Publications

Ericson M, Larson C, Freeman K, Nicke L, Geyer A, Haskell-Luevano C. Incorporation of Indoylated Phenylalanine Yields a Sub-Micromolar Selective Melanocortin-4 Receptor Antagonist Tetrapeptide. ACS Omega, 2022, 7, 27656-27663 (doi: 10.1021/acsomega.2c03307).

1. Ericson MD, Doering SR, Larson CM, Freeman KT, LaVoi TM, Donow HM, Santos RG, Cho RH, Koerperich ZM, Giulianotti MA, Pinilla C, Houghten RA, Haskell-Luevano C. Functional Mixture-Based Positional Scan Identifies a Library of Antagonist Tetrapeptide Sequences (LAtTeS) with Nanomolar Potency for the Melanocortin-4 Receptor and Equipotent with the Endogenous AGRP(86-132) Antagonist. J. Med. Chem., 2021, 64, 14860-14875 (doi: 10.1021/acs.jmedchem.1c01417). 

2. Doering SR, Freeman K, Debevec G, Geer P, Santos RG, Lavoi TM, Giulianotti MA, Pinilla C, Appel JR, Houghten RA, Ericson MD, Haskell-Luevano C. Discovery of nanomolar melanocortin-3 receptor (MC3R) selective small molecule pyrrolidine bis-cyclic guanidine agonist compounds via a high throughput “unbiased” screening campaign. J. Med. Chem., 2021, 64, 5577-5592 (doi: 10.1021/acs.jmedchem.0c02041).

3. Yeo GSH, Moro Chao DH, Siegert AM, Koerperich ZM, Ericson MD, Simonds SE, Larson CM, Luquet S, Clarke I, Sharma S, Clément K, Cowley MA, Haskell-Luevano C, Van Der Ploeg L, Adan RAH. The melanocortin pathway and energy homeostasis: From discovery to obesity therapy. Mol. Metab., 2021, 48, 101206 (doi: 10.1016/j.molmet.2021.101206). 

4. Koikov L, Starner RJ, Swope VB, Upadhyay P, Hashimoto Y, Freeman KT, Knittel JJ, Haskell-Luevano C, Abdel-Malek ZA. Development of hMC1R selective small agonists for sunless tanning and prevention of genotoxicity of UV in melanocytes. J. Invest. Dermatol., 2021, 141, 1819-1829 (doi: 10.1016/j.jid.2020.11.034). 

5. Ericson MD, Haslach EM, Schnell SM, Freeman KT, Xiang ZM, Portillo FP, Speth R, Litherland SA, Haskell-Luevano C. Discovery of molecular interactions of the human melanocortin-4 receptor (hMC4R) Asp189 (D189) amino acid with the endogenous G-protein-coupled receptor (GPCR) antagonist agouti-related protein (AGRP) provides insights to AGRP's inverse agonist pharmacology at the hMC4R. ACS Chem. Neurosci., 2021, 12, 542-556 (doi: 10.1021/acschemneuro.0c00755).

6. Ericson MD, Shaikh R, Larson CM, Freeman KT, Haskell-Luevano C. Multiresidue tetrapeptide substitutions yield a 140-fold selective melanocortin-3 over melanocortin-4 receptor agonist. ACS Med. Chem. Lett., 2021, 12, 115-120 (doi: 10.1021/acsmedchemlett.0c00561). 

1. Ericson MD, Freeman KT, Haskell-Luevano C. Peptoid NPhe4 in AGRP-based c[Pro1-Arg2-Phe3-Phe4-Xxx5-Ala6-Phe7-DPro8] scaffolds maintain mouse MC4R antagonist potency. ACS Med. Chem. Lett., 2020, 11, 1942-1948 (doi: 10.1021/acsmedchemlett.9b00641). 

2. Adank DN, Lunzer MM, Ericson MD, Koeperich ZM, Wilber SL, Fleming KA, Haskell-Luevano C. Comparative intracerebroventricular and intrathecal administration of a nanomolar macrocyclic melanocortin receptor agonist MDE6-5-2c (c[Pro-His-DPhe-Arg-Trp-Dap-Ala-DPro]) decreases food intake in mice. ACS Chem. Neurosci., 2020, 11, 3051-3063 (doi: 10.1021/acschemneuro.0c00409).

3. Winget MD, Ericson MD, Freeman KT, Haskell-Luevano C. Single nucleotide polymorphisms in the melanocortin His-Phe-Arg-Trp sequences decrease tetrapeptide potency and efficacy. ACS Med. Chem. Lett., 2020, 11, 272-277 (doi: 10.1021/acsmedchemlett.9b00198). 

4. Koerperich ZM, Ericson MD, Freeman KT, Speth RC, Pogozheva ID, Mosberg HI, Haskell-Luevano C. Incorporation of agouti-related protein (AgRP) human single nucleotide polymorphisms (SNPs) in the AGRP-derived macrocyclic scaffold c[Pro-Arg-Phe-Phe-Asn-Ala-Phe-dPro] decreases melanocortin-4 receptor antagonist potency and results in the discovery of melanocortin-5 receptor antagonists. J. Med. Chem., 2020, 63, 2194-2208 (doi: 10.1021/acs.jmedchem.9b00860). 

1. Schlasner KN, Ericson MD, Doering SR, Freeman KT, Weinrich M, Haskell-Luevano C. Structure⁻activity relationships of the tetrapeptide Ac-His-Arg-(pI)DPhe-Tic-NH2 at the mouse melanocortin receptors: Modification at the (pI)DPhe position leads to mMC3R versus mMC4R selective ligands. Molecules, 2019, 24 (doi: 10.3390/molecules24081463).

2. Fleming KA, Freeman KT, Powers MD, Santos RG, Debevec G, Giulianotti MA, Houghten RA, Doering SR, Pinilla C, Haskell-Luevano C. Discovery of polypharmacological melanocortin-3 and -4 receptor probes and identification of a 100-fold selective nM MC3R agonist versus a μM MC4R partial agonist. J. Med. Chem., 2019, 62, 2738-2749 (doi: 10.1021/acs.jmedchem.9b00053).

