MELANIN-CONCENTRATING HORMONE ANALOGS

Abstract: The present invention features truncated MCH analogs active at the MCH receptor. The truncated MCH analogs are optionally modified peptide derivatives of mammalian MCH. The analogs can bind to the MCH receptor and, preferably, bring about signal transduction. MCH analogs have a variety of different uses including being used as a research tool and being used therapeutically.

Description: TITLE OF THE INVENTION MELANLN-CONCENTRATLNG HORMONE ANALOGS CROSS-REFERENCE TO RELATED APPLICATIONS The present application claims priority to provisional application U.S. Serial No. 60/179,967, filed February 3, 2000, which is hereby incorporated by reference herein. BACKGROUND OF THE INVENTION Neuropeptides present in the hypothalamus play a major role in mediating the control of body weight. (Flier, et al., 1998. Cell, 92, 437-440.) Melanin-concentrating hormone (MCH) produced in mammals is a cyclic 19-amino acid neuropeptide synthesized as part of a larger pre-prohormone precursor in the hypothalamus which also encodes neuropeptides NEI and NGE. (Nahon, et al, 1990. Mol. Endocrinol. 4, 632-637; Vaughan, et al, U.S. Patent No. 5,049,655; and Vaughan, ' et /., 1989. Endocrinology 125, 1660-1665.) MCH was first identified in salmon pituitary, and in fish MCH affects melanin aggregation thus affecting skin pigmentation. In trout and eels MCH has also been shown to be involved in stress induced or CRF-stimulated ACTH release. (Kawauchi, et al, 1983. Nature 305, 321-323.) In humans two genes encoding MCH have been identified that are expressed in the brain. (Breton, et al, 1993. Mol. Brain Res. 18, 297-310.) In mammals MCH has been localized primarily to neuronal cell bodies of the hypothalamus which are implicated in the control of food intake, including perikarya of the lateral hypothalamus and zona inertia. (Knigge, et al, 1996. Peptides 17, 1063-1073.) Pharmacological and genetic evidence suggest that the primary mode of MCH action is to promote feeding (orexigenic). MCH mRNA is up regulated in fasted mice and rats, in the ob/ob mouse and in mice with targeted disruption in the gene for neuropeptide Y (NPY). (Qu, et al, 1996. Nature 380, 243-247 and Erickson, et al, 1996. Nature 381, 415-418.) Injection of MCH centrally (ICV) stimulates food intake and MCH antagonizes the hypophagic effects seen with α melanocyte stimulating hormone (αMSH). (Qu, et al, 1996. Nature 380. 243-247.) MCH deficient mice are lean, hypophagic and have increased metabolic rate. (Shimada, et al, 1998. Nature 396, 670-673.) The administration of MCH has been indicated to useful for promoting eating, appetite or the gain or maintenance of weight. (Maratos-Fher, U.S. Patent No. 5,849,708.) MCH action is not limited to modulation of food intake as effects on the hypothalamic-pitmtary- axis have been reported. (Nahon, 1994 Critical Rev. in Neurobiol 8, 221-262.) MCH may be involved m the body response to stress as MCH can modulate the stress-induced release of CRF from the hypothalamus and ACTH from the pituitary In addition, MCH neuronal systems may be involved in reproductive or maternal function SUMMARY OF THE INVENTION The present invention features truncated MCH analogs active at the MCH receptor. The truncated MCH analogs are optionally modified peptide derivatives of mammalian MCH The analogs can bind to the MCH receptor and, preferably, bπng about signal transduction. MCH analogs have a vaπety of different uses including being used as a research tool and being used therapeutically. Thus, a first aspect of the present invention descπbes a truncated MCH analog The truncated MCH analog is an optionally modified peptide having the structure: Zl- Xl-X2-χ3-χ4-χ5-χ6-χ7 χ8-χ9-χl0.χl l.χl2.χl3.χl4.χl5-χl6.χl7.z2 wherein χl is an optionally present ammo acid that, if present, is either alanme, vahne, leucine, isoleucine, prohne, tryptophan, phenylalanme, methiomne, glycme, seπne, threonme, tyrosme, cysteme, asparagme, glutamme, lysine, arginme, histidine, aspartic acid, or glutarmc acid, or a deπvative thereof; χ2 is an optionally present amino acid that, if present, is either alanine, vahne, leucine, isoleucine, prohne, tryptophan, phenylalanme, methiomne, glycme, seπne, threonme, tyrosme, cysteme, asparagme, glutamme, lysine, arginme, histidine, aspartic acid, or glutarmc acid, or a deπvative thereof; χ3 is an optionally present ammo acid that, if present, is either alanine, vahne, leucine, isoleucine, prohne, tryptophan, phenylalanme, methiomne, glycme, seπne, threonme, tyrosme, cysteme, asparagme, glutamme, lysine, arginme, histidine, aspartic acid or glutamic acid, or a deπvative thereof; χ4 is an optionally present ammo acid that, if present, is either alan e, vahne, leucine, isoleucine, prohne, tryptophan, phenylalanme, methiomne, glycme, seπne, threonme, tyrosme, cysteme, asparagme, glutamme, lysine, arginme, histidine, aspartic acid, glutarmc acid, or norleucme, or a deπvative thereof, χ5 is an optionally present ammo acid that, if present, is either alanme, vahne, leucine, isoleucine, prohne, tryptophan, phenylalanme, methiomne, glycine, seπne, threonme, tyrosme, cysteme, asparagme, glutamme, lysine, arginme, histidine, aspartic acid or glutarmc acid, or a deπvative thereof, X6 an optionally piesent amino acid that, if present is either argmine, alanme, leucine, glycme, lysine, pioline, asparagme, seπne, histidme, mtroargmme, norleucme, or des-ammo-argmine, or a derivative thereof, ΥJ IS either c>steme, homocysteme, or pemcillamme, or a deπvative thereof, χ8 is either methiomne, norleucme, leucine, isoleucine, vahne, methionmesulfoxide, or methionmesulfone, or a deπvative thereof, χ9 \s either leucine, isoleucine, vahne, alanine, methiomne, or 5- aminopentanoic acid, or a deπvative thereof, χ!0 ϊs either glycme, alanme, leuc e, norleucme, cyclohexylalamne, 5-ammopentanoιc acid asparagme, serme, sarcosme, lsobutyπc, or gamma- ammobutyπc acid, or a deπvative thereof, Xl l is either argmine, lysine, citrullme, histidine, or mtroargmme, or a deπvative thereof, Xl2 is either vahne, leucine, isoleucine, alanine, or methiomne, or a deπvative thereof, χl3 is either phenylalanme, tyrosme, D-( -benzoylphenylalanme), tryptophan, (1')- and (2')-naphthylalanme, cyclohexylalamne, or mono and multi- substituted phenylalanme wherein each substituent is independently selected from the group consisting of O-alkyl, alkyl, OH, NO2, NH2, F, I, and Br, or a deπvative thereof, Xl4 !s either argmine, lysine, histidine, norargmme, or 5- aminopentanoic acid or a deπvative thereof, χl5 ^ either