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Revealing the Indispensable Role of the RFamide Functionality using a Novel Acid Labile Benzofuranone based Amine (ALBA) Linker.

Authors :
Mudd, Gemma
Hendrikse, Megan
Shave, Steven
Houston, Douglas R
Millar, Robert P
Auer, Manfred
Source :
Helvetica Chimica Acta. Apr2024, Vol. 107 Issue 4, p1-7. 7p.
Publication Year :
2024

Abstract

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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
0018019X
Volume :
107
Issue :
4
Database :
Academic Search Index
Journal :
Helvetica Chimica Acta
Publication Type :
Academic Journal
Accession number :
176608948
Full Text :
https://doi.org/10.1002/hlca.202300204