3. Lensing CJ, Freeman KT, Schnell SM, Speth RC, Zarth AT, Haskell-Luevano C. Developing a biased unmatched bivalent ligand (BUmBL) design strategy to target the GPCR homodimer allosteric signaling (cAMP over β-Arrestin 2 recruitment) within the melanocortin receptors. J. Med. Chem., 2019, 62, 144-158 (doi: 10.1021/acs.jmedchem.8b00238). 

2018

1. Ericson MD, Koerperich ZM, Freeman KT, Fleming KA, Haskell-Luevano C. Arg-Phe-Phe D-Amino acid stereochemistry scan in the macrocyclic agouti-related protein antagonist scaffold c[Pro-Arg-Phe-Phe-Xxx-Ala-Phe-DPro] results in unanticipated melanocortin-1 receptor agonist profiles. ACS Chem. Neurosci., 2018, 9, 3015-3023 (doi: 10.1021/acschemneuro.8b00218).

2. Todorovic A, Lensing CJ, Holder JR, Scott JW, Sorensen NB, Haskell-Luevano C. Discovery of melanocortin ligands via a double simultaneous substitution strategy based on the Ac-His-DPhe-Arg-Trp-NH2 template. ACS Chem. Neurosci., 2018, 9, 2753-2766 (doi: 10.1021/acschemneuro.8b00181).

3. Fleming KA, Freeman KT, Ericson MD, Haskell-Luevano C. Synergistic multiresidue substitutions of a macrocyclic c[Pro-Arg-Phe-Phe-Asn-Ala-Phe-dPro] agouti-related protein (AGRP) scaffold yield potent and >600-fold MC4R versus MC3R selective melanocortin receptor antagonists. J. Med. Chem., 2018, 61, 7729-7740 (doi: 10.1021/acs.jmedchem.8b00684).

4. Ericson MD, Haskell-Luevano C. A review of single-nucleotide polymorphisms in orexigenic neuropeptides targeting G protein-coupled receptors. ACS Chem. Neurosci., 2018, 9, 1235-1246 (doi: 10.1021/acschemneuro.8b00151).

5. Tala SR, Singh A, Lensing CJ, Schnell SM, Freeman KT, Rocca JR, Haskell-Luevano C. 1,2,3-Triazole rings as a disulfide bond mimetic in chimeric AGRP-melanocortin peptides: Design, synthesis, and functional characterization. ACS Chem. Neurosci., 2018, 9, 1001-1013 (doi: 10.1021/acschemneuro.7b00422).

6. Fleming KA, Ericson MD, Freeman KT, Adank DN, Lunzer MM, Wilber SL, Haskell-Luevano C. Structure-activity relationship studies of a macrocyclic AGRP-mimetic scaffold c[Pro-Arg-Phe-Phe-Asn-Ala-Phe-DPro] yield potent and selective melanocortin-4 receptor antagonists and melanocortin-5 receptor inverse agonists that increase food intake in mice. ACS Chem. Neurosci., 2018, 9, 1141-1151 (doi: 10.1021/acschemneuro.7b00495).

7. Ericson MD, Singh A, Tala SR, Haslach EM, Dirain MLS, Schaub JW, Flores V, Eick N, Lensing CJ, Freeman KT, Smeester BA, Adank DN, Wilber SL, Speth R, Haskell-Luevano C. Human β-defensin 1 and β-defensin 3 (mouse ortholog mBD14) function as full endogenous agonists at select melanocortin receptors. J. Med. Chem., 2018, 61, 3738-3744 (doi: 10.1021/acs.jmedchem.8b00251).

8. Haskell-Luevano C, Georg GI, Wang S, Meanwell N. Allosteric modulators of drug targets special issue. J. Med. Chem., 2018, 61, 1381 (doi: 10.1021/acs.jmedchem.8b00171).

9. Adank DN, Lunzer MM, Lensing CJ, Wilber SL, Gancarz AM, Haskell-Luevano C. Comparative in vivo investigation of intrathecal and intracerebroventricular administration with melanocortin ligands MTII and AGRP into mice. ACS Chem. Neurosci., 2018, 9, 320-327 (doi: 10.1021/acschemneuro.7b00330).

2017

10. Ericson MD, Freeman KT, Schnell SM, Fleming KA, Haskell-Luevano C. Structure-activity relationship studies on a macrocyclic agouti-related protein (AGRP) scaffold reveal agouti signaling protein (ASP) residue substitutions maintain melanocortin-4 receptor antagonist potency and result in inverse agonist pharmacology at the melanocortin-5 receptor. J. Med. Chem., 2017, 60, 8103-8114 (doi: 10.1021/acs.jmedchem.7b00856).

11. Ericson MD, Lensing CJ, Fleming KA, Schlasner KN, Doering SR, Haskell-Luevano C. Bench-top to clinical therapies: A review of melanocortin ligands from 1954 to 2016. Biochim. Biophys. Acta Mol. Basis. Dis., 2017, 1863, 2414-2435 (doi: 10.1016/j.bbadis.2017.03.020). 

12. Lensing CJ, Adank DN, Wilber SL, Freeman KT, Schnell SM, Speth RC, Zarth AT, Haskell-Luevano C. A direct in vivo comparison of the melanocortin monovalent agonist Ac-His-DPhe-Arg-Trp-NH2 versus the bivalent agonist Ac-His-DPhe-Arg-Trp-PEDG20-His-DPhe-Arg-Trp-NH2: A bivalent advantage. ACS Chem. Neurosci., 2017, 8, 1262-1278 (doi: 10.1021/acschemneuro.6b00399).

13. Doering SR, Freeman KT, Schnell SM, Haslach EM, Dirain M, Debevec G, Geer P, Santos RG, Giulianotti MA, Pinilla C, Appel JR, Speth RC, Houghten RA, Haskell-Luevano C. Discovery of mixed pharmacology melanocortin-3 agonists and melanocortin-4 receptor tetrapeptide antagonist compounds (TACOs) based on the sequence Ac-Xaa1-Arg-(pI)DPhe-Xaa4-NH2. J. Med. Chem., 2017, 60, 4342-4357 (doi: 10.1021/acs.jmedchem.7b00301).

14. Ericson MD, Freeman KT, Schnell SM, Haskell-Luevano C. A macrocyclic agouti-related protein/[Nle4,DPhe7]α-melanocyte stimulating hormone chimeric scaffold produces subnanomolar melanocortin receptor ligands. J. Med. Chem., 2017, 60, 805-813 (doi: 10.1021/acs.jmedchem.6b01707).