prohne, alanme, vahne, leucine, isoleucine, methiomne, sarcosme, or 5-amιnopentanoιc acid, or a deπvative thereof, Xl6 is either cysteme, homocysteine. or pemcillamme, or a deπvative thereof; Xl7 is an optionally present ammo acid that, if present, is either alanine, vahne. leucine, isoleucine, prohne, tryptophan, phenylalanme, methiomne, glycme, seπne, threonme, tyrosme, cysteme, asparagme, glutamme, lysine, arginme, histidme, aspartic acid or glutarmc acid, or a deπvative thereof; Zl is an optionally present protecting group that, if present, is covalently joined to the N-terminal ammo group; Z2 is an optionally present protecting group that, if present, is covalently joined to the C-terminal carboxy group, or a labeled deπvative of said peptide; or a pharmaceutically acceptable salt of said peptide or of said labeled deπvative. Unless otherwise stated, those ammo acids with a chiral center are provided in the L-enantiomer. Reference to "a deπvative thereof refers to the coπesponding D-amino acid, N-alkyl-amino acid and β-amino acid. Another aspect of the present invention descπbes a method of screening for a compound able to bind a MCH receptor. The method compπses the step of measuπng the ability of the compound to effect binding of a truncated MCH analog to either the MCH receptor, a fragment of the receptor compπsing a MCH binding site, a polypeptide compπsing such a fragment, or a deπvative of the polypeptide. Another aspect of the present invention descπbes a method for increasing weight in a subject. The method compπses the step of administeπng to the subject an effective amount of a truncated MCH analog to produce a weight increase Another aspect of the present invention descπbes a method for increasing appetite in a subject. The method compπses the step of administeπng to the subject an effective amount of a truncated MCH analog to produce an appetite increase. Another aspect of the present invention descπbes a method for measuπng the ability of a compound to decrease weight or appetite in a subject. The method compπsing the steps of a) administeπng to the subject an effective amount of a truncated MCH analog to produce a weight increase or appetite increase, b) administering the compound to the subject, and c) measuring the change in weight or appetite of the subject. Other features and advantages of the present invention are apparent from the additional descriptions provided herein including the different examples. The provided examples illustrate different components and methodology useful in practicing the present invention. The examples do not limit the claimed invention. Based on the present disclosure the skilled artisan can identify and employ other components and methodology useful for practicing the present invention. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 illustrates the results of an alanine scan where different amino acid residues of human MCH were replaced with alanine. The binding assay was performed by measuring inhibition of (125i-tyrosine, phenylalaninel3)-MCH binding to cloned human MCH receptor (CHO clone). Cyclization sites (S-S) are indicated by "*". DETAILED DESCRIPTION OF THE INVENTION Truncated MCH analogs contain about 10 to about 17 groups that are amino acids or amino acid derivatives. Using the present application as a guide truncated MCH analogs can be produced having significant MCH receptor activity, and in some cases having activity equal to or better than naturally occurring mammalian MCH. The smaller size of truncated MCH analogs offers advantages over longer-length MCH such as ease of synthesis and/or increased solubility in physiological buffers. The MCH receptor is a G-protein coupled receptor that appears to be able to couple to Gi and Gq. Several references describe a receptor that is indicated to be a MCH receptor. (Chambers, et al, 1999. Nature 400, 261-265; Saito, et al, 1999. Nature 400, 265-269; Bachner, et al, 1999. FEBS Letters 457:522-524; and Shimomura, et al, 1999. Biochemical and Biophysical Research Communications 261, 622-626. These references are not admitted to be prior art to the claimed invention.) The nucleic acid encoding for different variants of a MCH receptor is provided for by SEQ. ID. NOS. 1-3. The encoded amino acid sequences of the variants are provided by SEQ. ID. NOS. 4-6. The variants differ from each other by the presence of additional ammo acids at the N-terrmnal. One or more of these vanants may be a physiological MCH receptor Significant MCH activity is preferably at least about 50%, at least about 75%, at least about 90%, or at least about 95%, the activity of mammalian MCH as determined by a binding assay or MCH receptor activity assay. Examples of such assays are provided below. MCH analogs have a vaπety of different uses including being used as a research tool and being used therapeutically. Research tool applications generally involve the use of a truncated MCH analog and the presence of a MCH receptor or fragment thereof. The MCH receptor can be present in different environments such as a mammalian subject, a whole cell, and membrane fragments. Examples of research tool applications of truncated MCH analogs include screening for compounds active at the MCH receptor, determining the presence of the MCH receptor in a sample or preparation, examining the role or effect of MCH, and examining the role or effect of MCH antagonists Truncated MCH analogs can be used to screen for both MCH agonists and MCH antagonists. Screening for MCH agonists can be performed, for example, by using a truncated MCH analog in a competition experiment with test compounds Screening for MCH antagonists can be performed, for example, by using a truncated MCH analog to produce MCH receptor activity and then measuπng the ability of a compound to alter MCH receptor activity. Truncated MCH analogs can be administered to a subject. A "subject" refers to a mammal including, for example, a human, a rat, a mouse, or a farm animal. Reference to subject does not necessaπly indicate the presence of a disease or disorder. The term subject includes, for example, mammals being dosed with a truncated MCH analog as part of an expeπment, mammals being treated to help alleviate a disease or disorder, and mammals being treated prophylactically to retard or prevent the onset of a disease or disorder. MCH agonists can be used to achieve a beneficial effect in a subject For example, a MCH agonist can be used to facilitate a weight gam, maintenance of weight and/or an appetite increase. Such effects are particularly useful for a patient having a disease or disorder, or under going a treatment, accompanied by weight loss. Examples of diseases or disorders accompanied by weight loss include anorexia, AIDS, wasting, cachexia, and frail elderly. Examples of treatments accompanied by weight loss include chemotherapy, radiation therapy, and dialysis. MCH antagonists can also be used to achieve a beneficial effect in a patient For example, a MCH antagonist can be used to facilitate weight loss, appetite decrease, weight maintenance, cancer (e g , colon or breast) treatment, pam reduction, stress reduction and/or treatment of sexual dysfunction Truncated MCH Analogs A truncated MCH analog is an optionally modified peptide having the structure Zl- Xl-X2-χ3.