Search

Your search keyword '"Mathre, Sarah S."' showing total 3 results
Start Over Author "Mathre, Sarah S."
3 results on '"Mathre, Sarah S."'

2. Discovery of a Pan-Melanocortin Receptor Antagonist [Ac-DPhe(pI)-Arg-Nal(2′)-Orn-NH2] at the MC1R, MC3R, MC4R, and MC5R that Mediates an Increased Feeding Response in Mice and a 40-Fold Selective MC1R Antagonist [Ac-DPhe(pI)-DArg-Nal(2′)-Arg-NH2]

Author

Ericson, Mark D., Tran, Linh T., Mathre, Sarah S., Freeman, Katie T., Holdaway, Kelsey, John, Kristen, Lunzer, Mary M., Bouchard, Jacob L., and Haskell-Luevano, Carrie

Abstract

Discovery of pan-antagonist ligands for the melanocortin receptors will help identify the physiological activities controlled by these receptors. The previously reported MC3R/MC4R antagonist Ac-DPhe(pI)-Arg-Nal(2′)-Arg-NH2was identified herein, for the first time, to possess MC1R and MC5R antagonist activity. Further structure–activity relationship studies probing the second and fourth positions were performed toward the goal of identifying potent melanocortin antagonists. Of the 21 tetrapeptides synthesized, 13 possessed MC1R, MC3R, MC4R, and MC5R antagonist activity. Three tetrapeptides were more than 10-fold selective for the mMC1R, including 8(LTT1-44, Ac-DPhe(pI)-DArg-Nal(2′)-Arg-NH2) that possessed 80 nM mMC1R antagonist potency and was at least 40-fold selective over the mMC3R, mMC4R, and mMC5R. Nine tetrapeptides were selective for the mMC4R, including 14[SSM1-8, Ac-DPhe(pI)-Arg-Nal(2′)-Orn-NH2] with an mMC4R antagonist potency of 1.6 nM. This compound was administered IT into mice, resulting in a dose-dependent increase in the food intake and demonstrating the in vivo utility of this compound series.

Published
2024
Full Text
View/download PDF

3. Discovery of a Pan-Melanocortin Receptor Antagonist [Ac-DPhe(pI)-Arg-Nal(2')-Orn-NH 2 ] at the MC1R, MC3R, MC4R, and MC5R that Mediates an Increased Feeding Response in Mice and a 40-Fold Selective MC1R Antagonist [Ac-DPhe(pI)-DArg-Nal(2')-Arg-NH 2 ].

Author

Ericson MD, Tran LT, Mathre SS, Freeman KT, Holdaway K, John K, Lunzer MM, Bouchard JL, and Haskell-Luevano C

Subjects
Animals, Mice, Oligopeptides chemistry, Receptors, Melanocortin, Structure-Activity Relationship, Receptor, Melanocortin, Type 4, Receptor, Melanocortin, Type 3, Melanocortins
Abstract

Discovery of pan-antagonist ligands for the melanocortin receptors will help identify the physiological activities controlled by these receptors. The previously reported MC3R/MC4R antagonist Ac-DPhe(pI)-Arg-Nal(2')-Arg-NH 2 was identified herein, for the first time, to possess MC1R and MC5R antagonist activity. Further structure-activity relationship studies probing the second and fourth positions were performed toward the goal of identifying potent melanocortin antagonists. Of the 21 tetrapeptides synthesized, 13 possessed MC1R, MC3R, MC4R, and MC5R antagonist activity. Three tetrapeptides were more than 10-fold selective for the mMC1R, including 8 (LTT1-44, Ac-DPhe(pI)-DArg-Nal(2')-Arg-NH 2 ) that possessed 80 nM mMC1R antagonist potency and was at least 40-fold selective over the mMC3R, mMC4R, and mMC5R. Nine tetrapeptides were selective for the mMC4R, including 14 [SSM1-8, Ac-DPhe(pI)-Arg-Nal(2')-Orn-NH 2 ] with an mMC4R antagonist potency of 1.6 nM. This compound was administered IT into mice, resulting in a dose-dependent increase in the food intake and demonstrating the in vivo utility of this compound series.

Published
2023
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results