2016

15. Lensing CJ, Adank DN, Doering SR, Wilber SL, Andreasen A, Schaub JW, Xiang Z, Haskell-Luevano C. Ac-Trp-DPhe(p-I)-Arg-Trp-NH2, a 250-fold selective melanocortin-4 receptor (MC4R) antagonist over the melanocortin-3 receptor (MC3R), affects energy homeostasis in male and female mice differently. ACS Chem. Neurosci., 2016, 7, 1283-1291 (doi: 10.1021/acschemneuro.6b00156).

16. Todorovic A, Ericson MD, Palusak RD, Sorensen NB, Wood MS, Xiang Z, Haskell-Luevano C. Comparative functional alanine positional scanning of the α-melanocyte stimulating hormone and NDP-melanocyte stimulating hormone demonstrates differential structure-activity relationships at the mouse melanocortin receptors. ACS Chem. Neurosci., 2016, 7, 984-994 (doi: 10.1021/acschemneuro.6b00098).

17. Lensing CJ, Freeman KT, Schnell SM, Adank DN, Speth RC, Haskell-Luevano C. An in vitro and in vivo investigation of bivalent ligands that display preferential binding and functional activity for different melanocortin receptor homodimers. J. Med. Chem., 2016, 59, 3112-3128 (doi: 10.1021/acs.jmedchem.5b01894).

18. Singh A, Kast J, Dirain ML, Huang H, Haskell-Luevano C. Synthesis and structure-activity relationships of substituted urea derivatives on mouse melanocortin receptors. ACS Chem. Neurosci., 2016, 7, 196-205 (doi: 10.1021/acschemneuro.5b00273). 

2015

19. Tala SR, Schnell SM, Haskell-Luevano C. Microwave-assisted solid-phase synthesis of side-chain to side-chain lactam-bridge cyclic peptides. Bioorg. Med. Chem. Lett., 2015, 25, 5708-5711 (doi: 10.1016/j.bmcl.2015.10.095).

20. Ericson MD, Schnell SM, Freeman KT, Haskell-Luevano C. A fragment of the Escherichia coli ClpB heat-shock protein is a micromolar melanocortin 1 receptor agonist. Bioorg. Med. Chem. Lett., 2015, 25, 5306-5308 (doi: 10.1016/j.bmcl.2015.09.046).

21. Garrigan E, Belkin NS, Seydel F, Han Z, Carter J, McDuffie M, Morel L, Peck AB, Clare-Salzler MJ, Atkinson M, Wasserfall C, Davoodi-Semiromi A, Shi JD, Haskell-Luevano C, Yang LJ, Alexander JJ, Cdebaca A, Piliant T, Riggs C, Amick M, Litherland SA. Csf2 and Ptgs2 epigenetic dysregulation in diabetes-prone bicongenic B6.NODC11bxC1tb mice. Genet. Epigenet., 2015, 7, 5-17 (doi: 10.4137/GEG.S29696).

22. Ericson MD, Wilczynski A, Sorensen NB, Xiang Z, Haskell-Luevano C. Discovery of a β-hairpin octapeptide, c[Pro-Arg-Phe-Phe-Dap-Ala-Phe-DPro], mimetic of agouti-related protein(87-132) [AGRP(87-132)] with equipotent mouse melanocortin-4 receptor (mMC4R) antagonist pharmacology. J. Med. Chem., 2015, 58, 4638-4647 (doi: 10.1021/acs.jmedchem.5b00184).

23. Singh A, Tala SR, Flores V, Freeman K, Haskell-Luevano C. Synthesis and pharmacology of α/β(3)-peptides based on the melanocortin agonist Ac-His-DPhe-Arg-Trp-NH2 sequence. ACS Med. Chem. Lett., 2015, 6, 568-572 (doi: 10.1021/acsmedchemlett.5b00053).

24. Doering SR, Todorovic A, Haskell-Luevano C. Melanocortin antagonist tetrapeptides with minimal agonist activity at the mouse melanocortin-3 receptor. ACS Med. Chem. Lett., 2015, 6, 123-127 (doi: 10.1021/ml500340z). 

2014

25. Testa C, Scrima M, Grimaldi M, D'Ursi AM, Dirain ML, Lubin-Germain N, Singh A, Haskell-Luevano C, Chorev M, Rovero P, Papini AM. 1,4-Disubstituted-[1,2,3]triazolyl-containing analogues of MT-II: Design, synthesis, conformational analysis, and biological activity. J. Med. Chem., 2014, 57, 9424-9434 (doi: 10.1021/jm501027w).

26. Singh A, Dirain ML, Wilczynski A, Chen C, Gosnell BA, Levine AS, Edison AS, Haskell-Luevano C. Synthesis, biophysical, and pharmacological evaluation of the melanocortin agonist AST3-88: Modifications of peptide backbone at Trp 7 position lead to a potent, selective, and stable ligand of the melanocortin 4 receptor (MC4R). ACS Chem. Neurosci., 2014, 5, 1020-1031 (doi: 10.1021/cn5000953).

27. Haslach EM, Huang H, Dirain M, Debevec G, Geer P, Santos RG, Giulianotti MA, Pinilla C, Appel JR, Doering SR, Walters MA, Houghten RA, Haskell-Luevano C. Identification of tetrapeptides from a mixture based positional scanning library that can restore nM full agonist function of the L106P, I69T, I102S, A219V, C271Y, and C271R human melanocortin-4 polymorphic receptors (hMC4Rs). J. Med. Chem., 2014, 57, 4615-4628 (doi: 10.1021/jm500064t).

2013

28. Singh A, Dirain M, Witek R, Rocca JR, Edison AS, Haskell-Luevano C. Structure-activity relationships of peptides incorporating a bioactive reverse-turn heterocycle at the melanocortin receptors: Identification of a 5800-fold mouse melanocortin-3 receptor (mMC3R) selective antagonist/partial agonist versus the mouse melanocortin-4 receptor (mMC4R). J. Med. Chem., 2013, 56, 2747-2763 (doi: 10.1021/jm301253y).

