituted at its s-amino group with a group of the formula: Z-Xaa44-Xaa45-Xaa46-Xaa47- wherein: Xaa44 is Gly, Ser or Thr, or absent; Xaa45 is Gly or Ser, or absent; Xaa46 is Asn, Gin, Gly, Ser or Thr, or absent; Xaa47 is Asn, Gin, Glu, Gly, His, Lys, Pro, SerorThr, or absent; and Z is a group of the formula: (i):                                           o or (ii):                            o wherein R is a C8-C28 alkylene or alkenylene chain and Ri is -CO2H; and wherein the compound of formula (I) or formula (II) contains one Lys* residue; or a derivative of the compound; or a salt or solvate of the compound or the derivative. 10 In another embodiment, when the compound of the invention is a compound of formula (II), Xaa1 is Tyr; Xaa2 is AIB; Xaa3 is Glu; 15           Xaa7 is lie, Ser or Thr; Xaa10 is Tyr or His; Xaa12 is Lys; Xaa13 is AIB, Ala, Asn, Asp, Ser or Tyr; Xaa14 is Leu; Xaa17 is Gin or lie; Xaa18 is Ala or His; Xaa19 is Ala or Gin; Xaa20 is AIB, Gin or Lys; Xaa21 is Ala, Asp or Glu; Xaa24 is Asn, Gin or Glu; Xaa25 is Arg, His, Trp or Tyr; Xaa27 is lie or Leu; Xaa28 is Ala or Asn; Xaa29 is Gin, Gly or Thr; Xaa30 is Gly or Lys, or absent; Xaa31 is Arg, Gly or Pro, or absent; Xaa32 is Asn or Lys, or absent; Xaa33 is Lys, or absent; and Xaa34 is Lys*. In a preferred embodiment, when the compound of the invention is a compound of formula (II), Xaa30 is Lys or Gly; Xaa31 is Gly or Pro; Xaa32 is Lys or absent; Xaa33 is absent; and Xaa34 is Lys*. In a preferred embodiment, when the compound of the invention is a compound of formula (II), Xaa1 is Tyr; Xaa2 is AIB; Xaa3 is Glu; Xaa7 is lie or Ser; Xaa10 is Tyr or His; Xaa12 is Lys; Xaa13 is Asp, Asn, Ala or Ser; Xaa14 is Leu; Xaa17 is lie; Xaa18 is His; Xaa19 is Gin; Xaa20 is Gin; Xaa21 is Asp; Xaa24 is Asn; Xaa25 is Trp; Xaa27 is Leu; Xaa28 is Ala; Xaa29 is Gin; Xaa30 is Lys; Xaa31 is Gly; Xaa32 is Lys; Xaa33 is Lys or absent; and Xaa34 is Lys*; wherein Lys* is Lys substituted at its s-amino group with a group of the formula: Z-Xaa44-Xaa45-Xaa46-Xaa47-; Wherein: Xaa44 is absent; Xaa45 is absent; Xaa46 is Asn or absent; and Xaa47 is Lys or His; Z is (i):                                       Q wherein R is a C-ib alkylene chain and Ri is -CO2H. For example, Xaa10 is Tyr; Xaa12 is Lys; Xaa13 is Ala or Asp; Xaa33 is absent; Xaa34 is Lys*; Xaa46 is absent; and Xaa47 is Lys. In especially preferred embodiments, the compound is one of the compounds of the invention set out in the Table of Figure 1. Derivatives and Salts The present invention provides compounds of formula (I), derivatives of such compounds, and salts or solvates of such compounds and derivatives. The compounds, derivatives and salts may be produced by recombinant methods which are well-known in the art or alternatively they may be produced by synthetic methods, again which are well-known in the art. Derivatives Whilst in some embodiments, the invention relates to a compound of formula (I) and is not a derivative, in other embodiments the invention relates to a derivative of a compound of formula (I). The derivative may for example comprise one or more derivatisations selected from amidation, glycosylation, carbamylation, acylation, sulfation, phosphorylation, cyclization, lipidization, pegylation and fusion to another peptide or protein to form a fusion protein, for example the derivative may comprise one or more derivatisations selected from amidation, glycosylation, carbamylation, acylation, sulfation, phosphorylation, cyclization, lipidization and pegylation. The structure may be modified at random positions within the molecule, or at predetermined positions within the molecule and may include one, two, three or more attached chemical moieties. In certain embodiments it is preferred that the primary peptide chain of compounds of the invention may be amidated at their C-terminal. Such a modification is very common in nature with approximately half of naturally occurring peptides, including certain gastrointestinal peptide hormones, being susceptible to amidation at their C-terminal. The present invention encompasses all of the generic and specific sequences disclosed herein, including in the sequence listing and drawings, in both amidated and non-amidated forms, the amidation, where present being especially preferred on the C-terminal of the primary peptide sequence. The derivative may for example be a fusion protein, whereby the structure of formula (I) is fused to another protein or polypeptide (the fusion partner) using recombinant methods known in the art. Alternatively, such a fusion protein may be synthetically synthesized by any known method. Such a fusion protein comprises the structure of formula (I). Any suitable peptide or protein can be used as the fusion partner (e.g., serum albumin, carbonic anhydrase, glutathione-S-transferase or thioredoxin, etc.). Such fusion proteins may be made by linking the carboxy-terminus of the fusion partner to the amino-terminus of the structure of formula (I) or vice versa. Optionally, a cleavable linker may be used to link the structure of formula (I) to the fusion partner. A resulting cleavable fusion protein may be cleaved in vivo such that an active form of a compound of the invention is released. Examples of such cleavable linkers include, but are not limited to, the linkers Asp-Asp-Asp-Asp-Tyr [SEQ ID NO: 10], Gly-Pro-Arg, Ala-Gly-Gly and His-Pro-Phe-His-Leu [SEQ ID NO: 11], which can be cleaved by enterokinase, thrombin, ubiquitin cleaving enzyme and renin, respectively. For details, see for example U.S. Patent No. 6,410,707, the contents of which are incorporated herein by reference. A derivative of the invention may for example be a physiologically functional derivative of the structure of formula (I). The term “physiologically functional derivative” is used herein to denote a chemical derivative of a compound of formula (I) having the same physiological function as the corresponding unmodified compound. For example, a physiologically functionally derivative may be convertible in the body to a compound of formula (I). According to the present invention, examples of physiologically functional derivatives include esters, amides, and carbamates; preferably esters and amides. In addition to the derivatisation at Lys*, compounds of the invention can be further derivatised at additional positions. For example, pharmaceutically acceptable esters and amides of the compounds of the invention may comprise a C1-20 alkyl-, C2-20 alkenyl-, C5-10 aryl-, C5-10 ar-Ci-20 alkyl-, or amino acid- ester group or amide group attached at an appropriate site, for example formed by reaction of an alkyl, alkenyl aryl, aralkyl or amino alkyl group containing an alcohol or amino moiety with an acid moiety present in the compound of formula (I), or formed by reaction of an alkyl, alkenyl aryl, aralkyl or amino alkyl group containing an activated acyl group with an alcohol or amine group present in the compound of formula (I). Examples of suitable moieties are hydrophobic substituents with 4 to 26 carbon atoms, preferably 5 to 19 carbon atoms. Suitable lipid groups include fatty acids (e.g. lauroyl (C12H23), palmityl (C15H31), oleyl (C15H29) or stearyl (C17H35)) and bile acids (e.g. cholate or deoxycholate). Methods for lipidization of sulfhydryl-containing compounds with fatty acid derivatives are disclosed in U.S. Patent No. 5,936,092; U.S. Patent No. 6,093,692; and U.S. Patent No. 6,225,445, the contents of which are incorporated herein by reference. Fatty acid derivatives of a compound of the invention comprising a compound of the invention linked to fatty acid via a disulfide linkage may be used for delivery of a compound of the invention to neuronal cells and tissues. Lipidisation markedly increases the absorption of the compounds relative to the rate of absorption of the corresponding unlipidised compounds, as well as prolonging blood and tissue retention of the compounds. Moreover, the disulfide linkage in a lipidised derivative is relatively labile in the cells and thus facilitates intracellular release of the molecule from the fatty acid moieties. Suitable lipid-containing moieties are hydrophobic substituents with 4 to 26 carbon atoms, preferably 5 to 19 carbon atoms. Suitable lipid groups include fatty acids (e.g. lauroyl (C12H23), palmityl (C15H31), oleyl (C15H29) or stearyl (C17H35)) and bile acids (e.g. cholate or deoxycholate). Whilst lipid functionalised compounds of the invention may have benefits in certain situations, it is expected that in most cases, it will be simplest and preferred if a compound of the invention is not further derivatised, such that there are not additional lipid groups present. Cyclization methods include cyclization through the formation of a disulfide bridge, and head-to-tail cyclization using a cyclization resin. Cyclized peptides may have enhanced stability, including increased resistance to enzymatic degradation, as a result of their conformational constraints. Cyclization may in particular be expedient where the uncyclized peptide includes an N-terminal cysteine group. Suitable cyclized peptides include monomeric and dimeric head-to-tail cyclized structures. Cyclized peptides may include one or more additional residues, especially an additional cysteine incorporated for the purpose of formation of a disulfide bond or a side chain incorporated for the purpose of resin-based cyclization. The derivative may for example be a PEGylated structure of formula (I). Derivatives which are PEGylated compounds of the invention may provide additional advantages such as increased solubility, stability and circulating time of the polypeptide, or decreased immunogenicity (see U.S. Patent No. 4,179,337, the contents of which are incorporated herein by reference). Chemical moieties for derivatisation of a compound of the invention may also be selected from water soluble polymers such as polyethylene glycol, ethylene glycol / propylene glycol copolymers, carboxymethylcellulose, dextran, polyvinyl alcohol and the like. A polymer moiety for derivatisation of a compound of the invention may be of any molecular weight and may be branched or unbranched. For ease in handling and manufacturing, the preferred molecular weight of a polyethylene glycol for derivatisation of a compound of the invention is from about 1 kDa to about 100 kDa, the term "about" indicating that in preparations of polyethylene glycol, some molecules will weigh more, some less, than the stated molecular weight. Polymers of other molecular weights may be used, depending on the desired therapeutic profile, for example the duration of sustained release desired, the effects, if any, on biological activity, the ease in handling, the degree or lack of antigenicity and other known effects of the polyethylene glycol to a therapeutic protein or analog. For example, the polyethylene glycol may have an average molecular weight of about 200, 500, 1000, 1500, 2000, 2500, 3000, 3500, 4000, 4500, 5000, 5500, 6000, 6500, 7000, 7500, 8000, 8500, 9000, 9500, 10,000, 10,500, 11,000, 11,500, 12,000, 12,500, 13,000, 13,500, 14,000, 14,500, 15,000, 15,500, 16,000, 16,500, 17,000, 17,500, 18,000, 18,500, 19,000, 19,500, 20,000, 25,000, 