TY - JOUR
T1 - Structure activity studies of the melanocortin antagonist SHU9119 modified at the 6, 7, 8, and 9 positions
AU - Haskell-Luevano, Carrie
AU - Lim, Sejin
AU - Yuan, Wei
AU - Cone, Roger D.
AU - Hruby, Victor J.
N1 - Funding Information:
This work was supported in part by U.S. Public Health Service Grants DK17420 (V.J.H.) and AR42415 (R.D.C.). C.H.L. was supported in part by U.S. Public Health Service Grant DK09231 and is a recipient of a Burroughs Wellcome Fund Career Award in the Biomedical Sciences.
PY - 2000/1
Y1 - 2000/1
N2 - The melanocortin system is involved in the regulation of several diverse physiological pathways, including energy homeostasis. Several synthetic peptide analogs have been designed, synthesized, and pharmacologically characterized at the mouse melanocortin receptor subtypes MC1R, MC3R, MC4R, and MC5R. These peptides incorporate modifications of the melanocortin core amino acids His-Phe-Arg-Trp by using the cyclic lactam templates of the lead structures MTII and SHU9119. Analogs containing DNal(2') at position 7 resulted in partial agonist and antagonistic activities at the mMC3R while possessing full antagonistic activities at the mMC4R. Recently, the melanocortin-5 receptor (MC5R) has been demonstrated to have a role in the regulation of exocrine gland function. This study has characterized the following analogs of SHU9119 that possess antagonist activity at the MC5R: Ac-Nle-c[Asp-(1-Me)His6-DNal(2')7-Arg-Trp-Lys]-NH2, pA2 = 7.1; Ac-Nle- c[Asp-(1-Me)His6-DNal(2')7-Arg-Nal(2')9-Lys]-NH2, pA2 = 7.2; and Ac-Nle- c[Asp-Trp6-DNal(2')7-Arg-Nal(2')9-Lys]-NH2, pA2 = 6.6. (C) 2000 Elsevier Science Inc.
AB - The melanocortin system is involved in the regulation of several diverse physiological pathways, including energy homeostasis. Several synthetic peptide analogs have been designed, synthesized, and pharmacologically characterized at the mouse melanocortin receptor subtypes MC1R, MC3R, MC4R, and MC5R. These peptides incorporate modifications of the melanocortin core amino acids His-Phe-Arg-Trp by using the cyclic lactam templates of the lead structures MTII and SHU9119. Analogs containing DNal(2') at position 7 resulted in partial agonist and antagonistic activities at the mMC3R while possessing full antagonistic activities at the mMC4R. Recently, the melanocortin-5 receptor (MC5R) has been demonstrated to have a role in the regulation of exocrine gland function. This study has characterized the following analogs of SHU9119 that possess antagonist activity at the MC5R: Ac-Nle-c[Asp-(1-Me)His6-DNal(2')7-Arg-Trp-Lys]-NH2, pA2 = 7.1; Ac-Nle- c[Asp-(1-Me)His6-DNal(2')7-Arg-Nal(2')9-Lys]-NH2, pA2 = 7.2; and Ac-Nle- c[Asp-Trp6-DNal(2')7-Arg-Nal(2')9-Lys]-NH2, pA2 = 6.6. (C) 2000 Elsevier Science Inc.
KW - MTII
KW - Melanocortin antagonists
KW - Melanotropin
KW - SHU9119
KW - α-MSH
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U2 - 10.1016/S0196-9781(99)00167-9
DO - 10.1016/S0196-9781(99)00167-9
M3 - Article
C2 - 10704719
AN - SCOPUS:0033998015
SN - 0196-9781
VL - 21
SP - 49
EP - 57
JO - Peptides
JF - Peptides
IS - 1
ER -