Mudd, GemmaHendrikse, MeganShave, StevenHouston, Douglas R.Millar, Robert P.Auer, Manfred2024-06-252024-06-252024-04Mudd, G., Hendrikse, M., Shave, S. et al. 2024, 'Revealing the indispensable role of the RFamide functionality using a novel acid labile benzofuranone based amine (ALBA) linker', Helvetica Chimica Acta, vol. 107, no. 4, art. e202300204, pp. 1-7, doi : 10.1002/hlca.202300204.0018-019X (print)1522-2675 (online)10.1002/hlca.202300204http://hdl.handle.net/2263/96632DATA AVAILABILITY STATEMENT : The data that support the findings of this study are available from the corresponding author upon reasonable request.This article also appears in: Andrea Vasella 80th Birthday Biochemistry and Medicinal Chemistry Organic and Organometallic Chemistry.The RFamide family of peptides represents an important class of GPCR ligand neuropeptides covering a wide range of biological functions. While many analogues of the highly conserved C-terminal RFamide motif within this peptide class have been synthesized and their functional significance elucidated, additional exploration of the structure activity relationship is of value. We have developed a novel linker for solid phase peptide synthesis (SPPS) which is able to anchor amine functionalised compounds for further elaboration. The acid labile benzofuranone based amine (ALBA) linker (5-(3-aminopropylcarbamoyl)-2-[[tert-butyl(diphenyl)silyl]oxymethyl]benzoic acid) is compatible with Fmoc based SPPS and has two cleavage modes. As a proof of concept, the ALBA linker was used to successfully synthesise a novel analogue of Kisspeptin 10, the natural ligand for GPCR54, whereby the natural RFamide motif was replaced with an RFamine. Biological evaluation of the amine-containing analogue revealed that the group is not compatible with receptor activation.en© 2024 The Authors. Helvetica Chimica Acta published by Wiley-VHCA AG.Cleavable linkerKisspeptinGPR54G-protein coupled receptor (GPCR)RFamideSolid phase peptide synthesis (SPPS)Acid labile benzofuranone based amine (ALBA)SDG-03: Good health and well-beingArticle