χ4.χ5.χ6-χ7 χ8.χ9.χl0.χl l.χl2.χl3.χl4.χl5-χl6.χl7-z2 wherein Xl is an optionally present ammo acid that, if present, is either alanine, vahne, leucine, isoleucine, prohne, tryptophan, phenylalanme, methiomne, glycme, seπne, threonme, tyrosme, cysteme, asparagme, glutamme, lysine, arginme, histidme, aspartic acid, or glutarmc acid, or a deπvative thereof, preferably, Xl if present is aspartic acid or glutarmc acid, more preferably, Xl if present is aspartic acid, and more preferably, χl is not present, χ is an optionally present ammo acid that, if present, is either alanine, vahne, leucine, isoleucine, prohne, tryptophan, phenylalanme, methiomne, glycme, seπne, threonme, tyrosme, cysteme, asparagme, glutamme, lysine, argmine, histidme, aspartic acid, or glutarmc acid, or a deπvative thereof, preferably, χ2 if present is phenylalanme or tyrosme, more preferably, χ if present is phenylalanme, and more preferably, χ2 is not present, χ is an optionally piesent amino acid that, if present, is either alanine, vahne, leucine, isoleucine, prohne, tryptophan, phenylalanme, methiomne, glycme, seπne, threonme, tyrosme, cysteme, asparagme, glutamme, lysine, argmine, histidme, aspartic acid or glutarmc acid, or a deπvative thereof, preferably, χ3 if present is aspartic acid or glutarmc acid, more preferably, χ if present is aspartic acid, and more preferably, χ is not present, χ4 is an optionally present amino acid that, if present, is either alanine, vahne, leucine, isoleucine, prohne, tryptophan, phenylalanme, methiomne, glycme, seπne, threonme, tyrosme, cysteme, asparagme, glutamme, lysine, arg ine, histidine, aspartic acid, glutarmc acid, or norleucme, or a deπvative thereof, preferably, χ4 if present is methiomne, leucme, isoleucine, vahne, alanme or norleucme; more preferably, χ4 if present is methiomne; and more preferably, χ is not present, χ5 is an optionally present amino acid that, if present, is either alanine, vahne, leucine, isoleucine, prohne, tryptophan, phenylalanme, methiomne, glycine, seπne, threonme, tyrosme, cysteme, asparagme, glutamme, lysine, argmine, histidme, aspartic acid or glutamic acid, or a deπvative thereof; preferably, χ5 if present is leucine, methiomne, isoleucine, vahne or alanme, more preferably, χ5 if present is leucine; and more preferably, χ5 is not present, χ6 is an optionally present amino acid that, if present is either arginme, alanme, leucine, glycine, lysine, prohne, asparagme, seπne, histidme, mtroargmme, norleucme, or des-amino-argmme, or a deπvative thereof; preferably χ6 is not present or is either arginme, D-argmme, D-norleucme, D-prolme, D-seπne, or D-asparagme; more preferably χ6 is argin e or D-arginme, χ7 is either cysteme, homocysteme, or pemcillamine, or a deπvative thereof; preferably, χ7 is cysteme, χ8 is either methiomne, norleucme, leucine, isoleucine, vahne, methioninesulfoxide, or methioninesulfone, or a deπvative thereof; preferably, χ8 is methiomne, norleucme, or N-methyl norleucme; χ9 is either leucine, isoleucine, vahne, alan e, methiomne, or 5- ammopentanoic acid, or a deπvative thereof; preferably, χ9 is leucine; χl0 is either glycme, alanine, leucine, norleucme, cyclohexylalamne, 5-ammopentanoιc acid, gamma-aminobutyπc acid, asparagme, seπne, sarcosme, or isobutyπc or a deπvative thereof, preferably, XlO is either glycine, alanine, leucine, norleucme, asparagme, seπne, D-norleucme, D-prolme, gamma-aminobutyπc acid, or sarcosme; more preferably XlO, is either glycme, leucine, norlecme, asparagme, or seπne; Xll is either argmine, lysine, citrulhne, histidme, or mtroargmme, or a deπvative thereof; preferably, Xl 1 is arginme, χ!2 is either vahne, leucine, isoleucine, alanme, or methiomne, or a deπvative thereof; preferably, Xl ΪS vahne; Xl is either phenylalanme, tyrosme, D-( -benzoylphenylalanιne), tryptophan, (1')- and (2')-naphthylalanme, cyclohexylalamne, or mono and multi- substituted phenylalanme wherein each substituent is independently selected from the group consisting of O-alkyl, alkyl, OH, NO2, NH2, F, I, and Br; or a deπvative thereof; preferably, Xl3 is phenylalanine. (2')napthylalanine, p-fluoro-phenylalanine, tyrosine, or cyclohexylalamne; Xl4 is either arginine, lysine, histidine or norarginine, or 5- aminopentanoic acid, or a derivative thereof; preferably, Xl is arginine; Xl5 is either proline, alanine, valine, leucine, isoleucine, methionine, sarcosine, or 5-aminopentanoic acid, or a derivative thereof; preferably, Xl5 is proline or sarcosine; Xl6 is either cysteine, homocysteine, or penicillamine, or a derivative thereof; preferably, Xl6 is cysteine or D-cysteine; χl7 is an optionally present amino acid that, if present, is either alanine, valine, leucine, isoleucine, proline, tryptophan, phenylalanine, methionine, glycine, serine, threonine, tyrosine, cysteine, asparagine, glutamine, lysine, arginine. histidine, aspartic acid or glutamic acid, or a derivative thereof; preferably, Xl7 if present is tyrosine or tryptophan; more preferably Xl7 is not present; Zl is an optionally present protecting group that, if present, is covalently joined to the N-terminal amino group; Z2 is an optionally present protecting group that, if present, is covalently joined to the C-terminal carboxy group; or a labeled derivative of said peptide; or a pharmaceutically acceptable salt of said peptide or of said labeled derivative. The present invention is meant to comprehend diastereomers as well as their racemic and resolved enantiomerically pure forms. Truncated MCH analogs can contain D-amino acids, L-amino acids or a combination thereof. Preferably, amino acids present in a truncated MCH analog are the L-enantiomer. In different embodiments, MCH analogs contain a preferred (or more preferred) group at one or more different locations. More preferred embodiments contain preferred (or more prefeπed) groups in each of the different