Beta amino acid-modified and fluorescently labelled kisspeptin analogues with potent KISS1R activity.
Kisspeptin analogues with improved metabolic stability may represent important ligands in the study of the kisspeptin/KISS1R system and have therapeutic potential. In this paper we assess the activity of known and novel kisspeptin analogues utilising a dual luciferase reporter assay in KISS1R-transfected HEK293T cells. In general terms the results reflect the outcomes of other assay formats and a number of potent agonists were identified among the analogues, including β(2) -hTyr-modified and fluorescently labelled forms. We also showed, by assaying kisspeptin in the presence of protease inhibitors, that proteolysis of kisspeptin activity within the reporter assay itself may diminish the agonist outputs. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.
Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, 3052, Australia.
M A
MA
Camerino
Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, 3052, Australia.
M
M
Liu
Brain Research Institutes, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, Selangor, 47500, Malaysia.
S
S
Moriya
Brain Research Institutes, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, Selangor, 47500, Malaysia.
T
T
Kitahashi
Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, 3052, Australia.
A
A
Mahgoub
Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, 3052, Australia.
S J
SJ
Mountford
Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, 3052, Australia.
D K
DK
Chalmers
Brain Research Institutes, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, Selangor, 47500, Malaysia.
T
T
Soga
Brain Research Institutes, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, Selangor, 47500, Malaysia.
I S
IS
Parhar
Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, 3052, Australia.
P E
PE
Thompson
D000596:Amino Acids / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000737:chemistry; D057809:HEK293 Cells; D006801:Humans; D059648:Kisspeptins / Q000819:agonists*; D008024:Ligands; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000378:metabolism*; D000074502:Receptors, Kisspeptin-1
D000596:Amino Acids; D005456:Fluorescent Dyes; C106628:KISS1 protein, human; C118688:KISS1R protein, human; D059648:Kisspeptins; D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1
KISS1R agonist; beta amino acids; fluorescent peptides; kisspeptin