2011

29. Irani BG, Xiang Z, Yarandi HN, Holder JR, Moore MC, Bauzo RM, Proneth B, Shaw AM, Millard WJ, Chambers JB, Benoit SC, Clegg DJ, Haskell-Luevano C. Implication of the melanocortin-3 receptor in the regulation of food intake. Eur. J. Pharmacol., 2011, 660, 80-87 (doi: 10.1016/j.ejphar.2010.10.101).

30. Hinkle PM, Serasinghe MN, Jakabowski A, Sebag JA, Wilson KR, Haskell-Luevano C. Use of chimeric melanocortin-2 and -4 receptors to identify regions responsible for ligand specificity and dependence on melanocortin 2 receptor accessory protein. Eur. J. Pharmacol., 2011, 660, 94-102 (doi: 10.1016/j.ejphar.2010.10.113). 

31. Singh A, Wilczynski A, Holder JR, Witek RM, Dirain ML, Xiang Z, Edison AS, Haskell-Luevano C. Incorporation of a bioactive reverse-turn heterocycle into a peptide template using solid-phase synthesis to probe melanocortin receptor selectivity and ligand conformations by 2D 1H NMR. J. Med. Chem., 2011, 54, 1379-1390 (doi: 10.1021/jm101425m).

2010

32. Joseph CG, Yao H, Scott JW, Sorensen NB, Marnane RN, Mountjoy KG, Haskell-Luevano C. γ₂-Melanocyte stimulation hormone (γ₂-MSH) truncation studies results in the cautionary note that γ₂-MSH is not selective for the mouse MC3R over the mouse MC5R. Peptides, 2010, 31, 2304-2313 (doi: 10.1016/j.peptides.2010.08.025).

33. Rowland NE, Schaub JW, Robertson KL, Andreasen A, Haskell-Luevano C. Effect of MTII on food intake and brain c-Fos in melanocortin-3, melanocortin-4, and double MC3 and MC4 receptor knockout mice. Peptides, 2010, 31, 2314-2317 (doi: 10.1016/j.peptides.2010.08.016).

34. Rowland NE, Fakhar KJ, Robertson KL, Haskell-Luevano C. Effect of serotonergic anorectics on food intake and induction of Fos in brain of mice with disruption of melanocortin 3 and/or 4 receptors. Pharmacol. Biochem. Behav., 2010, 97, 107-111 (doi: 10.1016/j.pbb.2010.03.008).

35. Xiang Z, Proneth B, Dirain ML, Litherland SA, Haskell-Luevano C. Pharmacological characterization of 30 human melanocortin-4 receptor polymorphisms with the endogenous proopiomelanocortin-derived agonists, synthetic agonists, and the endogenous agouti-related protein antagonist. Biochemistry, 2010, 49, 4583-4600 (doi: 10.1021/bi100068u).

36. Atalayer D, Robertson KL, Haskell-Luevano C, Andreasen A, Rowland NE. Food demand and meal size in mice with single or combined disruption of melanocortin type 3 and 4 receptors. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2010, 298, R1667-1674 (doi: 10.1152/ajpregu.00562.2009).

37. Ovadia O, Linde Y, Haskell-Luevano C, Dirain ML, Sheynis T, Jelinek R, Gilon C, Hoffman A. The effect of backbone cyclization on PK/PD properties of bioactive peptide-peptoid hybrids: The melanocortin agonist paradigm. Bioorg. Med. Chem., 2010, 18, 580-589 (doi: 10.1016/j.bmc.2009.12.010).

38. Singh A, Haslach EM, Haskell-Luevano C. Structure-activity relationships (SAR) of melanocortin and agouti-related (AGRP) peptides. Adv. Exp. Med. Biol., 2010, 681, 1-18 (doi: 10.1007/978-1-4419-6354-3_1).

39. Schaub JW, Bruce EB, Haskell-Luevano C. Drugs, exercise, and the melanocortin-4 receptor - different means, same ends: Treating obesity. Adv. Exp. Med. Biol., 2010, 681, 49-60 (doi: 10.1007/978-1-4419-6354-3_4).

2009

40. Abdel-Malek ZA, Ruwe A, Kavanagh-Starner R, Kadekaro AL, Swope V, Haskell-Luevano C, Koikov L, Knittel JJ. α-MSH tripeptide analogs activate the melanocortin 1 receptor and reduce UV-induced DNA damage in human melanocytes. Pigment Cell Melanoma Res., 2009, 22, 635-644 (doi: 10.1111/j.1755-148X.2009.00598.x).

41. Ruwe AR, Koikov L, Abdel-Malek Z, Haskell-Luevano C, Dirain ML, Portillo F, Xiang Z, Wortman M, Knittel JJ. Semi-rigid tripeptide agonists of melanocortin receptors. Bioorg. Med. Chem. Lett., 2009, 19, 5176-5181 (doi: 10.1016/j.bmcl.2009.07.025).

42. Santoro N, Cirillo G, Xiang Z, Tanas R, Greggio N, Morino G, Iughetti L, Vottero A, Salvatoni A, Di Pietro M, Balsamo A, Crinò A, Grandone A, Haskell-Luevano C, Perrone L, del Giudice EM. Prevalence of pathogenetic MC4R mutations in Italian children with early onset obesity, tall stature and familial history of obesity. BMC Med. Genet., 2009, 10, 25 (doi: 10.1186/1471-2350-10-25).

43. Haskell-Luevano C, Schaub JW, Andreasen A, Haskell KR, Moore MC, Koerper LM, Rouzaud F, Baker HV, Millard WJ, Walter G, Litherland SA, Xiang Z. Voluntary exercise prevents the obese and diabetic metabolic syndrome of the melanocortin-4 receptor knockout mouse. FASEB J., 2009, 23, 642-655 (doi: 10.1096/fj.08-109686).

44. Haslach EM, Schaub JW, Haskell-Luevano C. β-Turn secondary structure and melanocortin ligands. Bioorg. Med. Chem., 2009, 17, 952-958 (doi: 10.1016/j.bmc.2008.02.090).

45. Haskell-Luevano C, Xiang Z, Wilczynski AM, Haskell KR, Andreasen AM, Litherland SA, Millard WJ, Pogozheva ID, Mosberg HI, Sorenson NB. Discovery of a ligand that compensates for decreased endogenous agonist potency of melanocortin-4 receptor polymorphisms identified in obese humans. Adv. Exp. Med. Biol., 2009, 611, 509-10 (doi: 10.1007/978-0-387-73657-0_221).