locations. A protecting group covalently joined to the N-terminal amino group reduces the reactivity of the amino terminus under in vivo conditions. Amino protecting groups include optionally substituted -Cj_ι 0 alkyl, optionally substituted -C 2 -ιo alkenyl, optionally substituted aryl, -Cι_ alkyl optionally substituted aryl, -C(O)-(CH 2 ) 1-6 -COOH, -C(O)- Cι- 6 alkyl, -C(O)-optionally substituted aryl, -C(O)-O-Cj_ 6 alkyl, or -C(O)-O-optionally substituted aryl. Preferably, the amino terminus protecting group is acetyl, propyl, succinyl, benzyl, benzyloxycarbonyl or t- butyloxycarbonyl. A protecting group covalently joined to the C-terrmnal carboxy group reduces the reactivity of the carboxy terminus under in vivo conditions. The carboxy terminus protecting group is preferably attached to the α-carbonyl group of the last amino acid. Carboxy terminus protecting groups include amide, methylamide, and ethyl amide. "Alkyl" refers to carbon atoms joined by carbon-carbon single bonds. The alkyl hydrocarbon group may be straight-chain or contain one or more branches or cyclic groups. Preferably, the alkyl group is 1 to 4 carbons in length. Examples of alkyl include methyl, ethyl, propyl, isopropyl, cyclopropyl, butyl, and t-butyl. Alkyl substituents are selected from the group consisting of halogen (preferably -F or -Cl) -OH, -CN, -SH, -NH 2 , -NO 2 , -C 1-2 alkyl substituted with 1 to 6 halogens (preferably -F or -Cl, more preferably -F), -CF 3 , -OCH 3 , or -OCF 3 . "Alkenyl" refers to a hydrocarbon group containing one or more carbon-carbon double bonds. The alkenyl hydrocarbon group may be straight-chain or contain one or more branches or cyclic groups. Preferably, the alkenyl group is 2 to 4 carbons in length. Alkenyl substituents are selected from the group consisting of halogen (preferably -F or -Cl), -OH, -CN, -SH, -NH 2 , -NO 2 , -C,. 2 alkyl substituted with 1 to 5 halogens (preferably -F or -Cl, more preferably -F), -CF 3 , -OCH 3 , or -OCF 3 . "Aryl" refers to an optionally substituted aromatic group with at least one ring having a conjugated pi- electron system, containing up to two conjugated or fused ring systems. Aryl includes carbocyclic aryl, heterocyclic aryl and biaryl groups. Preferably, the aryl is a 5 or 6 membered ring, more preferably benzyl. Aryl substituents are selected from the group consisting of -C 1-4 alkyl, -C 1-4 alkoxy, halogen (preferably -F or -Cl), -OH, -CN, -SH, -NH 2 , -NO 2 , -Cj. 2 alkyl substituted with 1 to 5 halogens (preferably -F or -Cl, more preferably -F), -CF 3 , or -OCF 3 . A labeled derivative indicates the alteration of a substituent with a detectable label. Examples of detectable labels include luminescent, enzymatic, and radioactive labels. A prefeπed radiolabel is 125 I. Both the type of label and the position of the label can effect MCH activity. Labels should be selected so as not to substantially alter the activity of the truncated MCH analog at the MCH receptor. The effect of a particular label on MCH activity can be determined using assays measuπng MCH activity and/or binding. In naturally occurπng full length MCH, alteration of the tyrosine at position 13 by labeling with 125 I substantially effects MCH activity. (Drozdz, et al., 1995. FEBS letters 359, 199-202 ) 125 I labeled analogs of full length mammalian MCH having substantial activity can be produced, for example, by replacing the tyrosine at position 13 with a different group, then replacing vahne at position 19 with tyrosme, and labeling the tyrosine Examples of such analogs include Tryl9]-MCH and (D-(p-benzoylphenylalanιne)13, tyrosme 19)-MCH. (Drozdz, et al , FEBS letters 359, 199-202, 1995; and Drozdz, et al, J. Peptide Sci 5, 234-242, 1999 ) In prefeπed embodiments the optionally modified peptide has the structure i 1 Zl- X6-χ7 χ8-χ9-χl0-χl l-χl2-χl3-χl4-χl5-χl6-χl7-z2 wherein the different groups, and preferred groups, are as descπbed above. In different embodiments the truncated MCH analog is a peptide of SEQ. ID. NOS. 7, 8, 9, or 10, a labeled deπvative of said peptide or a pharmaceutically acceptable salt of said peptide or of said labeled deπvative. SEQ. ID. NOS. 7-12 are made up of L-ammo acids and have the following sequences ("*" indicates cyclization (S-S)) SEQ. ID. NO. 7: Ac-Arg-Cys-Met-Leu-Gly-Arg-Val-Tyr-Arg-Pro-Cys-amide; * * SEQ. ID. NO. 8: Ac-Arg-Cys-Met-Leu-Gly-Arg-Val-Phe-Arg-Pro-Cys-Tyr-arnide; * * SEQ. ID. NO. 9: Ac-Cys-Met-Leu-Gly-Arg-Val-Tyr-Arg-Pro-Cys-armde; SEQ. ID. NO. 10: ^ x Asp-Phe-Asp-Met-Leu-Arg-Cys-Met-Leu-Gly-Arg-Val-Tyr-Arg-Pro-Cys-amide; SEQ. ID. NO. 12: Ac-Cys-Met-Leu-Gly-Arg-Val-Tyr-Arg-Pro-Cys-Trp-Gln-Val; SEQ. ID. NO. 13: Asp-Phe-Asp-Nle-Leu-Arg-Cys-Nle-Leu-Gly-Arg-Val-Tyr-Arg-Pro-Cys-T -Gln- Val; SEQ. ID. NO. 14: Asp-Phe-Ala-Met-Leu-Arg-Cys-Met-Leu-Gly-Arg-Val-Phe-Arg-Pro-Cys-Trp-Gln- Tyr. In additional embodiments the peptide has a sequence selected from the group consisting of SEQ. ID. NOs. 7, 8, 10, 15, 24, 25, 27, 28, 30-49, 51, 52, 56, 57, 61, 62, 63, 65-67, 69-72, and 77, is a labeled derivative of said peptide or a pharmaceutically acceptable salt of said peptide or of said labeled derivative. Prefeπed sequences are those with an IC50 less than 0.3 nM, preferably less than 0.1 nM; and/or those having a % activation greater than about 90%, preferably greater than 100%. Examples of prefeπed sequences are provided in Example 4, Tables 1-7. Truncated MCH analogs can be produced using techniques well known in the art. For example, a polypeptide region of a truncated MCH analog can be chemically or biochemically synthesized and, if desired modified to produce a blocked N-terminus and/or blocked C-terminus. Techniques for chemical synthesis of polypeptides are well known in the art. (See e.g., Vincent, in Peptide and Protein Drug Delivery, New York, N.Y., Dekker, 1990.) Examples of techniques for biochemical synthesis involving the introduction of a nucleic acid into a cell and expression of nucleic acids are provided in Ausubel, Current Protocols in Molecular Biology, John Wiley, 1987-1998, and Sambrook, et al, in Molecular Cloning, A Laboratory Manual, 2 nd Edition, Cold Spring Harbor Laboratory Press, 1989. MCH Receptor Binding Assay Assays measuring the ability of a compound to bind a MCH receptor employ a MCH receptor, a fragment of the receptor comprising a MCH binding site, a polypeptide compπsing such a fragment, or a deπvative of the polypeptide Preferably, the assay uses the MCH receptor or a fragment thereof A polypeptide compπsing a MCH receptor fragment that binds MCH can also contain one or more polypeptide