Beta amino acid-modified and fluorescently labelled kisspeptin analogues with potent KISS1R activity.
Camerino. M A MA; Liu. M M; Moriya. S S; Kitahashi. T T; Mahgoub. A A; Mountford. S J SJ; Chalmers. D K DK; Soga. T T; Parhar. I S IS; Thompson. P E PE
Key Findings
- Beta‑amino acid‑modified kisspeptin analogues retain high KISS1R agonist activity.
- Fluorescently labelled kisspeptin variants can also act as potent agonists.
- Proteolysis (enzyme breakdown) of kisspeptin in the assay reduces measured activity, suggesting stability is a key factor.
Practical Outcomes
- For DIY biohackers, the study suggests that chemically tweaking kisspeptin (e.g., adding beta‑amino acids) could make it last longer in the body and stay active, but no human dosing or safety data are provided. Until such modified peptides are available and tested in people, the findings are mainly of scientific interest rather than a ready‑to‑use protocol.
Summary
Researchers made new versions of the kisspeptin peptide that are more resistant to breakdown and still strongly activate its receptor in lab cells. Some of these modified peptides, including ones with a beta‑amino acid tweak or a fluorescent tag, worked especially well. They also showed that normal kisspeptin can get degraded by enzymes in the test, which can lower its apparent activity.
Abstract
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.
Study Information
pubmed
2016
2016-06-01T00:00:00.000Z
10.1002/psc.2883
5
44