46. Wilson KR, Proneth B, Luesch H, Litherland SA, Haskell-Luevano C. Construction and characterization of melanocortin-2 and -4 receptor chimeras. Adv. Exp. Med. Biol., 2009, 611, 301-302 (doi: 10.1007/978-0-387-73657-0_135).

47. Proneth B, Portillo FP, Haskell-Luevano C. A combination of ligand SAR and receptor site-directed mutagenesis reveals requirements for antagonist activity at the melanocortin-3 receptor. Adv. Exp. Med. Biol., 2009, 611, 319-320 (doi: 10.1007/978-0-387-73657-0_142).

2008

48. Proneth B, Pogozheva ID, Portillo FP, Mosberg HI, Haskell-Luevano C. Melanocortin tetrapeptide Ac-His-DPhe-Arg-Trp-NH2 modified at the para position of the benzyl side chain (DPhe): importance for mouse melanocortin-3 receptor agonist versus antagonist activity. J. Med. Chem., 2008, 51, 5585-5593 (doi: 10.1021/jm800291b).

49. Joseph CG, Wilson KR, Wood MS, Sorenson NB, Phan DV, Xiang Z, Witek RM, Haskell-Luevano C. The 1,4-benzodiazepine-2,5-dione small molecule template results in melanocortin receptor agonists with nanomolar potencies. J. Med. Chem., 2008, 51, 1423-1431 (doi: 10.1021/jm701303z).

50. Hess S, Linde Y, Ovadia O, Safrai E, Shalev DE, Swed A, Halbfinger E, Lapidot T, Winkler I, Gabinet Y, Faier A, Yarden D, Xiang Z, Portillo FP, Haskell-Luevano C, Gilon C, Hoffman A. Backbone cyclic peptidomimetic melanocortin-4 receptor agonist as a novel orally administrated drug lead for treating obesity. J. Med. Chem., 2008, 51, 1026-1034 (doi: 10.1021/jm701093y).

51. Linde Y, Ovadia O, Safrai E, Xiang Z, Portillo FP, Shalev DE, Haskell-Luevano C, Hoffman A, Gilon C. Structure-activity relationship and metabolic stability studies of backbone cyclization and N-methylation of melanocortin peptides. Biopolymers, 2008, 90, 671-682 (doi: 10.1002/bip.21057).

2007

52. Katritzky AR, Khashab NM, Yoshioka M, Haase DN, Wilson KR, Johnson JV, Chung A, Haskell-Luevano C. Microwave-assisted solid-phase peptide synthesis utilizing N-Fmoc-protected (α-aminoacyl)benzotriazoles. Chem. Biol. Drug Des., 2007, 70, 465-468 (doi: 10.1111/j.1747-0285.2007.00584.x).

53. Xiang Z, Pogozheva ID, Sorenson NB, Wilczynski AM, Holder JR, Litherland SA, Millard WJ, Mosberg HI, Haskell-Luevano C. Peptide and small molecules rescue the functional activity and agonist potency of dysfunctional human melanocortin-4 receptor polymorphisms. Biochemistry, 2007, 46, 8273-8287 (doi: 10.1021/bi7007382). 

54. Todorovic A, Joseph CG, Sorensen NB, Wood MS, Haskell-Luevano C. Structure-activity relationships of melanocortin agonists containing the benzimidazole scaffold. Chem. Biol. Drug Des., 2007, 69, 338-349 (doi: 10.1111/j.1747-0285.2007.00511.x).

2006

55. Vaughan CH, Haskell-Luevano C, Andreasen A, Rowland NE. Effects of oral preload, CCK or bombesin administration on short term food intake of melanocortin 4-receptor knockout (MC4RKO) mice. Peptides, 2006, 27, 3226-3233 (doi: 10.1016/j.peptides.2006.08.002).

56. Chen M, Georgeson KE, Harmon CM, Haskell-Luevano C, Yang Y. Functional characterization of the modified melanocortin peptides responsible for ligand selectivity at the human melanocortin receptors. Peptides, 2006, 27, 2836-2845 (doi: 10.1016/j.peptides.2006.04.012).

57. Vaughan C, Moore M, Haskell-Luevano C, Rowland NE. Food motivated behavior of melanocortin-4 receptor knockout mice under a progressive ratio schedule. Peptides, 2006, 27, 2829-2835 (doi: 10.1016/j.peptides.2006.07.008). 

58. Abdel-Malek ZA, Kadekaro AL, Kavanagh RJ, Todorovic A, Koikov LN, McNulty JC, Jackson PJ, Millhauser GL, Schwemberger S, Babcock G, Haskell-Luevano C, Knittel JJ. Melanoma prevention strategy based on using tetrapeptide α-MSH analogs that protect human melanocytes from UV-induced DNA damage and cytotoxicity. FASEB J., 2006, 20, 1561-1563 (doi: 10.1096/fj.05-5655fje). 

59. Xiang Z, Litherland SA, Sorensen NB, Proneth B, Wood MS, Shaw AM, Millard WJ, Haskell-Luevano C. Pharmacological characterization of 40 human melanocortin-4 receptor polymorphisms with the endogenous proopiomelanocortin-derived agonists and the agouti-related protein (AGRP) antagonist. Biochemistry, 2006, 45, 7277-7288 (doi: 10.1021/bi0600300).

60. Wilson KR, Todorovic A, Proneth B, Haskell-Luevano C. Overview of endogenous and synthetic melanocortin peptides. Cell Mol. Biol., 2006, 52, 3-20. 

61. Boeglin D, Xiang Z, Sorenson NB, Wood MS, Haskell-Luevano C, Lubell WD. Aza-scanning of the potent melanocortin receptor agonist Ac-His-D-Phe-Arg-Trp-NH2. Chem. Biol. Drug Des., 2006, 67, 275-283 (doi: 10.1111/j.1747-0285.2006.00378.x).

62. Proneth B, Xiang Z, Pogozheva ID, Litherland SA, Gorbatyuk OS, Shaw AM, Millard WJ, Mosberg HI, Haskell-Luevano C. Molecular mechanism of the constitutive activation of the L250Q human melanocortin-4 receptor polymorphism. Chem. Biol. Drug Des., 2006, 67, 215-229 (doi: 10.1111/j.1747-0285.2006.00362.x).