regions not found in a MCH receptor A derivative of such a polypeptide compπses a MCH receptor fragment that binds MCH along with one or more non-peptide components The MCH receptor amino acid sequence involved m MCH binding can be readily identified using labeled MCH or truncated MCH analogs and different receptor fragments Different strategies can be employed to select fragments to be tested to naπow down the binding region Examples of such strategies include testing consecutive fragments about 15 ammo acids in length starting at the N-termmus, and testing longer length fragments If longer length fragments are tested, a fragment binding MCH can be subdivided to further locate the MCH binding region Fragments used for binding studies can be generated using recombinant nucleic acid techniques Binding assays can be performed using individual compounds or preparations containing different numbers of compounds A preparation containing different numbers of compounds having the ability to bind to the MCH receptor can be divided into smaller groups of compounds that can be tested to identify the compound(s) binding to the MCH receptor In an embodiment of the present invention a test preparation containing at least 10 compounds is used in a binding assay Binding assays can be performed using recombmanfly produced MCH receptor polypeptides present in different environments Such environments include, for example, cell extracts and puπfied cell extracts containing the MCH receptor polypeptide expressed from recombinant nucleic acid or naturally occurπng nucleic acid; and also include, for example, the use of a puπfied MCH receptor polypeptide produced by recombinant means or from naturally occurπng nucleic acid v, hich is introduced into a different environment. Screening for MCH Receptor Active Compounds Screening for MCH active compounds is facilitated using a recombinantly expressed MCH receptor Using recombinantly expressed MCH receptor polypeptides offers several advantages such as the ability to express the receptor in a defined cell system so that response to MCH receptor active compounds can more readily be differentiated from responses to other receptors. For example, the MCH receptor can be expressed m a cell line such as HEK 293, COS 7, and CHO not normally expressing the receptor by an expression vector, wherein the same cell line without the expression vector can act as a control. Screening for MCH receptor active compounds is facilitated through the use of a truncated MCH analog in the assay. The use of a truncated MCH analog in a screening assay provides for MCH receptor activity. The effect of test compounds on such activity can be measured to identify, for example, allosteπc modulators and antagonists. Additionally, such assays can be used to identify agonists MCH receptor activity can be measured using different techniques such as detecting a change in the mtracellular conformation of the MCH receptor, Gi or Gq activity, and/or mtracellular messengers. Gi activity can be measured using techniques well known in the art such as a melonaphore assay, assays measuπng cAMP production, inhibition of cAMP accumulation, and binding of 35S-GTP. cAMP can be measured using different techniques such as radioimmunoassay and indirectly by cAMP responsive gene reporter proteins. Gq activity can be measured using techniques such as those measuπng mtracellular Ca + . Examples of techniques well known in the art that can be employed to measure Ca 2+ include the use of dyes such as Fura-2 and the use of Ca 2+ -bιolumιnescent sensitive reporter proteins such as aequoπn. An example of a cell line employing aequoπn to measure G-protem activity is HEK293/aeql7. (Button, et al, 1993. Cell Calcium 14, 663-671, and Feighner, et al , 1999. Science 284, 2184-2188, both of which are hereby incorporated by reference herein ) Chimeπc receptors containing a MCH binding region functionally coupled to a G protein can also be used to measure MCH receptor activity A chimeπc MCH receptor contains an N-termmal extracellular domain; a transmembrane domain made up of transmembrane regions, extracellular loop regions, and mtracellular loop regions; and an mtracellular carboxy terminus. Techniques for producing chimeπc receptors and measuπng G protein coupled responses are provided for m, for example, International Application Number WO 97/05252, and U.S. Patent Number 5,264,565, both of which are hereby incorporated by reference herein. Weight or Appetite Alteration Truncated MCH analogs can be used m methods to increase or maintain weight and/or appetite in a subject Such methods can be used, for example, as part of an expeπmental protocol examining the effects of MCH antagonists, to achieve a beneficial effect in a subject and/or to further examine the physiological effects of MCH. Expeπmental protocols examining the effects of MCH antagonists can be performed, for example, by using a sufficient amount of a truncated MCH analog to produce a weight or appetite increase in a subject and then examining the effect of a test compound Changes m weight and appetite can be measured using techniques well known in the art Increasing weight or appetite can be useful for maintaining weight or producing a weight or appetite gam in an under weight subject, or in a patient having a disease or undergoing treatment that effects weight or appetite. In addition, for example, farm animals such as pigs, cows and chickens can be treated to gam weight Under weight subjects include those having a body weight about 10% or less, 20% or less, or 30% or less, than the lower end of a "normal" weight range or Body Mass Index ("BMI"). "Normal" weight ranges are well known m the art and take into account factors such as a patient age, height, and body type. BMI measures your height/weight ratio It is determined by calculating weight in kilograms divided by the square of height in meters. The BMI "normal" range is 19-22. Administration Truncated MCH analogs can be formulated and administered to a subject using the guidance provided herein along with techniques well known in the art. The preferred route of administration ensures that an effective amount of compound reaches the target. Guidelines for pharmaceutical administration in general are provided in, for example, Remington 's Pharmaceutical Sciences 18 " Edition, Ed Gennaro, Mack Publishing, 1990, and Modem Pharmaceutics 2 n Edition, Eds Banker and Rhodes, Marcel Dekker, Inc , 1990, both of which are hereby incorporated by reference herein Truncated MCH analogs can be prepared as acidic or basic