Biological active ligands of melanocortin receptors

Details Biological active ligands of melanocortin receptors Biological active ligands of melanocortin receptors

2007-04-09

2011-11-15

Landsman, Robert (Department: 1647)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Peptide containing doai

C530S317000

Reexamination Certificate

active

08058240

ABSTRACT:
Disclosed are novel ligands based on an AGRP template that can rescue endogenous melanocortin agonist and/or antagonist dysfunction at MCR polymorphisms. In particular, the present invention provides novel synthetic ligands based on AGRP templates that can rescue endogenous melanocortin agonist dysfunction at MC4R polymorphisms to treat children and adults with these mutations and increase their quality of life.

REFERENCES:
patent: 2004/0260063 (2004-12-01), Haskell-Luevano
Branson, R. et al., “Binge Eating as a Major Phenotype of Melanocortin 4 Receptor Gene Mutations,”N. Engl. J. Med., Mar. 20, 2003, vol. 348, No. 12, pp. 1096-1103.
Chai, B-X. et al, “Inverse agonist activity of agouti and agnuti-related protein,”Peptides, 2003, vol. 24, No, 4, pp. 603-609.
Chen, W. et al., “A Calorimetric Assay for Measuring Activation of Gs- and Gq-Coupled Signaling Pathways,”Analytical Biochemistry, Apr. 1995, vol. 226, No. 2, pp. 349-354.
Chen, W. et al., “Exocrine gland dysfunction in MC5-R-deficient mice: evidence for coordinated regulation of exocrine gland function by melanocortin peptides,”Cell, 1997, vol. 91, pp. 789-798.
Dubern, B. et al., “Mutational analysis of melanocortin-4 receptor, agouti-related protein, and α-melanocyte-stimulating hormone genes in severely obese children,”J. Pediatr., Aug. 2001, vol. 139, No. 2, pp. 204-209.
Eipper, B.A. et al., “Structure and Biosynthesis of Pro-Adrenocorticotropin/Endorphin and Related Peptides,”Endocrine Reviews, Mar. 1980, vol. 1, No. 1, pp. 1-27, Abstract only.
Fan, W. et al., “Role of melanocortinergic neurons in feeding and theagoutiobesity syndrome,”Nature, 1997, vol. 385, pp. 165-168.
Farooqi, I.S. et al., “Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene,”N. Engl. J. Med., 2003, vol. 348, No. 12, pp. 1085-1095.
Farooqi, I.S. et al., “Dominant and recessive inheritance of morbid obesity associated with melanocortin 4 receptor deficiency,”J. Clin. Invest., 2000, vol. 106, No. 2, pp. 271-279.
Haskell-Luevano, C. et al., “Agouti-related protein functions as an inverse agonist at a constitutively active brain melanocortin-4 receptor,”Regulatory Peptides, 2001, vol. 99, pp. 1-7.
Haskell-Luevano, C. et al., “Structure Activity of the Melanocortin-4 Receptor in Vitro Mutagenesis: Identification of Agouti-Related Protein (AGRP), Melanocortin Agonist and Synthetic Peptide Antagonist Interaction Determinants,”Biochemistry, Apr. 2001, vol. 40, pp. 6164-6179.
Haskell-Luevano, C. et al., “The agouti-related protein decapeptide (Yc[CRFFNAFC]Y) possesses agonist activity at the murine melanocortin-1 receptor,”Peptides, 2000, vol. 21, pp. 683-689.
Hinney, A. et al., “Melanocortin-4 Receptor Gene: Case-Control Study and Transmission Disequilibrium Test Confirm that Functionally Relevant Mutations are Compatible with a Major Gene Effect for Extreme Obesity,”J. Clin. Endocrinol. Metab., Sep. 2003, vol. 88. No. 9, pp. 4258-4267.
Hinney, A. et al., “Several mutations in the melanocortin-4 receptor gene including a nonsense and a frameshift mutation associated with dominantly inherited obesity in humans,”J. Clin. Endocrinol. Metab., 1999, vol. 84, No. 4, pp. 1483-1486.
Hinney, A. et al., “Systematic mutation screening of the Pro-Opiomelanocortin Gene: Identification of Several Genetic Variants including three different insertions, one nonsense and two missense point mutations in probands of different weight extremes,”J. Clin. Endocrinol. Metab., 1998, vol. 83, No. 10, pp. 3737-3741.
Ho, G. et al., “Functional Characterization of Mutations in Melanocortin-4 Receptor Associated with Human Obesity,”J. Biol. Chem., Dec. 10, 1999, vol. 274, No, 50, pp. 35819-35822.