30,000, 35,000, 40,000, 45,000, 50,000, 55,000, 60,000, 65,000, 70,000, 75,000, 80,000, 85,000, 90,000, 95,000, or 100,000 kDa. Salts Salt forms of compounds of formula (I) and of derivatives of such compounds also form part of the invention. In some embodiments the salt is a salt of a compound of formula (I). In other embodiments the salt is a salt of a derivative of a compound of formula (I). Salts of compounds of the invention include those which are pharmaceutically acceptable, i.e. which are suitable for use in medicine. However, salts having non-pharmaceutically acceptable counterions are also within the scope of the present invention, for example, for use as intermediates in the preparation of the compounds. Suitable salts according to the invention include those formed with organic or inorganic acids or bases. Pharmaceutically acceptable acid addition salts include those formed with hydrochloric, hydrobromic, sulphuric, nitric, citric, tartaric, acetic, phosphoric, lactic, pyruvic, acetic, trifluoroacetic, succinic, perchloric, fumaric, maleic, glycolic, salicylic, oxaloacetic, methanesulfonic, ethanesulfonic, p-toluenesulfonic, formic, benzoic, malonic, naphthalene-2-sulfonic, benzenesulfonic, and isethionic acids. Other acids such as oxalic acid may be useful as intermediates in obtaining the compounds of the invention in final form. Pharmaceutically acceptable salts with bases include ammonium salts, alkali metal salts, for example potassium and sodium salts, alkaline earth metal salts, for example calcium and magnesium salts, and salts with organic bases, for example dicyclohexylamine and N-methyl-D-glucomine. Solvates Those skilled in the art of organic and / or medicinal chemistry will appreciate that many organic compounds can form complexes with solvents in which they are reacted or from which they are precipitated or crystallized. Such complexes are known as "solvates". For example, a complex with water is known as a "hydrate". The invention also encompasses solvates of the compounds of formula (I), solvates of derivatives of the compounds, and solvates of salts of the derivatives. Those skilled in the art of organic and / or medicinal chemistry will also appreciate than many organic compounds can exist in different forms, including as amorphous material and / or in one or more crystalline forms. Different physical forms of organic compounds are known as polymorphs. The invention also encompasses all such different physical forms of the compounds of formula (I), as well as different physical forms of their derivatives and salts. Biological Activity Compounds of the invention have activity at the human GIP receptor and can be considered GIP receptor agonists. This may be assessed by, for example, an in vitro or cellular binding assay or by a reporter assay. Preferred compounds of the invention exhibit an activity at the human GIP receptor that is at least 1 / 50th that of human GIP, preferably an activity which is at least 1 / 30th, 1 / 20th, 1 / 10th, 1 / 5th, 1 / 3rd or that of human GIP, for example when tested in accordance with the assay described in the examples section below. Methods of assessing activity at the GIP receptor are well known. For example, Homogeneous Time Resolved Fluorescence (R. J. Samms etal., GIPR agonism mediates weight-independent insulin sensitization by tirzepatide in obese mice, J. Clin. Invest., 2021, 131(12):e146353) detects changes in cAMP accumulation in response to Gs-coupled G protein-coupled receptor (GPCR) activation. A specific method is described herein below. Preferred compounds of the invention are effective in promoting insulin release / secretion. This may be assessed by, for example, an in vitro or in vivo assay. Methods of assessing release of insulin are well known. Compounds of the invention fulfil some, or more preferably all, of the following criteria: 1) Sustained bioactivity at the human GIP receptor resulting in inhibition of appetite; 2) Activity in promoting insulin release; 3) High solubility in aqueous solution at pH 3.0-8.0 to allow an effective dose to be administered in a low volume injection (thereby resulting in lower pain of injection). Solubility may be easily assessed by simple in vitro tests; 4) Long period of activity in vivo (as assessed in humans or an animal model) so as to permit injections no more frequently than daily and preferably no more than twice, or more preferably no more than once a week, whilst still producing acceptable therapeutic or cosmetic benefits; 5) Good weight loss (as assessed in human subjects or an animal model, where assessment may be completed with co-administration of a GLP1r agonists). According to certain embodiments of the invention, especially embodiments relating to weight loss, obesity, carbohydrate metabolism and diabetes, the compounds, derivatives and salts of the invention have one, several or all of the following features: A. Sufficient solubility between pH 3.0 and pH 8.0 to permit an effective dose to be administered in a volume of less than 1 mL, less than 0.5 mL or less than 0.3 mL; B. Activation of cAMP signalling in cells over-expressing the human GIP Receptor; C. One, several or all of the further 1 to 5 features listed above. Pharmacokinetics, Duration of Action and Solubility Compounds of the present invention exhibit potent and prolonged duration of action in vivo following subcutaneous administration. In order to achieve this, the compounds are required to have both good activity at the biological target, and excellent pharmacokinetic properties. Compounds of the present invention have a therapeutically useful duration of action and that manifests itself in the beneficial effects being observed in the experiments described herein below over several days. As well as exhibiting a long in vivo half-life, the compounds of the invention have good storage stability, with no significant degradation seen on storage in solution for 4 weeks at 4°C. Poor water solubility is a known problem for lipid containing molecules. In contrast, the compounds of the invention have very good solubility. Conditions The invention also provides a compound, derivative or salt of the invention, or a composition comprising the compound, derivative or salt together with a pharmaceutically acceptable carrier and optionally a further therapeutic agent, for use as a medicament. The invention also provides a method of treating or preventing a disease or disorder or other non-desired physiological state in a subject comprising administration of a therapeutically effective amount of a compound, derivative or salt of the invention, or of a composition comprising the compound, derivative or salt together with a pharmaceutically acceptable carrier and optionally a further therapeutic agent. Preferably the compound, derivative, salt or composition is administered subcutaneously. According to certain embodiments, the disease or disorder or other non-desired physiological state is diabetes or obesity, and particularly diabetes (e.g. type II diabetes). According to certain embodiments, the disease or disorder or other non-desired physiological state may be the physiological state of being overweight. The subject to whom the compound is administered may be overweight, for example, obese. Alternatively, or in addition, the subject may be diabetic, for example having insulin resistance or glucose intolerance, or both. The subject may have diabetes mellitus, for example, the subject may have Type II diabetes. The subject may be overweight, for example, obese and have diabetes mellitus, for example, Type II diabetes. In addition, or alternatively, the subject may have, or may be at risk of having, a disorder in which obesity or being overweight is a risk factor. Such disorders include, but are not limited to, heart disease, cardiovascular disease, for example hypertension, atherosclerosis, congestive heart failure, and dyslipidemia; stroke; gallbladder disease; osteoarthritis; sleep apnea; reproductive disorders for example, polycystic ovarian syndrome; cancers, for example breast, prostate, colon, endometrial, kidney, and esophagus cancer; varicose veins; acanthosis nigricans; eczema; exercise intolerance; insulin resistance; hypertension hypercholesterolemia; cholithiasis; osteoarthritis; orthopedic injury; insulin resistance, for example, type 2 diabetes and syndrome X; and thromboembolic disease (see Kopelman, Nature 404:635-43, 2000; Rissanen et al., British Med. J. 301, 835, 1990). Other disorders associated with obesity include depression, anxiety, panic attacks, migraine headaches, PMS, chronic pain states, fibromyalgia, insomnia, impulsivity, obsessive compulsive disorder, and myoclonus. Certain neurological disorders and certain firms of neurological degeneration are also associated with obesity. Furthermore, obesity is a recognized risk factor for increased incidence of complications of general anesthesia (see e. g., Kopelman, Nature 404:635-43, 2000). In general, obesity reduces life span and carries a serious risk of co-morbidities such as those listed above. Other diseases or disorders associated with obesity are birth defects, maternal obesity being associated with increased incidence of neural tube defects, carpal tunnel syndrome (CTS); chronic venous insufficiency (CVI); daytime sleepiness; deep vein thrombosis (DVT); end stage renal disease (ESRD); gout; heat disorders; impaired immune response; impaired respiratory function; infertility; liver disease; lower back pain; obstetric and gynecologic complications; pancreatitis; as well as abdominal hernias; acanthosis nigricans; endocrine abnormalities; chronic hypoxia and hypercapnia; dermatological effects; elephantitis; gastroesophageal reflux; heel spurs; lower extremity edema; mammegaly which causes considerable problems such as bra strap pain, skin damage, cervical pain, chronic odours and infections in the skin folds under the breasts, etc.; large anterior abdominal wall masses, for example abdominal panniculitis with frequent panniculitis, impeding walking, causing frequent infections, odours, clothing difficulties, low back pain; musculoskeletal disease; pseudotumor cerebri (or benign intracranial hypertension), and sliding hiatal hernia. In some embodiments, the disease or disorder may be non-alcoholic fatty liver disease. According to certain embodiments the disease or disorder or other non-desired physiological state may be being of a non-desired weight despite not being obese or overweight. The subject may be of normal weight (this includes but is not limited to subjects who were previously overweight or obese and who wish to prevent a return to an unhealthy weight). A subject may be a subject who desires weight loss, for example female and / or male subjects who desire a change in their appearance. In some cases where the subject is of a normal weight, aspects of the invention may relate to cosmetic treatment rather than to therapeutic treatment. The invention also provides a method of reducing appetite in a subject, reducing food intake in a subject, reducing calorie intake in a subject, improving insulin release in a subject, improving carbohydrate metabolism in a subject, and / or improving carbohydrate tolerance in a subject, comprising administration of a therapeutically effective amount of a compound, derivative, salt or composition of the invention. Such methods may relate to treating subjects having a pre-diabetic state such as insulin insensitivity or pre-diabetes. The invention also provides a method for improving a lipid profile in a subject comprising administration of a therapeutically effective amount of a compound, derivative, salt or composition of the invention. The invention also provides a method for alleviating a condition or disorder that can be alleviated by reducing nutrient availability comprising administration of a therapeutically effective amount of a compound, derivative, salt or composition of the invention. A compound, derivative, salt or composition of the invention may be used for weight control and treatment, for example reduction or prevention of obesity, in particular any one or more of the following: preventing and reducing weight gain; inducing and promoting weight loss; and reducing obesity as measured by the Body Mass Index. A compound, derivative, salt or composition of the invention may be used in maintaining any one or more of a desired body weight, a desired Body Mass Index, a desired appearance and good health. The present invention may also be used in treating, prevention, ameliorating or alleviating conditions or disorders caused by, complicated by, or aggravated by a relatively high nutrient availability. The term "condition or disorder which can be alleviated by reducing caloric (or nutrient) availability" is used herein to denote any condition or disorder in a subject that is either caused by, complicated by, or aggravated by a relatively high nutrient availability, or that can be alleviated by reducing nutrient availability, for example by decreasing food intake. Subjects who are insulin resistant, glucose intolerant, or have any form of diabetes mellitus, for example, type 1, 2 or gestational diabetes, can also benefit from methods in accordance with the present invention. Conditions or disorders associated with increased caloric intake include, but are not limited to, insulin resistance, glucose intolerance, obesity, diabetes, including type 2 diabetes, eating disorders, insulin-resistance syndromes, and Alzheimer’s disease. J. Cereb. Blood Flow Metab. 2011 Apr 13 (Teramoto S et al.) discusses the use of both GLP-1 and exendin-4 to confer cardioprotection after myocardial infarction and demonstrates that exendin-4 may be used to provide neuroprotection against cerebral ischemia-reperfusion injury. The study showed that mice receiving a transvenous injection of exendin-4, after a 60-minute focal cerebral ischemia showed significantly reduced infarct volume and improved functional deficit as well as suppressed oxidative stress, inflammatory response, and cell death after reperfusion. The study provided evidence that the protective effect of exendin-4 is mediated through increased intracellular cAMP levels and suggested that exendin-4 is potentially useful in the treatment of acute ischemic stroke. Accordingly, the invention also provides a method of providing cytoprotection in a subject, such as providing cardiac protection, providing neuroprotection and / or treating or preventing neurodegeneration, comprising administration of a therapeutically effective amount of a compound, derivative, salt or composition of the invention. In certain embodiments the disease or disorder or other non-desired physiological state which the compound, derivative, salt or composition of the invention may be used to treat or prevent is neurodegeneration. Such neurodegeneration may be caused by apoptosis, necrosis or loss of function of neuronal cells, preferably in the CNS. Neurodegeneration treated or prevented may be that following a brain injury (for example following physical trauma or following a non-traumatic injury such a stroke, tumor, hypoxia, poisoning, infection, ischemia, encephalopathy or substance abuse). Alternatively or additionally, neurodegeneration may be prevented or treated in a subject having (or diagnosed as having a predisposition to) a neurodegenerative disease such as Alzheimer’s disease, Parkinson’s disease, Gehrig’s disease (Amyotrophic Lateral Sclerosis), Huntington’s disease, Multiple Sclerosis, other demyelination related disorders, senile dementia, subcortical dementia, arteriosclerotic dementia, AIDS-associated dementia, other dementias, cerebral vasculitis, epilepsy, Tourette’s syndrome, Guillain Barre Syndrome, Wilson’s disease, Pick’s disease, neuroinflammatory disorders, encephalitis, encephalomyelitis, meningitis, other central nervous system infections, prion diseases, cerebellar ataxias, cerebellar degeneration, spinocerebellar degeneration syndromes, Friedrich’s ataxia, ataxia teangiectasia, spinal dysmyotrophy, progressive supranuclear palsy, dystonia, muscle spasticity, tremor, retinitis pigmentosa, striatonigral degeneration, mitochondrial encephalomyopathies, neuronal ceroid lipofuscinosis. Preferably, the neurodegenerative disease is selected from the group consisting of Alzheimer’s disease, Parkinson’s disease, Gehrig’s disease (Amyotrophic Lateral Sclerosis) and Huntington’s disease. In such circumstances the treatment would be regarded as neuroprotective. According to certain preferred embodiments, the treatment is neuroprotective following cerebral ischemia or neuroprotective in a subject having a neurodegenerative disease or diagnosed as having a predisposition to a neurodegenerative disease. According to other embodiments the disease or disorder or other non-desired physiological state is cardiac degeneration (in particular myocardial degeneration by apoptosis, necrosis or loss of function of myocardial cells), in which case the compound, derivative, salt or composition according to the invention provides cardiac protection. According to certain preferred embodiments that treatment is protective of myocardial function following myocardiac infarction. The invention also provides a compound, derivative, salt or composition of the invention, for use in the treatment of obesity or diabetes. The invention also provides a compound, derivative, salt or composition of the invention, for use in increasing energy expenditure of a subject, improving insulin release in a subject, improving carbohydrate tolerance in a subject and / or improving carbohydrate metabolism in a subject. Such use may relate to treating subjects having a pre-diabetic state such as insulin insensitivity or pre-diabetes. The invention also provides a compound, derivative, salt or composition of the invention, for use in the reduction of appetite in a subject, use in the reduction of food intake in a subject, use in the reduction of calorie intake in a subject, use in improving insulin release in a subject, and / or use in improving carbohydrate tolerance in a subject. Such use may relate to treating subjects having a pre-diabetic state such as insulin insensitivity or pre-diabetes. The invention also provides a compound, derivative, salt or composition of the invention, for use as a cytoprotective agent (e.g. in treating or preventing neurodegeneration, providing neuroprotection and / or providing cardiac protection). For example, the compound, derivative, salt or composition may be for use in myocardial protection in a subject following myocardial infarction, or for use in neuroprotection in a subject following cerebral ischemia or stroke, or for use in neuroprotection in a subject having a chronic neurodegenerative disease. Various features of neuroprotective or cardioprotective use of the compound, derivative, salt or composition may be as outlined above in relation to methods of the invention. In the case of neuroprotection, the subject may have experienced previously a brain injury, stroke or other event causing cerebral ischemia. Alternatively, the subject may have or have been diagnosed with a predisposition to develop a chronic neurodegenerative disease. In the case of cardioprotection the subject may have experienced previously an event causing myocardial ischemia such as a myocardial infarction and angina. According to some embodiments a compound, derivative, salt or composition of the invention may be administered as soon as possible after the subject has experienced a suspected myocardial infarction. According to certain embodiments a compound, derivative, salt or composition of the invention may be administered as soon as possible after the subject has experienced as suspected stroke. The invention also provides use of a compound, derivative, salt or composition of the invention for the manufacture of a medicament for the treatment of obesity or diabetes, of a subject, who may be as described above in reference to other aspects of the invention. The invention also provides use of a compound, derivative or salt of the invention for the manufacture of a medicament for improving insulin release in a subject, for improving carbohydrate tolerance in a subject and / or improving carbohydrate metabolism in a subject. Such use may relate to treating subjects with a pre-diabetic state such as insulin insensitivity or pre-diabetes. The invention also provides use of a compound, derivative or salt of the invention for the manufacture of a medicament for the reduction of appetite in a subject, reducing food intake in a subject, reducing calorie intake in a subject, improving insulin release in a subject, and / or use in improving carbohydrate tolerance in a subject. The invention also provides use of a compound, derivative or salt of the invention for the manufacture of a medicament for providing cytoprotection (e.g. preventing or treating neurodegeneration, providing neuroprotection and / or providing cardiac protection) of a subject, who may be as described above in reference to other aspects of the invention. According to certain embodiments the compound, derivative, salt or composition of the invention is to be administered parentally. According to other embodiments the compound, derivative, salt or composition of the invention is administered subcutaneously, intravenously, intramuscularly, intranasally, transdermally or sublingually. According to other embodiments the compound, derivative, salt or composition of the invention is administered orally. In one preferred embodiment compound, derivative, salt or composition of the invention is administered subcutaneously. The compound, derivative, salt or composition of the invention is preferably used in the treatment of a human subject. However, while the compound, derivative, salt or composition of the invention will typically be used to treat human subjects they may also be used to treat similar or identical conditions in other vertebrates for example other primates; farm animals for example swine, cattle and poultry; sport animals for example horses; or companion animals for example dogs and cats. Compositions It is preferable for the compound of formula (I), or the derivative and / or the salt thereof, to be present in a pharmaceutical formulation or composition. Accordingly, the invention provides a composition