63. Murray JF, Hahn JD, Kennedy AR, Small CJ, Bloom SR, Haskell-Luevano C, Coen CW, Wilson CA. Evidence for a stimulatory action of melanin-concentrating hormone on luteinising hormone release involving MCH1 and melanocortin-5 receptors. J. Neuroendocrinol., 2006, 18, 157-167 (doi: 10.1111/j.1365-2826.2005.01397.x).

64. Haskell-Luevano C. Physiology and chemistry of the melanocortin pathway. Peptides, 2006, 27, 257-258 (doi: 10.1016/j.peptides.2005.05.008). 

2005

65. Joseph CG, Sorensen NB, Wood MS, Xiang Z, Moore MC, Haskell-Luevano C. Modified melanocortin tetrapeptide Ac-His-DPhe-Arg-Trp-NH2 at the arginine side chain with ureas and thioureas. J. Pept. Res., 2005, 66, 297-307 (doi: 10.1111/j.1399-3011.2005.00303.x).

66. Todorovic A, Haskell-Luevano C. A review of melanocortin receptor small molecule ligands. Peptides, 2005, 26, 2026-2036 (doi: 10.1016/j.peptides.2004.11.024).

67. Irani BG, Haskell-Luevano C. Feeding effects of melanocortin ligands - a historical perspective. Peptides, 2005, 26, 1788-1799 (doi: 10.1016/j.peptides.2004.11.038).

68. Eylam S, Moore M, Haskell-Luevano C, Spector AC. Melanocortin-4 receptor-null mice display normal affective licking responses to prototypical taste stimuli in a brief-access test. Peptides, 2005, 26, 1712-1719 (doi: 10.1016/j.peptides.2004.11.023).

69. Shaw AM, Irani BG, Moore MC, Haskell-Luevano C, Millard WJ. Ghrelin-induced food intake and growth hormone secretion are altered in melanocortin 3 and 4 receptor knockout mice. Peptides, 2005, 26, 1720-1727 (doi: 10.1016/j.peptides.2004.12.026). 

70. Wilczynski AM, Joseph CG, Haskell-Luevano C. Current trends in the structure-activity relationship studies of the endogenous agouti-related protein (AGRP) melanocortin receptor antagonist. Med. Res. Rev., 2005, 25, 545-556 (doi: 10.1002/med.20037). 

71. Todorovic A, Holder JR, Bauzo RM, Scott JW, Kavanagh R, Abdel-Malek Z, Haskell-Luevano C. N-terminal fatty acylated His-DPhe-Arg-Trp-NH2 tetrapeptides: Influence of fatty acid chain length on potency and selectivity at the mouse melanocortin receptors and human melanocytes. J. Med. Chem., 2005, 48, 3328-3336 (doi: 10.1021/jm0490843). 

72. Wilczynski A, Wilson KR, Scott JW, Edison AS, Haskell-Luevano C. 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-NH2 peptide template. J. Med. Chem., 2005, 48, 3060-3075 (doi: 10.1021/jm049010r). 

73. Vaughan CH, Moore MC, Haskell-Luevano C, Rowland NE. Meal patterns and foraging in melanocortin receptor knockout mice. Physiol. Behav., 2005, 84, 129-133 (doi: 10.1016/j.physbeh.2004.10.016). 

74. Irani BG, Xiang Z, Moore MC, Mandel RJ, Haskell-Luevano C. Voluntary exercise delays monogenetic obesity and overcomes reproductive dysfunction of the melanocortin-4 receptor knockout mouse. Biochem. Biophys. Res. Commun., 2005, 326, 638-644 (doi: 10.1016/j.bbrc.2004.11.084). 

75. Sharov AA, Fessing M, Atoyan R, Sharova TY, Haskell-Luevano C, Weiner L, Funa K, Brissette JL, Gilchrest BA, Botchkarev VA. Bone morphogenetic protein (BMP) signaling controls hair pigmentation by means of cross-talk with the melanocortin receptor-1 pathway. Proc. Natl. Acad. Sci. USA, 2005, 102, 93-98 (doi: 10.1073/pnas.0408455102). 

2004

76. Joseph CG, Wang XS, Scott JW, Bauzo RM, Xiang Z, Richards NG, Haskell-Luevano C. Stereochemical studies of the monocyclic agouti-related protein (103-122) Arg-Phe-Phe residues: Conversion of a melanocortin-4 receptor antagonist into an agonist and results in the discovery of a potent and selective melanocortin-1 agonist. J. Med. Chem., 2004, 47, 6702-6710 (doi: 10.1021/jm0492756). 

77. Wilczynski A, Wang XS, Bauzo RM, Xiang Z, Shaw AM, Millard WJ, Richards NG, Edison AS, Haskell-Luevano C. Structural characterization and pharmacology of a potent (Cys101-Cys119, Cys110-Cys117) bicyclic agouti-related protein (AGRP) melanocortin receptor antagonist. J. Med. Chem., 2004, 47, 5662-5673 (doi: 10.1021/jm049620r). 

78. Haskell-Luevano C, Todorovic A, Gridley K, Sorenson N, Irani B, Xiang Z. The melanocortin pathway: Effects of voluntary exercise on the melanocortin-4 receptor knockout mice and ACTH(1-24) ligand structure activity relationships at the melanocortin-2 receptor. Endocr. Res., 2004, 30, 591-597 (doi: 10.1081/erc-200043759). 

79. Holder JR, Haskell-Luevano C. Melanocortin ligands: 30 Years of structure-activity relationship (SAR) studies. Med. Res. Rev., 2004, 24, 325-356 (doi: 10.1002/med.10064). 

80. Wilczynski A, Wang XS, Joseph CG, Xiang Z, Bauzo RM, Scott JW, Sorensen NB, Shaw AM, Millard WJ, Richards NG, Haskell-Luevano C. 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., 2004, 47, 2194-2207 (doi: 10.1021/jm0303608). 

81. Han G, Haskell-Luevano C, Kendall L, Bonner G, Hadley ME, Cone RD, Hruby VJ. De novo design, synthesis, and pharmacology of α-melanocyte stimulating hormone analogues derived from somatostatin by a hybrid approach. J. Med. Chem., 2004, 47, 1514-1526 (doi: 10.1021/jm030452x). 