salts Pharmaceutically acceptable salts (in the form of water- or oil-soluble or dispersible products) include conventional non-toxic salts or the quaternary ammonium salts that are formed, e.g., from inorganic or organic acids or bases. Examples of such salts include acid addition salts such as acetate, adipate, alginate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, citrate, camphorate, camphorsulfonate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, fumarate, glucoheptanoate, glycerophosphate, hemisulfate, heptanoate, hexanoate, hydrochloπde, hydrobromide, hydroiodide, 2-hydroxyethanesulfonate, lactate, maleate, methanesulfonate, 2-naphthalenesulfonate, mcotmate, oxalate, pamoate, pectinate, persulfate, 3-phenylpropιonate, picrate, pivalate, propionate, succinate, tartrate, thiocyanate, tosylate, and undecanoate, and base salts such as ammonium salts, alkali metal salts such as sodium and potassium salts, alkaline earth metal salts such as calcium and magnesium salts, salts with organic bases such as dicyclohexylamme salts, N-methyl-D-glucamme, and salts with amino acids such as argmine and lysine. Truncated MCH analogs can be administered using different routes including oral, nasal, by injection, transdermal, and transmucosally. Active ingredients to be administered orally as a suspension can be prepared according to techniques well known m the art of pharmaceutical formulation and may contain microcrystalhne cellulose for imparting bulk, algmic acid or sodium alginate as a suspending agent, methylcellulose as a viscosity enhancer, and sweeteners/flavoπng agents. As immediate release tablets, these compositions may contain microcrystalhne cellulose, dicalcium phosphate, starch, magnesium stearate and lactose and/or other excipients, binders, extenders, dismtegrants, diluents and lubπcants Truncated MCH analogs may also be administered in intravenous (both bolus and infusion), mtrapeπtoneal, subcutaneous, topical with or without occlusion, or intramuscular form. When administered by injection, the injectable solution or suspension may be formulated using suitable non-toxic, parenterally-acceptable diluents or solvents, such as Ringer's solution or isotonic sodium chloπde solution, or suitable dispersing or wetting and suspending agents, such as steπle, bland, fixed oils, including synthetic mono- or diglyceπdes, and fatty acids, including oleic acid. Suitable dosmg regimens are preferably determined taking into factors well known in the art including type of subject being dosed; age, weight, sex and medical condition of the subject; the route of administration; the renal and hepatic function of the subject; the desired effect, and the particular compound employed Optimal precision in achieving concentrations of drug withm the range that yields efficacy without toxicity requires a regimen based on the kinetics of the drug's availability to target sites. This involves a consideration of the distπbution, equihbπum, and elimination of a drug. The daily dose for a subject is expected to be between 0.01 and 1,000 mg per subject per day. Truncated MCH analogs can be provided in kit. Such a kit typically contains an active compound in dosage forms for administration. A dosage form contains a sufficient amount of active compound such that a weight or appetite increase can be obtained when administered to a subject duπng regular intervals, such as 1 to 6 times a day, duπng the course of 1 or more days. Preferably, a kit contains instructions indicating the use of the dosage form for weight or appetite increase and the amount of dosage form to be taken over a specified time peπod. EXAMPLES Examples are provided below to further illustrate different features of the present invention. The examples also illustrate useful methodology for practicing the invention. These examples do not limit the claimed invention. Example 1 : Synthesis of MCH Analogs MCH analogs were produced using the procedures descπbed below and varying the stepwise addition of ammo acid groups. Other procedures for producing and modifying peptides are well known in the art. Elongation of peptidyl chains on 4-(2',4'-dιmethoxyphenyl-Fmoc- amιnomethyl)-phenoxy resin and the acetylation of the N-termmal ammo groups of the peptides was performed on a 431 A ABI peptide synthesizer. Manufacture- supplied protocols were applied for coupling of the hydroxybenzotπazole esters of amino acids in N-methylpyπohdone (NMP). The fluorenylmethyloxycarbonyl (Fmoc) group was used as a semipermanent alpha-ammo protecting group, whereas the side chains protecting groups were: tert-butyl for aspartic acid and tyrosme, 2,2,4,6,7-pentamethyldιhydrobenzofuran-5-sulfonyl (Pbf) for argmine, and tπtyl for cysteine. Peptides were cleaved from the resm with TFA containing 5 % of anisole. After 2 hours at room temperature the resin was filtered, washed with TFA and the combined filtrates were evaporated to dryness in vacuo. The residue was tπturated with ether, the precipitate which formed was filtered oft. washed with ether, and dπed. Crude peptides were dissolved in 5 % acetic acid m water, and the pH of the solutions were adjusted to ca 8.2 with diluted ammonium hydroxide. The reaction mixtures were stiπed vigorously while 0.05 % solution of potassium femcyanide (K3Fe(CN)g) in water was added dropwise till the reaction mixture remained yellow for about 5 minutes. After an additional 20 minutes oxidation was terminated with ca. 1 ml of acetic acid and the reaction mixtures were lyophihzed Crude lyophihzed peptides were analyzed by analytical reverse-phase high-pressure liquid chromatography (RP HPLC) on a C18 Vydac column attached to a Waters 600E system with automatic Wisp 712 injector and 991 Photodiode Array detector. A standard gradient system of 0-100% buffer B in 30 minutes was used for analysis: buffer A was 0 1% tπfluoroacetic acid in water and buffer B was 0.1% tπfluoroacetic acid in acetonitπle HPLC profiles were recorded at 210 nm and 280 nm. Preparative separations were performed on a Waters Delta Prep 4000 system with a semipreparative C18 RP Waters column. The above-descπbed solvent system of water and acetomtπle. in a gradient of 20-80 % buffer B m 60 minutes, was used for separation. The chromatographically homogenous compounds were analyzed by electrospray mass spectrometry. Example 2: Aequoπn Biolummescence Functional Assay The aequoπn biolummescence assay is a reliable test for measuπng the activity of G protein-coupled receptors that couple through the Gα protein subumt family consisting of Gq and GI 1 and leads to the activation of phosphohpase C, mobilization of mtracellular calcium and activation of protein kinase C Measurement of MCH receptor activity in the aequoπn-expressing stable reporter cell line 293-AEQ17 (Button et al, Cell Calcium 74:663-671, 1993) was performed using a Lummoskan RT lummometer (Labsystems Inc., Gaithersburg, MD). 