comprising a compound, derivative or salt of the invention together with a pharmaceutically acceptable excipient and optionally another therapeutic ingredient. Compositions comprising the compound, derivative or salt are suitable for pharmaceutical use. According to certain preferred embodiments the composition is present in a syringe or other administration device for subcutaneous administration to humans. According to certain preferred embodiments the composition has a pH of 3.0-8.0. Compositions of the invention may take the form of a pharmaceutical formulation as described below. The pharmaceutical formulations according to the invention include those suitable for oral, parenteral (including subcutaneous, intradermal, intramuscular, intravenous, and intra-articular), inhalation (including fine particle dusts or mists which may be generated by means of various types of metered dose pressurized aerosols, nebulizers or insufflators), rectal and topical (including dermal, transdermal, transmucosal, buccal, sublingual, and intraocular) administration, although the most suitable route may depend upon, for example, the condition and disorder of the recipient. The formulations may conveniently be presented in unit dosage form and may be prepared by any of the methods well known in the art of pharmacy. All methods include the step of bringing the active ingredient into association with the carrier which constitutes one or more accessory ingredients. In general the formulations are prepared by uniformly and intimately bringing into association the active ingredient with liquid carriers or finely divided solid carriers or both and then, if necessary, shaping the product into the desired formulation. Formulations of the present invention suitable for oral administration may be presented as discrete units such as capsules, cachets or tablets each containing a predetermined amount of the active ingredient; as a powder or granules; as a solution or a suspension in an aqueous liquid or a non-aqueous liquid; or as an oil-in-water liquid emulsion or a water-in-oil liquid emulsion. The active ingredient may also be presented as a bolus, electuary or paste. Various pharmaceutically acceptable carriers and their formulation are described in standard formulation treatises, e.g., Remington's Pharmaceutical Sciences by E. W. Martin. See also Wang, Y. J. and Hanson, M. A., Journal of Parenteral Science and Technology, Technical Report No. 10, Supp. 42:2S, 1988, the contents of which are incorporated herein by reference. A tablet may be made by compression or moulding, optionally with one or more accessory ingredients. Compressed tablets may be prepared by compressing in a suitable machine the active ingredient in a free-flowing form such as a powder or granules, optionally mixed with a binder, lubricant, inert diluent, lubricating, surface active or dispersing agent. Moulded tablets may be made by moulding in a suitable machine a mixture of the powdered compound moistened with an inert liquid diluent. The tablets may optionally be coated or scored and may be formulated so as to provide slow or controlled release of the active ingredient therein. The present compounds can, for example, be administered in a form suitable for immediate release or extended release. Immediate release or extended release can be achieved by the use of suitable pharmaceutical compositions comprising the present compounds or, particularly in the case of extended release, by the use of devices such as subcutaneous implants or osmotic pumps. The present compounds may also be administered liposomally. Preferably, compositions according to the invention are suitable for subcutaneous administration, for example by injection. According to certain embodiments the composition may contain metal ions, for example copper, iron, aluminium, zinc, nickel or cobalt ions. The presence of such ions may limit solubility and thus delay absorption into the circulatory system from the site of subcutaneous administration. Exemplary compositions for oral administration include suspensions which can contain, for example, microcrystalline cellulose for imparting bulk, alginic acid or sodium alginate as a suspending agent, methylcellulose as a viscosity enhancer, and sweeteners or flavoring agents such as those known in the art; and immediate release tablets which can contain, for example, microcrystalline cellulose, dicalcium phosphate, starch, magnesium stearate and / or lactose and / or other excipients, binders, extenders, disintegrants, diluents and lubricants such as those known in the art. Such compositions may also include a permeation enhancer. The compounds of the invention may also be delivered through the oral cavity by sublingual and / or buccal administration. Molded tablets, compressed tablets or freeze-dried tablets are exemplary forms which may be used. Exemplary compositions include those formulating the present compound(s) with fast dissolving diluents such as mannitol, lactose, sucrose and / or cyclodextrins. Also included in such formulations may be high molecular weight excipients such as celluloses (avicel) or polyethylene glycols (PEG). Such formulations can also include an excipient to aid mucosal adhesion such as hydroxypropyl cellulose (HPC), hydroxypropyl methyl cellulose (HPMC), sodium carboxy methyl cellulose (SCMC), maleic anhydride copolymer (e.g., Gantrez), and agents to control release such as polyacrylic copolymer (e.g. Carbopol 934). Lubricants, glidants, flavors, coloring agents and stabilizers may also be added for ease of fabrication and use. Formulations for parenteral administration include aqueous and non-aqueous sterile injection solutions which may contain anti-oxidants, buffers, bacteriostats and solutes which render the formulation isotonic with the blood of the intended recipient; and aqueous and non-aqueous sterile suspensions which may include suspending agents and thickening agents. The formulations may be presented in unit-dose or multi-dose containers, for example sealed ampoules and vials, and may be stored in a freeze-dried (lyophilised) condition requiring only the addition of the sterile liquid carrier, for example saline or water-for-injection, immediately prior to use. Extemporaneous injection solutions and suspensions may be prepared from sterile powders, granules and tablets of the kind previously described. Exemplary compositions for parenteral administration include injectable solutions or suspensions which can contain, for example, suitable non-toxic, parenterally acceptable diluents or solvents, such as mannitol, 1,3-butanediol, water, Ringer’s solution, an isotonic sodium chloride solution, or other suitable dispersing or wetting and suspending agents, including synthetic mono- or diglycerides, and fatty acids, including oleic acid, or Cremaphor. An aqueous carrier may be, for example, an isotonic buffer solution at a pH of from about 3.0 to about 8.0, preferably at a pH of from about 3.5 to about 7.4, for example from 3.5 to 6.0, for example from 3.5 to about 5.0. Useful buffers include sodium citrate-citric acid and sodium phosphate-phosphoric acid, and sodium acetate / acetic acid buffers. The composition preferably does not include any compounds known to be deleterious to peptide compounds. Excipients that can be included are, for instance, other proteins, such as human serum albumin or plasma preparations. If desired, the pharmaceutical composition may also contain minor amounts of non-toxic auxiliary substances, such as wetting or emulsifying agents, preservatives, and pH buffering agents and the like, for example sodium acetate or sorbitan monolaurate. Exemplary compositions for nasal aerosol or inhalation administration include solutions in saline, which can contain, for example, benzyl alcohol or other suitable preservatives, absorption promoters to enhance bioavailability, and / or other solubilizing or dispersing agents such as those known in the art. Conveniently in compositions for nasal aerosol or inhalation administration the compound of the invention is delivered in the form of an aerosol spray presentation from a pressurized pack or a nebulizer, with the use of a suitable propellant, e.g., dichlorodifluoro-methane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas. In the case of a pressurized aerosol the dosage unit can be determined by providing a valve to deliver a metered amount. Capsules and cartridges of e.g. gelatin for use in an inhaler or insufflator can be formulated to contain a powder mix of the compound and a suitable powder base, for example lactose or starch. In one specific, non-limiting example, a compound of the invention is administered as an aerosol from a metered dose valve, through an aerosol adapter also known as an actuator. Optionally, a stabilizer is also included, and / or porous particles for deep lung delivery are included (e.g., see U.S. Patent No. 6,447,743). Formulations for rectal administration may be presented as a retention enema or a suppository with the usual carriers such as cocoa butter, synthetic glyceride esters or polyethylene glycol. Such carriers are typically solid at ordinary temperatures, but liquefy and / or dissolve in the rectal cavity to release the drug. Formulations for topical administration in the mouth, for example buccally or sublingually, include lozenges comprising the active ingredient in a flavoured basis such as sucrose and acacia or tragacanth, and pastilles comprising the active ingredient in a basis such as gelatin and glycerine or sucrose and acacia. Exemplary compositions for topical administration include a topical carrier such as Plastibase (mineral oil gelled with polyethylene). Preferred unit dosage formulations are those containing an effective dose, as hereinbefore recited, or an appropriate fraction thereof, of the active ingredient. It should be understood that in addition to the ingredients particularly mentioned above, the formulations of this invention may include other agents conventional in the art having regard to the type of formulation in question, for example those suitable for oral administration may include flavouring agents. The compounds, derivatives and salts of the invention may also be suitably administered as sustained-release systems. Suitable examples of sustained-release systems of the invention include suitable polymeric materials, for example semi-permeable polymer matrices in the form of shaped articles, e.g., films, or microcapsules; suitable hydrophobic materials, for example as an emulsion in an acceptable oil; or ion exchange resins; and sparingly soluble derivatives of the compound of the invention, for example, a sparingly soluble salt. Sustained-release systems may be administered orally; rectally; parenterally; intracisternally; intravaginally; intraperitoneally; topically, for example as a powder, ointment, gel, drop or transdermal patch; bucally; or as an oral or nasal spray. Preparations for administration can be suitably formulated to give controlled release of compounds, derivatives and salts of the invention. For example, the pharmaceutical compositions may be in the form of particles comprising one or more of biodegradable