82. Todorovic A, Holder JR, Scott JW, Haskell-Luevano C. Synthesis and activity of the melanocortin Xaa-DPhe-Arg-Trp-NH2 tetrapeptides with amide bond modifications. J. Pept. Res., 2004, 63, 270-278 (doi: 10.1111/j.1399-3011.2004.00137.x).

83. Irani BG, Holder JR, Todorovic A, Wilczynski AM, Joseph CG, Wilson KR, Haskell-Luevano C. Progress in the development of melanocortin receptor selective ligands. Curr. Pharm. Des., 2004, 10, 3443-3479 (doi: 10.2174/1381612043382891). 

2003

84. Holder JR, Bauzo RM, Xiang Z, Scott J, Haskell-Luevano C. Design and pharmacology of peptoids and peptide-peptoid hybrids based on the melanocortin agonists core tetrapeptide sequence. Bioorg. Med. Chem. Lett., 2003, 13, 4505-4509 (doi: 10.1016/j.bmcl.2003.08.078).

85. Joseph CG, Wilczynski A, Holder JR, Xiang Z, Bauzo RM, Scott JW, Haskell-Luevano C. Chimeric NDP-MSH and MTII melanocortin peptides with agouti-related protein (AGRP) Arg-Phe-Phe amino acids possess agonist melanocortin receptor activity. Peptides, 2003, 24, 1899-1908 (doi: 10.1016/j.peptides.2003.10.005). 

86. Joseph CG, Bauzo RM, Xiang Z, Haskell-Luevano C. Urea small molecule agonists on mouse melanocortin receptors. Bioorg. Med. Chem. Lett., 2003, 13, 2079-2082 (doi: 10.1016/s0960-894x(03)00318-4). 

87. Holder J, Haskell-Luevano C. Melanocortin tetrapeptides modified at the N-terminus, His, Phe, Arg, and Trp positions. Ann. NY Acad. Sci., 2003, 994, 36-48 (doi: 10.1111/j.1749-6632.2003.tb03160.x). 

88. Holder JR, Marques FF, Xiang Z, Bauzo RM, Haskell-Luevano C. Characterization of aliphatic, cyclic, and aromatic N-terminally "capped" His-DPhe-Arg-Trp-NH2 tetrapeptides at the melanocortin receptors. Eur. J. Pharmacol., 2003, 462, 41-52 (doi: 10.1016/s0014-2999(03)01322-0). 

89. Joseph CG, Bauzo RM, Xiang Z, Shaw AM, Millard WJ, Haskell-Luevano C. Elongation studies of the human agouti-related protein (AGRP) core decapeptide (Yc[CRFFNAFC]Y) results in antagonism at the mouse melanocortin-3 receptor. Peptides, 2003, 24, 263-270 (doi: 10.1016/s0196-9781(03)00030-5). 

90. Holder JR, Xiang Z, Bauzo RM, Haskell-Luevano C. Structure-activity relationships of the melanocortin tetrapeptide Ac-His-DPhe-Arg-Trp-NH2 at the mouse melanocortin receptors. Part 3: Modifications at the Arg position. Peptides, 2003, 24, 73-82 (doi: 10.1016/s0196-9781(02)00278-4). 

2002

91. Holder JR, Xiang Z, Bauzo RM, Haskell-Luevano C. Structure-activity relationships of the melanocortin tetrapeptide Ac-His-DPhe-Arg-Trp-NH2 at the mouse melanocortin receptors. 4. Modifications at the Trp position. J. Med. Chem., 2002, 45, 5736-5744 (doi: 10.1021/jm020296e).

92. Bondebjerg J, Xiang Z, Bauzo RM, Haskell-Luevano C, Meldal M. A solid-phase approach to mouse melanocortin receptor agonists derived from a novel thioether cyclized peptidomimetic scaffold. J. Am. Chem. Soc., 2002, 124, 11046-11055 (doi: 10.1021/ja0123913). 

93. Holder JR, Bauzo RM, Xiang Z, Haskell-Luevano C. Structure-activity relationships of the melanocortin tetrapeptide Ac-His-DPhe-Arg-Trp-NH2 at the mouse melanocortin receptors. Part 2: Modifications at the Phe position. J. Med. Chem., 2002, 45, 3073-3081 (doi: 10.1021/jm010524p). 

94. Holder JR, Bauzo RM, Xiang Z, Haskell-Luevano C. Structure-activity relationships of the melanocortin tetrapeptide Ac-His-DPhe-Arg-Trp-NH2 at the mouse melanocortin receptors. 1. Modifications at the His position. J. Med. Chem., 2002, 45, 2801-2810 (doi: 10.1021/jm0104872).

2001

95. Thirumoorthy R, Holder JR, Bauzo RM, Richards NG, Edison AS, Haskell-Luevano C. Novel agouti-related-protein-based melanocortin-1 receptor antagonist. J. Med. Chem., 2001, 44, 4114-4124 (doi: 10.1021/jm010215z).

96. Haskell-Luevano C, Holder JR, Monck EK, Bauzo RM. Characterization of melanocortin NDP-MSH agonist peptide fragments at the mouse central and peripheral melanocortin receptors. J. Med. Chem., 2001, 44, 2247-2252 (doi: 10.1021/jm010061n). 

97. Haskell-Luevano C, Cone RD, Monck EK, Wan YP. Structure activity studies of the melanocortin-4 receptor by in vitro mutagenesis: Identification of agouti-related protein (AGRP), melanocortin agonist and synthetic peptide antagonist interaction determinants. Biochemistry, 2001, 40, 6164-6179 (doi: 10.1021/bi010025q). 

98. Haskell-Luevano C, Monck EK. Agouti-related protein functions as an inverse agonist at a constitutively active brain melanocortin-4 receptor. Regul. Pept., 2001, 99, 1-7 (doi: 10.1016/s0167-0115(01)00234-8). 

2000

99. Haskell-Luevano C, Monck EK, Wan YP, Schentrup AM. The agouti-related protein decapeptide (Yc[CRFFNAFC]Y) possesses agonist activity at the murine melanocortin-1 receptor. Peptides, 2000, 21, 683-689 (doi: 10.1016/s0196-9781(00)00194-7). 

100. Haskell-Luevano C, Lim S, Yuan W, Cone RD, Hruby VJ. Structure activity studies of the melanocortin antagonist SHU9119 modified at the 6, 7, 8, and 9 positions. Peptides, 2000, 21, 49-57 (doi: 10.1016/s0196-9781(99)00167-9). 

