Design and synthesis of fluorescent probes for GPR54

Kaneda, Masato; Misu, Ryosuke; Ohno, Hiroaki; Hirasawa, Akira; Ieda, Nahoko; Uenoyama, Yoshihisa; Tsukamura, Hiroko; Maeda, Kei‐ichiro; Oishi, Shinya; Fujii, Nobutaka

doi:10.1016/j.bmc.2014.04.052

Cited by 7 publications

(6 citation statements)

References 26 publications

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“…Kaneda et al recently described alternate fluorescently labelled kisspeptin analogues through N ‐terminal derivatization of KP‐14 and KP‐52. The retention of agonist activity with the tetramethylrhodmaine and rhodamine green labels is consistent with our data here …”

Section: Discussionsupporting

confidence: 91%

“…The retention of agonist activity with the tetramethylrhodmaine and rhodamine green labels is consistent with our data here. [25] We also examined the use of β-amino acids as a means of constraining the short pentapeptide agonists in the hope that it may confer metabolic stability while also retaining a bioactive conformer. The changes to the structure proved very deleterious to FBz-Phe-Gly-Leu-Arg-β 2 hPhe-NH 2 774 .3 Inactive 11 FBz-Phe-Gly-Leu-Arg-β 2 hTrp-NH 2 812.9 >1000 b 12…”

Section: Discussionmentioning

confidence: 99%

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Beta amino acid‐modified and fluorescently labelled kisspeptin analogues with potent KISS1R activity

Camerino

Liu

Moriya

et al. 2016

Journal of Peptide Science

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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.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Beta amino acid‐modified and fluorescently labelled kisspeptin analogues with potent KISS1R activity

Camerino

Liu

Moriya

et al. 2016

Journal of Peptide Science

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“…However, a significant receptor binding of the fluorescence-labelled ligand could only be detected at 50 nM or higher concentrations of Sulfo-Cy 5 -KP-18. A similar result was reported for tetramethylrhodamine and rhodamine green-labelled KP-14 or KP-52 [ 43 ]. The development of the functional Sulfo-Cy 5 -KP-18 allowed us to determine potential binding of the KP phosphinic peptides via their inhibition to Sulfo-Cy 5 -KP-18-induced receptor internalisation.…”

Section: Discussionsupporting

confidence: 88%

Functional examination of novel kisspeptin phosphinic peptides

et al. 2018

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Kisspeptins acting on their cognate G protein-coupled receptor, kisspeptin receptor, play important roles in the suppression of cancer cell metastasis and regulation of the reproductive system, and therefore are important for therapeutic intervention. All native functional human kisspeptins (kisspeptin-54, kisspsptin-14 and kisspeptin-13) share the 10 amino acids of kisspeptin-10 at their C-terminus (45–54). However, they are inactivated rapidly by matrix metalloproteinases (MMPs) through the cleavage of the peptide bond between glycine51 and leucine52, which limits their clinical applications. Development of MMP-resistant analogues of kisspeptins may provide better therapeutic outputs. In the present study, two kisspeptin phosphinic peptides were designed and synthesized, and their ability to induce phosphorylation of ERK1/2 through kisspeptin receptor and their inhibition on MMP-2 and MMP-9 whose activity correlates with cancer metastasis were assessed. The results showed that one analogue, phosphinic kisspeptin R isomer (PKPR), exhibited kisspeptin receptor-agonistic activity and also inhibitory activity on MMP-2, indicating that PKPR may serve as a lead for the further development of kisspeptin analogues for therapeutic purpose.

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“…High-affinity agonist (including metastin analogs and fluorobenzoyl pentapeptides) [ 71 – 75 , 79 ] and antagonist (including 2-acylamino-4,6-diphenyl-pyridine derivatives) [ 76 – 78 ] ligands are known for the KiSS-1 receptor (KISS1R). Recently, fluorescently labeled ligands have been developed for studying KISS1R [ 59 – 61 ]. In addition, a series of 2-hydroxydiarylamide derivatives have been reported as potential TMPRSS4 serine protease inhibitors [ 80 ].…”

Section: Discussionmentioning

confidence: 99%

Cell-surface marker discovery for lung cancer

et al. 2017

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Lung cancer is the leading cause of cancer deaths in the United States. Novel lung cancer targeted therapeutic and molecular imaging agents are needed to improve outcomes and enable personalized care. Since these agents typically cannot cross the plasma membrane while carrying cytotoxic payload or imaging contrast, discovery of cell-surface targets is a necessary initial step. Herein, we report the discovery and characterization of lung cancer cell-surface markers for use in development of targeted agents. To identify putative cell-surface markers, existing microarray gene expression data from patient specimens were analyzed to select markers with differential expression in lung cancer compared to normal lung. Greater than 200 putative cell-surface markers were identified as being overexpressed in lung cancers. Ten cell-surface markers (CA9, CA12, CXorf61, DSG3, FAT2, GPR87, KISS1R, LYPD3, SLC7A11 and TMPRSS4) were selected based on differential mRNA expression in lung tumors vs. non-neoplastic lung samples and other normal tissues, and other considerations involving known biology and targeting moieties. Protein expression was confirmed by immunohistochemistry (IHC) staining and scoring of patient tumor and normal tissue samples. As further validation, marker expression was determined in lung cancer cell lines using microarray data and Kaplan–Meier survival analyses were performed for each of the markers using patient clinical data. High expression for six of the markers (CA9, CA12, CXorf61, GPR87, LYPD3, and SLC7A11) was significantly associated with worse survival. These markers should be useful for the development of novel targeted imaging probes or therapeutics for use in personalized care of lung cancer patients.

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Design and synthesis of fluorescent probes for GPR54

Cited by 7 publications

References 26 publications

Beta amino acid‐modified and fluorescently labelled kisspeptin analogues with potent KISS1R activity

Beta amino acid‐modified and fluorescently labelled kisspeptin analogues with potent KISS1R activity

Functional examination of novel kisspeptin phosphinic peptides

Cell-surface marker discovery for lung cancer

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