polymers, polysaccharide jellifying and / or bioadhesive polymers, amphiphilic polymers, agents capable of modifying the interface properties of particles of the compounds of the invention. These compositions exhibit certain biocompatibility features which allow a controlled release of the active substance, see U.S. Patent No. 5,700,486, the contents of which are incorporated by reference. The use of a controlled release composition is preferred for indications such as the treatment of obesity and / or diabetes, where maximising the time period between injections is desirable. However, for indications such as providing neuroprotection or cardiac protection (e.g. following suspected myocardial infarction or stroke), where it is desired to achieve a therapeutic plasma concentration of the active agent in as short a time period as possible, an immediate release formulation will be preferred. In such cases, a dosage regime comprising administration of a dose of an immediate release formulation of the active agent (i.e. as soon as possible after suspected myocardial infarction or stroke) and subsequent administration of a dose of a controlled release formulation of the active agent may be preferred. A compound, derivative or salt of the invention may be delivered by way of a pump (see Langer, supra, Sefton, CRC Crit. Ref. Biomed. Eng. 14:201, 1987; Buchwald et al., Surgery 88:507, 1980; Saudeketa / ., N. Engl. J. Med. 321:574, 1989) or by a continuous subcutaneous infusion, for example, using a mini-pump. An intravenous bag solution may also be employed. The key factor in selecting an appropriate dose is the result obtained, as measured by decreases in total body weight or ratio of fat to lean mass, or by other criteria for measuring control or prevention of obesity or prevention of obesity-related conditions, as are deemed appropriate by the practitioner. Other controlled release systems are discussed in the review by Langer (Science 249:15271533, 1990) which is incorporated herein by reference. In another aspect of the disclosure compounds of the invention are delivered by way of an implanted pump, described, for example, in U.S. Patent No. 6,436,091; U.S. Patent No. 5,939,380; U.S. Patent No. 5,993,414, the contents of which are incorporated herein by reference. Implantable drug infusion devices are used to provide patients with a constant and longterm dosage or infusion of a drug or any other therapeutic agent. Essentially such device may be categorized as either active or passive. A compound, derivative or salt of the present invention may be formulated as a depot preparation. Such a long acting depot formulation can be administered by implantation, for example subcutaneously or intramuscularly; or by intramuscular injection. Thus, for example, the active ingredient can be formulated with suitable polymeric or hydrophobic materials, for example as an emulsion in an acceptable oil; or ion exchange resins; or as a sparingly soluble derivatives, for example, as a sparingly soluble salt. A therapeutically effective amount of the active agent of the invention may be administered as a single pulse dose, as a bolus dose, or as pulse doses administered overtime. Thus, in pulse doses, a bolus administration of the active agent is provided, followed by a time period wherein no active agent is administered to the subject, followed by a second bolus administration. In specific, non-limiting examples, pulse doses are administered during the course of a day, during the course of a week, or during the course of a month. Combination treatments In certain embodiments, a therapeutically effective amount of a compound, derivative, salt or composition of the invention is administered with a therapeutically effective amount of a further agent or agents. The compound, derivative or salt may for example be administered simultaneously with one or more further therapeutic agent(s), or it may be administered sequentially or separately. Accordingly, the invention provides a compound, derivative or salt of the invention for use as a medicament, wherein the compound, derivative or salt is for use with a therapeutically effective amount of a further therapeutic agent or agents (e.g. for administration simultaneously, sequentially or separately). In certain embodiments, the active agent of the invention is formulated and administered with a further therapeutic agent or agents as a single dose. In certain embodiments, the further therapeutic agent or agents is / are an additional antidiabetic, appetite suppressant, a food-intake-reducing, plasma glucose-lowering or plasma lipid-altering agent. Specific, non-limiting examples of an additional appetite suppressant include amfepramone (diethylpropion), phentermine, mazindol and phenylpropanolamine, fenfluramine, dexfenfluramine, phendimetrazine, benzphetamine, sibutramine, rimonabant, topiramate, fluoxetine, bupropion, zonisamide, naltrexone, orlistat and cetilistat. Specific, non-limiting examples of an additional anti-diabetic agent include metformin, phenformin, rosiglitazone, pioglitazone, troglitazone, repaglinide, nateglinide, tolbutamide, acetohexamide, tolazamide, chlorpropamide, glipizide, glyburide, glimepiride, gliclazide, fibroblast growth factor 21, miglitol, acarbose, exenatide, pramlintide, vildagliptin and sitagliptin. In a preferred embodiment, the further therapeutic agent or agents is / are GLP-1 receptor agonists. In another preferred embodiment, the further therapeutic agent or agents is / are amylin receptor agonists. In another preferred embodiment, the further therapeutic agent or agents is / are glucagon receptor agonists. In an alternative embodiment, the further therapeutic agents are GLP-1 receptor agonists and amylin receptor agonists. In another alternative embodiment, the further therapeutic agents are GLP-1 receptor agonists and glucagon receptor agonists. In another alternative embodiment, the further therapeutic agents are amylin receptor agonists and glucagon receptor agonists. In a further alternative embodiment, the further therapeutic agents are GLP-1 receptor agonists, amylin receptor agonists and glucagon receptor agonists. In alternative embodiments, the further therapeutic agent or agents is / are an additional cardioprotective or neuroprotective agent. Specific, non-limiting, examples of additional cardioprotective agents include aspirin, N-acetylcysteine, phenethylamines, coenzyme Q10, vitamin E, vitamin C, L-carnitine, carvedilol and dexrazoxane. Specific, nonlimiting examples of neuroprotective agents include statins such as simvastatin, steroids such as progesterone, minocycline, resveratrol and vitamin E. Examples of agents used for the treatment of Parkinson’s disease include anticholinergics, pramipexole, bromocriptine, levodopa, carbidopa, rasagiline, amantadine and ropinirole. Dosages A compound, derivative, salt or composition of the invention may be administered whenever the effect, e.g., appetite suppression, decreased food intake or decreased caloric intake, is desired, or slightly before to whenever the effect is desired, such as, but not limited to, about 10 minutes, about 15 minutes, about 30 minutes, about 60 minutes, about 90 minutes, or about 120 minutes, before the time the effect is desired. The therapeutically effective amount of the active agent of the invention will be dependent on the molecule utilized, the subject being treated, the severity and type of the affliction, and the manner and route of administration. For example, a therapeutically effective amount of a compound of the invention may vary from about 0.01 pg per kilogram (kg) body weight to about 1 g per kg body weight, for example about 0.1 pg to about 20 mg per kg body weight, for example about 1 pg to about 5 mg per kg body weight, or about 5 pg to about 1 mg per kg body weight. In one embodiment of the invention, a compound, derivative or salt of the invention may be administered to a subject at from 0.5 to 1,333 nmol per kg bodyweight, for example 1 to 1,333 nmol / kg bodyweight, for example 2 to 1,000 nmol per kg bodyweight, for example 4 to 1,333 nmol per kg bodyweight, for example from 5 to 1,000 nmol per kg bodyweight, for example at from 10 to 750 nmol per kg bodyweight, for example at from 20 to 500 nmol per kg bodyweight, in particular at from 30 to 240 nmol per kg bodyweight. In a preferred embodiment, a high activity compound of the invention is administered to a subject at from 0.2 to 10 nmol per kg bodyweight, for example 0.5 to 5.0 nmol / kg bodyweight, for example 1.0 to 2.0 nmol per kg bodyweight, for example 1.5 nmol per kg bodyweight., For a 75 kg subject, such doses correspond to dosages of from 37.5 nmol to 100 pmol, for example from 75 nmol to 100 pmol, for example from 150 nmol to 100 pmol, for example from 300 nmol to 100 pmol, for example from 375 nmol to 75 pmol, for example from 750 nmol to 56.25 pmol, for example from 1.5 to 37.5 p.mol, in particular from 2.25 to 18 pmol. In a preferred embodiment for a high activity compound of the invention, for a 75 kg subject, such doses correspond to dosages of from 15 to 750 nmol, for example 37.5 to 375.0 nmol, for example 75 to 150 5 nmol, for example 112.5 nmol. The invention also contemplates dosages ranges bounded by any of the specific dosages mentioned herein. The exact dose is readily determined by one of skill in the art based on the potency of the specific compound utilized, the route of delivery of the compound and the age, weight, sex and physiological condition of the subject. io For a compound with a long blood half-life, the doses discussed above may be given, for example, once or twice per month, or once, twice, three-times or four-times per week. For a preferred compound, a dose may be given no more frequently than once a week. Alternatively, for a compound with a shorter half-life in the blood, the doses discussed above may be given, for example, once, twice, three-times or four-times a 15 day or once or twice a week. In some embodiments, a dose may be given once every 2, 3 or 4 days. According to certain embodiments they may be administered once shortly before each meal to be taken. Examples The invention is further described with reference to the following non-limiting examples. Materials and Methods Peptide Synthesis Peptide synthesis was carried out on a tricyclic amide linker resin. Amino acids were attached using the Fmoc strategy. For the portion of the molecule from Xaa1 to Xaa34, each amino acid was added sequentially from the C- to the N-termini. Peptide couplings were mediated using reagents such as HBTU. Peptide cleavage from the resin was achieved with trifluoracetic acid in the presence of scavengers. In a second stage, the lysine residue to be substituted was functionalised at its s-amino group following deprotection of the s-amino group. The chain on the substituted lysine residue was then constructed sequentially using the same amino acid attachment chemistry. Peptides were purified by reverse phase HPLC. Quality control was performed on all purified peptides and peptides were shown in most cases to be greater than 90% pure by HPLC in two buffer systems. MALDI-MS showed the expected molecular ion. Example Synthesis Example compound 2 (GIP B) was prepared as follows using standard Fmoc chemistry: 1. Resin preparation: To the 2-CTC resin 1-chloro-2-[chloro(diphenyl)methyl]benzene (70 g) (Sub: 0.50 mmol / g) was added Fmoc-Lys(Dde)-OH (35 mmol, 1.00 eq) and DIEA (140 mmol, 4.00 eq) in DCM (500 mL). The mixture was agitated with N2 for 2 h at 20°C, then MeOH (70.0 mL) was added and agitated with N2for another 30 min. The resin was washed with DMF (800.0 mLx5). 