1999

101. Haskell-Luevano C, Rosenquist A, Souers A, Khong KC, Ellman JA, Cone RD. Compounds that activate the mouse melanocortin-1 receptor identified by screening a small molecule library based upon the beta-turn. J. Med. Chem., 1999, 42, 4380-4387 (doi: 10.1021/jm990190s).

102. Hadley ME, Haskell-Luevano C. The proopiomelanocortin system. Ann. NY Acad. Sci., 1999, 885, 1-21 (doi: 10.1111/j.1749-6632.1999.tb08662.x).

103. Chen P, Li C, Haskell-Luevano C, Cone RD, Smith MS. Altered expression of agouti-related protein and its colocalization with neuropeptide Y in the arcuate nucleus of the hypothalamus during lactation. Endocrinology, 1999, 140, 2645-2650 (doi: 10.1210/endo.140.6.6829). 

104. Haskell-Luevano C, Chen P, Li C, Chang K, Smith MS, Cameron JL, Cone RD. Characterization of the neuroanatomical distribution of agouti-related protein immunoreactivity in the rhesus monkey and the rat. Endocrinology, 1999, 140, 1408-1415 (doi: 10.1210/endo.140.3.6544).

1997

105. Yang Yk, Dickinson C, Haskell-Luevano C, Gantz I. Molecular basis for the interaction of [Nle4,DPhe7]melanocyte stimulating hormone with the human melanocortin-1 receptor. J. Biol. Chem., 1997, 272, 23000-23010 (doi: 10.1074/jbc.272.37.23000).

106. Haskell-Luevano C, Toth K, Boteju L, Job C, Castrucci AM, Hadley ME, Hruby VJ. β-Methylation of the Phe7 and Trp9 melanotropin side chain pharmacophores affects ligand-receptor interactions and prolonged biological activity. J. Med. Chem., 1997, 40, 2740-2749 (doi: 10.1021/jm970018t).

107. Haskell-Luevano C, Hendrata S, North C, Sawyer TK, Hadley ME, Hruby VJ, Dickinson C, Gantz I. Discovery of prototype peptidomimetic agonists at the human melanocortin receptors MC1R and MC4R. J. Med. Chem., 1997, 40, 2133-2139 (doi: 10.1021/jm960840h).

108. Haskell-Luevano C, Nikiforovich G, Sharma SD, Yang YK, Dickinson C, Hruby VJ, Gantz I. Biological and conformational examination of stereochemical modifications using the template melanotropin peptide, Ac-Nle-c[Asp-His-Phe-Arg-Trp-Ala-Lys]-NH2, on human melanocortin receptors. J. Med. Chem., 1997, 40, 1738-1748 (doi: 10.1021/jm960845e). 

109. Hruby VJ, Li G, Haskell-Luevano C, Shenderovich M. Design of peptides, proteins, and peptidomimetics in chi space. Biopolymers, 1997, 43, 219-266 (doi: 10.1002/(SICI)1097-0282(1997)43:3<219::AID-BIP3>3.0.CO;2-Y).

1996

110. Haskell-Luevano C, Sawyer TK, Trumpp-Kallmeyer S, Bikker JA, Humblet C, Gantz I, Hruby VJ. Three-dimensional molecular models of the hMC1R melanocortin receptor: Complexes with melanotropin peptide agonists. Drug Des. Discov., 1996, 14, 197-211. 

111. Hadley ME, Hruby VJ, Jiang J, Sharma SD, Fink JL, Haskell-Luevano C, Bentley DL, al-Obeidi F, Sawyer TK. Melanocortin receptors: Identification and characterization by melanotropic peptide agonists and antagonists. Pigment Cell Res., 1996, 9, 213-234 (doi: 10.1111/j.1600-0749.1996.tb00111.x).

112. Boteju LW, Nikiforovich GV, Haskell-Luevano C, Fang SN, Zalewska T, Stropova D, Yamamura HI, Hruby VJ. The use of topographical constraints in receptor mapping: investigation of the topographical requirements of the tryptophan 30 residue for receptor binding of Asp-Tyr-DPhe-Gly-Trp-(N-Me)Nle-Asp-Phe-NH2 (SNF 9007), a cholecystokinin (26-33) analogue that binds to both CCK-B and δ-opioid receptors. J. Med. Chem., 1996, 39, 4120-4124 (doi: 10.1021/jm960078j). 

113. Haskell-Luevano C, Miwa H, Dickinson C, Hadley ME, Hruby VJ, Yamada T, Gantz I. Characterizations of the unusual dissociation properties of melanotropin peptides from the melanocortin receptor, hMC1R. J. Med. Chem., 1996, 39, 432-435 (doi: 10.1021/jm950407s). 

114. Haskell-Luevano C, Sawyer TK, Hendrata S, North C, Panahinia L, Stum M, Staples DJ, Castrucci AM, Hadley MF, Hruby VJ. Truncation studies of α-melanotropin peptides identify tripeptide analogues exhibiting prolonged agonist bioactivity. Peptides, 1996,17, 995-1002 (doi: 10.1016/0196-9781(96)00141-6). 

1995

115. Haskell-Luevano C, Boteju LW, Miwa H, Dickinson C, Gantz I, Yamada T, Hadley ME, Hruby VJ. Topographical modification of melanotropin peptide analogues with β-methyltryptophan isomers at position 9 leads to differential potencies and prolonged biological activities. J. Med. Chem., 1995, 38, 4720-4729 (doi: 10.1021/jm00023a012).

116. Haskell-Luevano C, Shenderovich MD, Sharma SD, Nikiforovich GV, Hadley ME, Hruby VJ. Design, synthesis, biology, and conformations of bicyclic α-melanotropin analogues. J. Med. Chem., 1995, 38, 1736-1750 (doi: 10.1021/jm00010a018). 

117. Haskell-Luevano C, Miwa H, Dickinson C, Hruby VJ, Yamada T, Gantz I. Binding and cAMP studies of melanotropin peptides with the cloned human peripheral melanocortin receptor, hMC1R. Biochem. Biophys. Res. Commun., 1994, 204, 1137-1142 (doi: 10.1006/bbrc.1994.2581).