Huszar, D. et al., “Targeted disruption of the melanocortin-4 receptor results in obesity in mice,”Cell, 1997, vol. 88, pp. 131-141.
Kask, A. et al., “Selective antagonist for the melanocortin-4 receptor (HS014) increases food intake in free-feeding rats,”Biochem. Biophys. Res. Commun., 1998, vol. 245, pp. 90-93.
Kiefer, L. et al., “Mutations in the carboxyl terminus of the agouti protein decrease agouti inhibition of ligand binding to the melanocortin receptors,”Biochemistry, 1997, vol. 36, pp. 2084-2090.
Krude, H. et al., “Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused byPOMCmutations in humans,”Nat. Genet., 1998, vol. 19, No. 2, pp. 155-157.
Larsen, L. H. et al., “Prevalence of Mutations and Functional Analyses of Melanocortin 4 Receptor Variants Identified among 750 Men with Juvenile-Onset Obesity,”J. Clin. Endocrinol. Metab., 2005, vol. 90, No. 1, pp. 219-224.
Lubrano-Berthelier, C. et al., “Intracellular retention is a common characteristic of childhood obesity-associated MC4R mutations,”Human Molecular Genetics, 2003, vol. 12, No. 2, pp. 145-153.
Nijenhuis, W.A. et al., “AgRP(83-132) acts as an inverse agonist on the human-melanocortin-4 receptor,”Mol. Endocrinol., 2001, vol. 15, No. 1, pp. 164-171.
Ollmann, M.M. et al., “Antagonism of Central Melanocortin Receptors in Vitro and in Vivo by Agouti-related protein,”Science, 1997, vol. 278, pp. 135-138.
Smith, A.I. et al., “Proopiomelanocortin Processing in the Pituitary, Central Nervous System, and Peripheral Tissues,”Endocrine Reviews, 1988, vol. 9, pp. 159-179, Abstract only.
Tota, M.R. et al., “Molecular interaction of Agouti protein and Agouti-related protein with human melanocortin receptors,”Biochemistry, 1999, vol. 38, pp. 897-904.
Vaisse, C. et al., “Melanocortin-4 receptor mutations are a frequent and heterogeneous cause of morbid obesity,”J. Clin. Invest., 2000, vol. 106, No. 2, pp. 253-262.
Vaisse, C. et al., “A frameshift mutation in humanMC4Ris associated with a dominant form of obesity,”Nat Genet, 1998, vol. 20, No. 2, pp. 113-114.
Wilczynski, A.M. et al., “Current Trends in the Structure-Activity Relationship Studies of the Endogenous Agouti-Related Protein (AGRP) Melanocortin Receptor Antagonist,”Medicinal Research Reviews, 2005, vol. 25, No. 5, pp. 545-556.
Wilczynski, A. et al., “Identification of Putative Agouti-Related Protein(87-132)-Melanocortin-4 Receptor Interactions by Homology Molecular Modeling and Validation Using Chimeric Peptide Ligands,”J. Med. Chem., Mar. 20, 2004, vol. 47, No. 9, pp. 2194-2207.
Wilczynski, A. et al., “Structural Characterization and Pharmacology of a Potent (Cys101-Cys119, Cys110-Cys117) Bicyclic Agouti-Related Protein (AGRP) Melanocortin Receptor Antagonist,”J. Med. Chem., Oct. 2004, vol. 47, pp. 5662-5673.
Wilczynski, A. et al., “Structure-Activity Relationships of the Unique and Potent Agouti-Related Protein (AGRP)-Melanocortin Chimeric Tyr-c[β-Asp-His-DPhe-Arg-Trp-Asn-Ala-Phe-Dpr]-Tyr-NH Peptide Template,”J. Med. Chem., Mar. 26, 2005, vol. 48, No. 8, pp. 3060-3075.
Yang, Y. et al., “Molecular Determinants of Ligand Binding to the Human Melanocortin-4 Receptor,”Biochemistry, Oct. 2000, vol. 39, pp. 14900-14911.
Yaswen, L. et al., “Obesity in the mouse model of pro-opiomelanocortin deficiency responds to peripheral melanocortin,”Nature Medicine, Sep. 1999, vol. 5, No. 9, pp. 1066-1070.
Yeo, G. et al., “A frameshift mutation inMC4Rassociated with dominantly inherited human obesity,”Nature Genetics, Oct. 1998, vol. 20, pp. 111-112.
Yeo, G. et al., “Mutations in the human melanocortin-4 receptor gene associated with severe familial obesity disrupts receptor function through multiple molecular mechanisms,”Human Molecular Genetics, 2003, vol. 12, No. 5, pp. 561-574.

Affiliated with

Also associated with

Rating

Biological active ligands of melanocortin receptors does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Biological active ligands of melanocortin receptors, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Biological active ligands of melanocortin receptors will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-4275478