2. Deprotection: 20% piperidine in DMF (800.0 mL) was added and the resin was agitated with N2 at 25°C for 25 min. The resin was washed with DMF (800.0 mL x 5) and the mixture was filtered to get the resin. 3. Coupling: A solution of HATU (2.85 eq) and Fmoc-Lys(Boc)-OH (3.00 eq) in DMF 5         (600.0 mL) was added to the resin, then DIEA (6.00 eq) was added and the mixture was agitated with N2 at 25°C for 30 min. The resin was washed with DMF (800.0 mLx5). 4. Steps 2 and 3 were repeated using the reagents in Table 1 for the coupling of the following amino acids (3-33): 10 Table 1: # Materials Coupling reagents 3 Fmoc-Gly-OH (3.00 eq) HATU (2.85 eq) and DIEA (6.00 eq) 4 Fmoc-Lys(Boc)-OH (3.00 eq) HATU (2.85 eq) and DIEA (6.00 eq) 5 Fmoc-Gln(Trt)-OH (3.00 eq) HATU (2.85 eq) and DIEA (6.00 eq) 6 Fmoc-Ala-OH (3.00 eq) HATU (2.85 eq) and DIEA (6.00 eq) 7 Fmoc-Leu-OH (3.00 eq) HATU (2.85 eq) and DIEA (6.00 eq) 8 Fmoc-Leu-OH (3.00 eq) HATU (2.85 eq) and DIEA (6.00 eq) 9 Fmoc-Trp(Boc)-OH (3.00 eq) HATU (2.85 eq) and DIEA (6.00 eq) 10 Fmoc-Asn(Trt)-OH (3.00 eq) HATU (2.85 eq) and DIEA (6.00 eq) 11 Fmoc-Val-OH (3.00 eq) HATU (2.85 eq) and DIEA (6.00 eq) 12 Fmoc-Phe-OH (3.00 eq) HATU (2.85 eq) and DIEA (6.00 eq) 13 Fmoc-Asp(tBu)-OH (3.00 eq) HATU (2.85 eq) and DIEA (6.00 eq) 14 Fmoc-Gln(Trt)-OH (3.00 eq) HATU (2.85 eq) and DIEA (6.00 eq) 15 Fmoc-Gln(Trt)-OH (3.00 eq) HATU (2.85 eq) and DIEA (6.00 eq) 16 Fmoc-His(Trt)-OH (3.00 eq) HATU (2.85 eq) and DIEA (6.00 eq) 17 Fmoc-lle-OH (3.00 eq) HATU (2.85 eq) and DIEA (6.00 eq) 18 Fmoc-Lys(Boc)-OH (3.00 eq) HATU (2.85 eq) and DIEA (6.00 eq) 19 Fmoc-Asp(tBu)-OH (3.00 eq) HATU (2.85 eq) and DIEA (6.00 eq) 20 Fmoc-Leu-OH (3.00 eq) HATU (2.85 eq) and DIEA (6.00 eq) 21 Fmoc-Ala-OH (3.00 eq) HATU (2.85 eq) and DIEA (6.00 eq) 22 Fmoc-Lys(Boc)-OH (3.00 eq) HATU (2.85 eq) and DIEA (6.00 eq) 23 Fmoc-Ser(tBu)-OH (3.00 eq) HATU (2.85 eq) and DIEA (6.00 eq) 24 Fmoc-Tyr(tBu)-OH (3.00 eq) HATU (2.85 eq) and DIEA (6.00 eq) 25 Fmoc-Asp(tBu)-OH (3.00 eq) HATU (2.85 eq) and DIEA (6.00 eq) 26 Fmoc-Ser(tBu)-OH (3.00 eq) HATU (2.85 eq) and DIEA (6.00 eq) 27 Fmoc-lle-OH (3.00 eq) HATU (2.85 eq) and DIEA (6.00 eq) 28 Fmoc-Phe-OH (3.00 eq) HATU (2.85 eq) and DIEA (6.00 eq) 29 Fmoc-Thr(tBu)-OH (3.00 eq) HATU (2.85 eq) and DIEA (6.00 eq) 30 Fmoc-Gly-OH (3.00 eq) HATU (2.85 eq) and DIEA (6.00 eq) 31 Fmoc-Glu(tBu)-OH (3.00 eq) HATU (2.85 eq) and DIEA (6.00 eq) 32 Fmoc-Aib-OH (3.00 eq) HATU (2.85 eq) and DIEA (6.00 eq) 33 Boc-Tyr(tBu)-OH (3.00 eq) HATU (2.85 eq) and DIEA (6.00 eq) 5.    3% N2H4-H2O / DMF (800.0 mL) was added to the resin and allowed to react for 30 min. The reaction was repeated, and the mixture was drained and washed with DMF (800.0 mL) 5 times. 5   6. Steps 2 and 3 were repeated using the reagents in Table 2 for the coupling of the remaining amino acids (34-36): Table 2: # Materials Coupling reagents 34 Fmoc-Lys(Boc)-OH (3.00 eq) HATU (2.85 eq) and DIEA (6.00 eq) 35 Fmoc-yGlu(tBu)-OH (3.00 eq) * HATU (2.85 eq) and DIEA (6.00 eq) 36 Eicosanedioic acid HATU (2.85 eq) and DIEA (6.00 eq) Group 33 in Table 1 is the residue Xaa34 in the structural definition in Figure 1 and in io the claims. Groups 34-36 are residues Xaa47 and Z in the structural definition in Figure 1 and in the claims. * As the protected glutamic acid reagent 35 has its C-1 acid group protected with tBu, it reacts at its C-5 acid with the lysine 34. It is the Fmoc-Glu-OtBu reagent that provides the glutamic acid residue portion in the Z part of the compound when Z is (i): 0 Peptide cleavage and purification: 7.    The resin was washed with MeOH (800.0 mL x 3), and dried under vacuum. Then cleavage solution (2.6 L, 91% TFA / 3% TIS / 3% H2O / 3% 3-mercaptopropionic acid) was added to the flask containing the resin at room temperature and the mixture was stirred for 2 h. 8. The peptide was precipitated with cold isopropyl ether (13.0 L), filtered and collected as a filter cake. The filter cake was washed with isopropyl ether (3 L x 2). The crude peptide was dried under vacuum for 4 h to get the crude peptide (80 g), and the identity of the crude peptide was confirmed via LCMS (LCMS of monitoring-1, Rt =1.700 min). 9. The crude peptide was purified by prep-HPLC (TFA conditions: A: 0.075% TFA in H2O, B: ACN) and prep-HPLC (HOAc conditions, A: 0.5% HOAc in H2O, B: ACN) to give the title compound (10.58 g, 2.36 mmol, 6.75% yield, 95.64% purity, HOAc) as a white solid, the identity of which was confirmed by LCMS (MH00500-2-P1-P1C, Rt = 1.115 min) and HPLC (MH00500-2-P1-P1B, Rt = 10.803 min, 95.64% purity). Equivalent methods were employed for all of the other peptides described herein. The sequences and other structural features of the exemplified peptides are shown in Figures 1 and 2. In the figure, the Lys* residue is substituted on its £ amino group with a group Z-Xaa44-Xaa45-Xaa46-Xaa47- (blank in the column in question means that the residue is absent), and Z is a group having the structure: wherein R is a C8-C28 alkylene or alkenylene group; and Ri is CO2H. The number of carbon atoms in the alkylene or alkenylene group of R (n, n = 8-28) is indicated in the column headed “n (R = Cn)” in Figure 1. In the examples shown, n is 18. In vivo efficacy study: single dose feeding studies in male mice Male mice (Charles River Ltd, Margate, UK) were used for animal experiments. Individually housed mice in IVC cages were randomised into treatment groups, with stratification by body weight. Mice were fasted overnight prior to injection. All peptide solutions were prepared freshly, immediately prior to administration. The control animals were dosed with 5% v / v water and 95% NaCI (0.9% w / v). Treatment groups received a single subcutaneous injection of 10-45 nmol / kg body weight GIP analogue in combination with 1-1.5 nmol / kg body weight GLP-1r agonist G7097, prepared in water for injection. At the time of injection (early light phase; 0900-1000), body weight was measured in grams (g) and each mouse was re-fed a known amount of food. Subsequent remaining food and body weight measurements were taken up to 72 h after dosing. Animals were given free access to water during the study period. The results for Example compounds 1 to 3 and comparative examples 1 to 3 are shown in Figures 1 and 2. Mice were fasted overnight and were dosed in the early light phase, then given a known amount of food. Mice were dosed with a single subcutaneous injection, combining a sub-therapeutic dose of a GLP-1r agonist G7097 (0.5-1 nmol / kg) and an Example compound (4.5-30 nmol / kg). In the Tables in Figures 1 and 2, column ‘n’ shows the number of times the compound in question was tested. Each test generally involved the compound being given to a group of 5 animals. The compounds were assessed for their propensity to inhibit food intake and their ability to bring about body weight change. The summation of their actions is reported as a single value, called “x”, representing potency, in Figures 1 and 2. To score “potency”, average food intake difference, measured in grams, compared to vehicle controls, was measured at at least two of the following time points: 24, 48 and 72 h post dose multiplied by the average body weight difference, measured in grams, compared to vehicle controls measured at at least two of the following time points: 24, 48 and 72 h post dose. The higher the number, the more potent the analogue. Results Figures 1 and 2 are tables providing the amino acid sequences and other structural information for the example compounds of the invention, and comparative example compounds. For example, the amino acid sequence of example compound no. 1 (GIP A) is as follows [SEQ ID NO: 10]: Tyr AIB Glu Gly Thr Phe lie Ser Asp Tyr Ser Lys Asp Leu Asp Lys lie His Gin Gin Asp Phe Vai Asn Trp Leu Leu Ala Gin Lys Gly Lys Lys* And the Lys* residue at position 34 carries on its s-amino group the group Z-Lys- where Z is a group of formula: wherein R is a C-ib straight chain alkylene group; and Ri is CO2H. The figures also summarise the results of the in vivo feeding efficacy studies with the example peptides of the invention and comparative example compounds as discussed above. As can be seen from the figures, mice which were fasted overnight and which were administered example peptides of the invention in combination with a GLP-1r agonist G7097, achieved reduced weight gain or achieved weight loss compared with mice which were administered G7097 alone or vehicle control animals. Furthermore, example 2 (GIP B) has the following structure [SEQ ID NO: 11]: Tyr AIB Glu Gly Thr Phe lie Ser Asp Tyr Ser Lys Ala Leu Asp Lys lie His Gin Gin Asp Phe Vai Asn Trp Leu Leu Ala Gin Lys Gly Lys Lys* And the Lys* residue at position 34 carries on its s-amino group the group: Z-Lys- where Z is a group of formula: 0 wherein R is a C-ib straight chain alkylene group; and Ri is CO2H. Comparative example compound 2 (Comp 2, GIP 121) has an identical structure to that of example 2 (GIP B), except for position Xaa12, which is lie; that is, Comp 2 has the following structure [SEQ ID NO: 14]: Tyr AIB Glu Gly Thr Phe lie Ser Asp Tyr Ser lie Ala Leu Asp Lys lie His Gin Gin Asp Phe Vai Asn Trp Leu Leu Ala Gin Lys Gly Lys Lys* And the Lys* residue at position 34 carries on its s-amino group the group: Z-Lys- where Z is a group of formula: wherein R is a C-ib straight chain alkylene group; and Ri is CO2H. As shown in the feeding study results in Figure 2, replacing the lie residue at position 12 in the structure with a Lys residue resulted in an improvement in the potency score X, from 8.3 to 12.0. These results show that when the amino acid residue at position 12 is lysine (Lys), the resulting compounds are especially effective at achieving reduced weight gain, or achieving weight loss. The above results support that the compounds of the invention are particularly effective at improving metabolism, and that they find use in the therapy of disorders such as obesity. Where in the foregoing description, integers or elements are mentioned which have known, obvious or foreseeable equivalents, then such equivalents are herein incorporated as if individually set forth. Reference should be made to the claims for determining the true scope of the present invention, which should be construed so as to 5 encompass any such equivalents. It will also be appreciated by the reader that integers or features of the invention that are described as preferable, advantageous, convenient or the like are optional and do not limit the scope of the independent claims. Moreover, it is to be understood that such optional integers or features, whilst of possible benefit in some embodiments of the invention, may not be desirable, and may therefore be 10 absent, in other embodiments.