293-AEQ17 cells (8 x 10 5 cells plated 18 hours before transfection in a T75 flask) were transfected with 22 μg of human MCH receptor plasmid using 264 μg hpofectamine. The open reading frame cDNA (SEQ. ID NO. 1) encoding the human MCH receptor inserted m the mammalian expression vector pcDNA-3 (Invitrogen, Carlsbad, CA) was used for expression studies Following approximately 40 hours of expression the apo-aequoπn in the cells was charged for 4 hours \\ ith coelenterazme (10 μM) under reducing conditions (300 μM reduced glutathione) in ECB buffer (140 mM NaCl, 20 mM KC1, 20 mM HEPES-NaOH [pH=7.4], 5 mM glucose, 1 mM MgCl2, 1 mM CaCl2, 0.1 mg/ml bovme serum albumin). The cells were harvested, washed once in ECB medium and resuspended to 500,000 cells/ml 100 μl of cell suspension (coπespondmg to 5xl0 4 cells) was then injected into the test plate containing MCH or MCH analogs, and the integrated light emission was recorded over 30 seconds, in 0.5 second units. 20 μL of lysis buffer (0.1% final Tπton X-100 concentration) was then injected and the integrated light emission recorded over 10 seconds, in 0.5 second units. The "fractional response" values for each well were calculated by taking the ratio of the integrated response to the initial challenge to the total integrated luminescence including the Tπton X-100 lysis response Example 3: Radiolabeled MCH-R Binding Assay Activity of truncated MCH analogs was assayed by measuπng the ability of the analog to inhibit binding of [ 125 l] -human MCH (Phe 13 , Tyr 19 substituted) to membranes prepared from cells stably expressing the human MCH receptor. Human MCH (Phe 13 , Tyr 19 substituted) used in the assay was radiolabeled with 125 l at 19 Tyr to a specific activity of -2000 Ci/mmol (NEN Life Science Products, Boston, MA). Cell membranes were prepared on ice. Each T-75 flask was πnsed twice with 10 ml of Enzyme-free Cell Dissociation Buffer (Specialty Media, Lavallette, NJ), and the cell monolayer was detached in an additional 10 ml of Enzyme-free Cell Dissociation Buffer by incubation at room temperature for 10 minutes. Dissociated cells were centπfuged (500 x g for 10 minutes at 4°C), resuspended in 5 ml homogemzation buffer (10 mM Tπs-HCl, pH 7.4, 0.01 mM Pefabloc, 10 μM phosphoramidon, 40 μg/ml bacitracin) and then homogenized using a glass homogenizer (10-15 strokes). The homogenate was centπfuged for 10 minutes (1,000 x g at 4°C). The resulting supernatant was then centπfuged at 38,700 x g for 15 minutes at 4°C. Pelleted membranes were resuspended (passed through 25 gauge needle 5 times), snap-frozen on liquid nitrogen, and stored at -80°C until use Binding was performed in a 96-well filter assay or Scintillation Proximity Assay (SPA)-based format using cell membranes from a stable CHO or HEK-293 cell line expressing the MCH receptor. For the filter assay, reactions were performed at 20°C for 1 hour in a total volume of 0.2 ml containing: 0 05 ml of membrane suspension (~3 μg protein), 0.02 ml of [ 125 I]-human MCH (Phe 13 , Tyr 19 substituted; 30 pM), 0.01 ml of competitor and 0.12 ml of binding buffer (50 mM Tris-HCl, pH 7.4, 10 mM MgCl2, 2 mM EDTA, 200 μg/ml bacitracin, 1 μM phosphoramidon). Bound radioligand was separated by rapid vacuum filtration (Packard Filtermate 96-well cell harvester) through GF/C filters pretreated for 1 hour with 1 % polyethylenimine. After application of the membrane suspension to the filter, the filters were washed 3 times with 3 ml each of ice-cold 50 mM Tris-HCl, pH 7.4, 10 mM MgCl2, 2 mM EDTA, 0.04 % Tween 20 and the bound radioactivity on the filters was quantitated by scintillation counting (TopCount device). Specific binding (>80 % of total) is defined as the difference between total binding and non-specific binding conducted in the presence of 100 nM unlabeled human MCH. For the SPA-based assay, WGA-PVT beads (NEN Life Sciences Products) were resuspended in Dulbecco's PBS with calcium and magnesium (500 mg beads in 4 ml PBS). For each 96-well assay plate, 0.18 ml of beads was pre- coated with MCH receptor by mixing with 0.2 ml MCH receptor CHO cell membranes (~ 0.2-4 mg protein) and 1.5 ml SPA assay buffer (50 mM Tris-HCl, pH 7.4, 10 mM MgC , 2 mM EDTA, 0.1 % BSA, 12 % glycerol). The suspension was mixed gently for 20 minutes, 12.3 ml of assay buffer and protease inhibitors were added (final concentration given): 2 μg/ml leupeptin, 10 μM phosphoramidon, 40 μg/ml bacitracin, 5 μg/ml aprotinin, 0.1 mM Pefabloc. Coated beads were kept on ice until use. For each well, 0.145 ml of beads were added to Optiplate assay plates (Packard 6005190), followed by 0.002- 0.004 ml of competitor and 0.05 ml of [ 125 I]-human MCH (Phe 13 , Tyr 19 substituted; 30 pM). Binding reactions were allowed to proceed at room temperature for 3 hours. Quantitation was performed by scintillation counting (TopCount device). Example 4: MCH Activity The activity of different MCH analogs was measured using the procedures described in Examples 2 and 3 above. Tables 1-7 illustrate the activity of different truncated MCH analogs and mammalian MCH (SEQ. ID. NO. 11). Figure 1 illustrates the results of replacing different amino acids of mammalian MCH with alanine. Based on the guidance provided herein, additional MCH analogs active at the MCH receptor can be obtained. TABLE 1 IC50 was determined using a SPA based assay. EC50 (nM) and % Activation at 10 μM were determined using aequorin functional assays Table 2 illustrates the affect of different D-amino acids. TABLE 2 Table 3 illustrates the effect of different N-methyl-amino acids. TABLE 3 Table 4 illustrates the affect of different alterations to position 6 of the SEQ. ID. NO. 7 MCH analog. TABLE 4 Table 5 illustrates the affect of different alterations to position 10 of the SEQ. ID. NO. 7 MCH analog. TABLE 5 Table 6 illustrates the affect of different alterations to position 13 of the SEQ. ID. NO. 7 MCH analog. TABLE 6 Table 7 illustrates the affect of some alteration combinations and some alterations to position 8 of the SEQ. ID. NO. 7 MCH analog. TABLE 7 Other embodiments are within the following claims. While several embodiments have been shown and described, various modifications may be made without departing from the spirit and scope of the present invention.