Claims

1. A compound of formula:Xaa1-Xaa2-Xaa3-Gly4-Thr5-Phe6-Xaa7-Ser8-Asp9-Xaa10-Ser11-Xaa12-Xaa13-Xaa14-Asp15-Lys16-Xaa17-Xaa18-Xaa19-Xaa20-Xaa21 -Phe22-Val23-Xaa24-Xaa25-Leu26-Xaa27-Xaa28-Xaa29-Xaa30-Xaa31-Xaa32-Xaa33-Xaa34-Xaa35-Xaa36-Xaa37-Xaa38-Xaa39-Xaa40-Xaa41-Xaa42-Xaa43 [SEQ ID NO:1]wherein:Xaa1 is DTyr, His, PheorTyr, or absent;Xaa2 is AIB or Ala, or absent;Xaa3 is Asp, Gin, Glu or His;Xaa7 is lie, Thr or Ser;Xaa10 is Tyr or His;Xaa12 is Lys;Xaa13 is AIB, Ala, Gin, Glu, Gly, His, Pro, Ser, Thr, Tyr, Vai, Asp orAsn;Xaa14 is Leu, Met or NLeu;Xaa17 is Gin or lie;Xaa18 is Ala, Arg or His;Xaa19 is Ala or Gin;Xaa20 is AIB, Gin, His, or Lys;Xaa21 is Ala, Asp or Glu;Xaa24 is Asn, Gin or Glu;Xaa25 is Arg, His, Trp or Tyr;Xaa27 is lie or Leu;Xaa28 is Ala or Asn;Xaa29 is Gin, Gly or Thr;Xaa30 is Gly, Lys or Lys*, or absent;Xaa31 is Arg, Gly or Pro, or absent;Xaa32 is Asn, Lys or Lys*, or absent;Xaa33 is Lys or Lys*, or absent;Xaa34 is Asn or Lys*, or absent;Xaa35 is Asp or absent;Xaa36 is Trp or Lys*, or absent;Xaa37 is Lys or Lys*, or absent;Xaa38 is His or absent;Xaa39 is Asn or Lys*, or absent;Xaa40 is lie, Leu or Lys*, or absent;Xaa41 is Thr, or absent;Xaa42 is Gin, or absent;Xaa43 is Lys* or absent;wherein Lys* is Lys substituted at its s-amino group with a group of the formula:Z-Xaa44-Xaa45-Xaa46-Xaa47-wherein:Xaa44 is Gly, Ser, Thr or absent;Xaa45 is Gly, Ser or absent;Xaa46 is Asn, Gin, Gly, Ser, Thr or absent;Xaa47 is Asn, Gin, Glu, Gly, His, Lys, Pro, Ser, Thr or absent;and Z is a group of the formula:wherein R is a C8-C28 alkylene or alkenylene chain and Ri is -CO2H;and wherein the compound contains one Lys* residue;or a derivative of the compound; or a salt or solvate of the compound or the derivative.

2. A compound, derivative, salt or solvate as claimed in claim 1, wherein the compound is a compound of formula (II):W-Y (II)whereinW is an amino acid sequence:Xaa1-Xaa2-Xaa3-Gly4-Thr5-Phe6-Xaa7-Ser8-Asp9-Xaa10-Ser11-Xaa12-Xaa13-Xaa14-Asp15-Lys16-Xaa17-Xaa18-Xaa19-Xaa20-Xaa21 -Phe22-Val23-Xaa24-Xaa25-Leu26-Xaa27-Xaa28-Xaa29- [SEQ ID NO: 7]wherein:Xaa1 is DTyr, His, PheorTyr, or absent;Xaa2 is AIB or Ala, or absent;Xaa3 is Asp, Gin, Glu or His;Xaa7 is lie, Thr or Ser;Xaa10 is Tyr or His;Xaa12 is Lys;Xaa13 is AIB, Ala, Gin, Glu, Gly, His, Pro, Ser, Thr, Tyr, Vai, Asp orAsn;Xaa14 is Leu, Met or NLeu;Xaa17 is Gin or lie;Xaa18 is Ala, Arg or His;Xaa19 is Ala or Gin;Xaa20 is AIB, Gin, His or Lys;Xaa21 is Ala, Asp or Glu;Xaa24 is Asn, Gin or Glu;Xaa25 is Arg, His, Trp or Tyr;Xaa27 is lie or Leu;Xaa28 is Ala or Asn; andXaa29 is Gin, Gly or Thr;Y is an amino acid sequence:-Xaa30-Xaa31-Xaa32-Xaa33-Xaa34wherein:Xaa30 is Gly or Lys, or absent;Xaa31 is Arg, Gly or Pro, or absent;Xaa32 is Asn or Lys, or absent;Xaa33 is Lys, Lys* or absent; andXaa34 is Lys* or absent;5wherein Lys* is Lys substituted at its s-amino group with a group of the formula:Z-Xaa44-Xaa45-Xaa46-Xaa47-wherein:10         Xaa44 is Gly, Ser or Thr, or absent;Xaa45 is Gly or Ser, or absent;Xaa46 is Asn, Gin, Gly, Ser or Thr, or absent;Xaa47 is Asn, Gin, Glu, Gly, His, Lys, Pro, Ser or Thr, or absent;15 and Z is a group of the formula:(i):                                           ° or (ii):                            0wherein R is a C8-C28 alkylene or alkenylene chain and Ri is -CO2H;and wherein the compound of formula (I) or formula (II) contains one Lys* residue;or a derivative of the compound; or a salt or solvate of the compound or the derivative.

3. A compound, derivative, salt or solvate as claimed in claim 2 wherein:Xaa1 is His, Phe orTyr;Xaa2 is AIB;Xaa3 is Gin, Glu or His;Xaa7 is lie or Ser;Xaa10 is Tyr or His;Xaa12 is Lys;Xaa13 is Ala, Gin, Thr, Vai, Asp orAsn;Xaa14 is Leu or Met;Xaa17 is Gin or lie;Xaa18 is Ala or His;Xaa19 is Ala or Gin;Xaa20 is AIB, Gin, His or Lys;Xaa21 is Asp or Glu;Xaa24 is Asn, Gin or Glu;Xaa25 is Trp;Xaa27 is Leu;Xaa28 is Ala or Asn; andXaa29 is Gin, Gly or Thr.

4. A compound, derivative, salt or solvate as claimed in claim 3 wherein:Xaa1 is Tyr;Xaa2 is AIB;Xaa3 is Glu or Gin;Xaa7 is lie or Ser;Xaa10 is Tyr or His;Xaa12 is Lys;Xaa13 is Ala, Asp or Asn;Xaa14 is Leu;Xaa17 is lie;Xaa18 is His;Xaa19 is Gin;Xaa20 is Gin or Lys;Xaa21 is Asp;Xaa24 is Asn or Gin;Xaa25 is Trp;Xaa27 is Leu;Xaa28 is Ala; andXaa29 is Gin or Gly.

5. A compound, derivative, salt or solvate as claimed in claim 4 wherein:Xaa3 is Glu;Xaa20 is Gin;Xaa24 is Asn; andXaa29 is Gin.

6. A compound, derivative, salt or solvate as claimed in any one of claims 2 to 5, wherein the compound is a compound of formula (II).

7. A compound, derivative, salt or solvate as claimed in claim 6, wherein:Xaa30 is Lys or Gly;Xaa31 is Gly or Pro;Xaa32 is Lys or absent;Xaa33 is Lys, Lys* or absent; andXaa34 is Lys* or absent.

8. A compound, derivative, salt or solvate as claimed in claim 7, wherein:Xaa30 is Lys or Gly;Xaa31 is Gly or Pro;Xaa32 is Lys or absent;Xaa33 is absent; andXaa34 is Lys*.

9. A compound, derivative, salt or solvate as claimed in claim 7, wherein:Xaa30 is Lys;Xaa31 is Gly;Xaa32 is Lys or absent;Xaa33 is Lys, Lys* or absent; andXaa34 is Lys* or absent.

10. A compound, derivative, salt or solvate as claimed in claim 2, wherein:Xaa1 is Tyr;Xaa2 is AIB;Xaa3 is Glu;Xaa7 is lie or Ser;Xaa10 is Tyr or His;Xaa12 is Lys;Xaa13 is Asp, Asn, Ala or Ser;Xaa14 is Leu;Xaa17 is lie;Xaa18 is His;Xaa19 is Gin;Xaa20 is Gin;Xaa21 is Asp;Xaa24 is Asn;Xaa25 is Trp;Xaa27 is Leu;Xaa28 is Ala;Xaa29 is Gin;Xaa30 is Lys;Xaa31 is Gly;Xaa32 is Lys;Xaa33 is Lys or absent; andXaa34 is Lys*;wherein Lys* is Lys substituted at its s-amino group with a group of the formula:Z-Xaa44-Xaa45-Xaa46-Xaa47-Wherein:Xaa44 is absent;Xaa45 is absent;Xaa46 is Asn or absent; andXaa47 is Lys or His;wherein R is a C-ib alkylene chain and Ri is -CO2H.

11. A compound, derivative, salt or solvate as claimed in claim 10, wherein:Xaa10 is Tyr;Xaa12 is Lys;Xaa13 is Ala or Asp;Xaa33 is absent;Xaa34 is Lys*;Xaa46 is absent; andXaa47 is Lys.

12. A compound, derivative, salt or solvate as claimed in claim 1, which has an amino acid sequence corresponding to any one of the amino acid sequences listed in the Table of Figure 1.

13. A derivative of a compound as claimed in any of claims 1 to 12, or a salt or solvate of such a derivative, which comprises one or more derivatisations selected from amidation, glycosylation, carbamylation, acylation, sulfation, phosphorylation, cyclization, lipidization, pegylation and fusion to another peptide or protein to form a fusion protein.

14. A compound, derivative, salt or solvate as claimed in any of claims 1 to 13 together with a further therapeutic agent, for simultaneous, sequential or separate administration.

15. A compound, derivative, salt or solvate as claimed in claim 14, wherein the further therapeutic agent is a GLP-1 receptor agonist or an analogue of amylin.

16. A composition comprising a compound, derivative, salt or solvate as claimed in any of claims 1 to 15 together with a pharmaceutically acceptable carrier.

17. A composition as claimed in claim 16, present in a syringe or other administration device for subcutaneous administration to humans.

18. A compound, derivative, salt or solvate as claimed in any of claims 1 to 15, or a composition as claimed in claim 16 or claim 17 for use as a medicament.

19. A method of treating or preventing a disease or disorder or other non-desiredphysiological state in a subject comprising administration of a therapeutically effective amount of a compound, derivative, salt or solvate as claimed in any of claims 1 to 15, or a composition as claimed in claim 16 or claim 17.

20. A compound, derivative, salt or solvate as claimed in any of claims 1 to 15, or a composition as claimed in claim 16 or claim 17, for use in the prevention or treatment of diabetes, obesity, heart disease, stroke and non-alcoholic fatty liver disease, improving insulin release in a subject, improving carbohydrate metabolism in a subject, improving the lipid profile of a subject, reducing appetite, reducing food intake, reducing calorie intake, improving carbohydrate tolerance in a subject, and / or for use as a cytoprotective agent.

21. A compound, derivative, salt or solvate or composition for use as a cytoprotective agent as claimed in claim 20, wherein the compound, derivative, salt or composition is for use in the prevention or treatment of neurodegeneration, providing neuroprotection and / or providing cardiac protection.

22. A compound, derivative, salt or solvate or composition for use as a cytoprotective agent as claimed in claim 21, wherein the compound, derivative, salt or composition is for providing cardiac protection in a subject following a myocardial infarction.

23. A compound, derivative, salt or solvate or composition for use as a cytoprotective agent as claimed in claim 22, wherein the compound, derivative, salt or composition isfor providing neuroprotection in a subject having or diagnosed as being at risk of a chronic neurodegenerative disease.

24. A compound, derivative, salt or solvate or composition for use as claimed in claim 23, wherein the chronic neurodegenerative disease is selected from the group consisting of Alzheimer’s disease, Parkinson’s disease, Gehrig’s disease (Amyotrophic Lateral Sclerosis), Huntington’s disease, Multiple Sclerosis, other demyelination related disorders, senile dementia, subcortical dementia, arteriosclerotic dementia, AIDS-associated dementia, other dementias, cerebral vasculitis, epilepsy, Tourette’s syndrome, Guillain Barre Syndrome, Wilson’s disease, Pick’s disease, neuroinflammatory disorders, encephalitis, encephalomyelitis, meningitis, other central nervous system infections, prion diseases, cerebellar ataxias, cerebellar degeneration, spinocerebellar degeneration syndromes, Friedrich’s ataxia, ataxia teangiectasia, spinal dysmyotrophy, progressive supranuclear palsy, dystonia, muscle spasticity, tremor, retinitis pigmentosa, striatonigral degeneration, mitochondrial encephalomyopathies and neuronal ceroid lipofuscinosis.

25. A method of treating or preventing diabetes, obesity, heart disease, stroke or non-alcoholic fatty liver disease in a subject, improving insulin release in a subject, improving carbohydrate metabolism in a subject, improving the lipid profile of a subject, improving carbohydrate tolerance in a subject, reducing appetite, reducing food intake, reducing calorie intake, and / or providing cytoprotection in a subject, comprising administration of a therapeutically effective amount of a compound, derivative, salt or solvate as claimed in any one of claims 1 to 15, or a composition as claimed in claim 16 or claim 17.

26. Use of a compound, derivative, salt or solvate as claimed in any one of claims 1 to 15 for the manufacture of a medicament for the prevention or treatment of diabetes, obesity, heart disease, stroke and non-alcoholic fatty liver disease, improving insulin release in a subject, improving carbohydrate metabolism in a subject, improving the lipidprofile of a subject, improving carbohydrate tolerance in a subject, reducing appetite, reducing food intake, reducing calorie intake, and / or for use as a cytoprotective agent.

27. A method of causing weight loss or preventing weight gain in a subject for5 cosmetic purposes comprising administration of an effective amount of a compound, derivative, salt or solvate as claimed in any one of claims 1 to 15, or a composition as claimed in claim 16 or claim 17.