Claims: WHAT IS CLAIMED IS 1. An optionally substituted peptide having the structure- Zl- χl-χ2-χ3.χ4-χ5-χ6-χ7 χ8-χ9.χl0-χl l-χl2.χl3-χl4.χl5-χl6.χl7- Z 2 herein Xl is an optionally present ammo acid that, if present, is either alanine, valine, leucine. isoleucine, prohne, tryptophan, phenylalanine, methionine, glycine, seπne, threonme, tyrosme, cysteine, asparagme, glutamme, lysine, arginme, histidme, aspartic acid, or glutarmc acid, or a derivative thereof. χ2 is an optionally present amino acid that, if present, is either alanine, valine, leucme, isoleucine, prohne, tryptophan, phenylalanine, methionine, glycme, seπne, threonme, tyrosine, cysteine, asparagme, glutamme, lysine, arginine, histidme, aspartic acid, or glutarmc acid, or a deπvative thereof; X3 is an optionally present amino acid that, if present, is either alanine, valine, leucine, isoleucine, prohne, tryptophan, phenylalanme, methiomne, glycine, seπne, threonme, tyrosine, cysteine, asparagme, glutamme, lysine, arginine, histidine, aspartic acid or glutarmc acid, or a deπvative thereof; χ4 is an optionally present amino acid that, if present, is either alanme, valine, leucine, isoleucine, proline, tryptophan, phenylalanine, methionine, glycme, seπne, threonme, tyrosine, cysteine, asparagme, glutamme, lysine. arginine, histidme, aspartic acid, glutamic acid, or norleucme, or a derivative thereof. χ5 is an optionally present ammo acid that, if present, is either alanine, vahne, leucine, isoleucine, prohne, tryptophan, phenylalanine, methionine, glycine, seπne, threonme, tyrosine, cysteine, asparagme, glutamme, lysine. arginine, histidme, aspartic acid or glutarmc acid, or a deπvative thereof, χ6 is an optionally present ammo acid that, if present is either arginine, alanine, leucine, glycme, lysine, prohne, asparagme, seπne, histidine, nitroargmine, norleucme, or des-amino-argmme, or a deπvative thereof, χ7 is either cysteine, homocysteine, or pemcillamine, or a deπvative thereof; χ8 is either methionine, norleucme, leucine, isoleucine, vahne, methioninesulfoxide, or methionmesulfone, or a deπvative thereof; χ9 is either leucine, isoleucine, vahne, alanine, methionine, or 5- aminopentanoic acid, or a deπvative thereof, XlO is either glycme, alanme, leucine, norleucme, cyclohexylalamne, 5-ammopentanoιc acid, asparagme, serme, sarcosme, isobutyπc, or gamma- ammobutyπc acid, or a deπvative thereof; Xl 1 is either argmine, lysine, citrulhne, histidme, or mtroarginme, or a deπvative thereof, Xl2 1S either valine, leucme, isoleucine, alanme, or methionine, or a deπvative thereof; Xl3 1S either phenylalanme, tyrosine, D-( -benzoylphenylalamne), tryptophan, (1')- and (2')-naphthylalanme, cyclohexylalamne, or mono and multi- substituted phenylalanine wherein each substituent is independently selected from the group consisting of O-alkyl, alkyl, OH, NO2, NH2, F, I, and Br; or a deπvative thereof; Xl4 is either arginine, lysme, histidme, norargmme, or 5- ammopentanoic acid or a deπvative thereof, X 5 is either proline, alanine, valine, leucine, isoleucine, methionine, sarcosine, or 5-amιnopentanoιc acid, or a deπvative thereof; Xl6 is either cysteine, homocysteine, or pemcillamine, or a deπvative thereof, Xl7 is an optionally present amino acid that, if present, is either alanme, valine, leucine, isoleucine, prohne, tryptophan, phenylalanme, methionine, glycme, seπne, threonme, tyrosine, cysteine, asparagme, glutamme, lysine, arginine, histidine, aspartic acid or glutamic acid, or a deπvative thereof; Zl is an optionally present protecting group that, if present, is covalently joined to the N-terminal amino group; Z2 is an optionally present protecting group that, if present, is covalently joined to the C-termmal carboxy group; or a labeled deπvative of said peptide; or a pharmaceutically acceptable salt of said peptide or of said labeled deπvative. 2. The peptide of claim 1, wherein Xl, χ , χ3, χ4, and χ5 are not present; χ6 is arginine; and Xl7 is tyrosine or tryptophan. 3. The peptide of claim 1, wherein Xl, χ2, χ3, χ4, χ5, and Xl7are not present; and χ6 is argmine 4. The peptide of claim 3, wherein X is -C(O)CH3 and Z2 is -NH2. 5. The peptide of claim 1, wherein said peptide is either SEQ. ID. NO. 7, SEQ. ID. NO. 8, SEQ. ID NO. 9, SEQ. ED NO. 10, or a pharmaceutically acceptable salt thereof. 6 The peptide of claim 1, wherein said peptide is either SEQ. ID. NO. 7, SEQ. ID. NO. 8, or a pharmaceutically acceptable salt thereof 7. The peptide of claim 1, wherein Xl, χ2, χ3, χ4, χ5 a nd χl7 are not present; χ6 is either argmine, D-argimne, D-norleucine, D-prohne, D-seπne, or D-asparagme; χ7 is cysteine; χ8 is either methionine, norleucme, or N-methyl norleucme; χ9 is leucine; XlO is either glycine, alanine, leucine, norleucme, asparagme, seπne, D-norleucme, D-prohne, gamma-aminobutyπc acid, or sarcosine; Xl l is arginine, Xl2 is vahne; Xl3 is phenylalanine, (2')napthylalanιne, p-fluoro-phenylalanine, tyrosine, or cyclohexylalamne ; Xl4 is arginine; Xl5 γ$, either proline or sarcosine; and χl6 is either cysteine or D-cysteme. 8. The peptide of claim 1, wherein said peptide consists of a sequence selected from the group consisting of: 7, 8, 10, 15, 24, 25, 27, 28, 30-49, 51, 52, 56, 57, 61, 62, 63, 65-67, 69-72, and 77. 9. A method of screening for a compound able to bind a MCH receptor compπsing the step of measuπng the ability of said compound to effect binding of the peptide of any one of claims 1-8 to either said receptor, a fragment of said receptor compπsing a MCH binding site, a polypeptide compπsing said fragment, or a deπvative of said polypeptide. 10. The method of claim 9, wherein said method measures the ability of said peptide to bind to said receptor or said fragment thereof. 11. The method of claim 10, wherein said peptide is radiolabeled 12. The method of claim 9, wherein said peptide is a radiolabeled deπvative of SEQ. ID. NO 8 or a pharmaceutically acceptable salt thereof. 13. A method for increasing weight m a subject compπsing the step of administeπng to said subject an effective amount of the peptide of any one of claims 1-8 to produce a weight increase. 14. A method for increasing appetite in a subject compπsing the step of admmisteπng to said subject an effective amount of the peptide of any one of claims 1-8 to produce an appetite increase. 15. A method for measuπng the ability of a compound to decrease weight or appetite m a subject compπsing the steps of: a) administeπng to said subject an effective amount of the peptide of any one of claims 1-8 to produce a weight increase or appetite increase, b) administeπng said compound to said subject, and c) measuπng the change m weight or appetite of said subject. 16. The method of claim 15, wherein said subject is either a rat or a mouse.

Inventors: BEDNAREK MARIA, BEDNAREK, MARIA
Applicants: BEDNAREK MARIA, MERCK & CO INC, BEDNAREK, MARIA, MERCK & CO., INC.
Application year: 2001
Main classification: C07K7
IPC codes: A61K38, A61P1, C07K7, C07K14, G01N33