Fluorescent IGF-II analogues for FRET-based investigations into the binding of IGF-II to the IGF-1R

• Published in: Organic & biomolecular chemistry Vol. 14; no. 9; pp. 2698 - 2705
• Main Authors: Cottam Jones, J M, Harris, P W R, Scanlon, D B, Forbes, B E, Brimble, M A, Abell, A D
• Format: Journal Article
• Language: English
• Published: England 01.01.2016
• Subjects: Binding Sites; Fluorescence; Fluorescence Resonance Energy Transfer; Insulin-Like Growth Factor II - analogs & derivatives; Insulin-Like Growth Factor II - chemistry; Molecular Structure; Receptor, IGF Type 1 - chemistry
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c5ob02110c

The interaction of IGF-II with the insulin receptor (IR) and type 1 insulin-like growth factor receptor (IGF-1R) has recently been identified as potential therapeutic target for the treatment of cancer. Understanding the interactions of IGF-II with these receptors is required for the development of potential anticancer therapeutics. This work describes an efficient convergent synthesis of native IGF-II and two non-native IGF-II analogues with coumarin fluorescent probes incorporated at residues 19 and 28. These fluorescent analogues bind with nanomolar affinities to the IGF-1R and are suitable for use in fluorescence resonance energy transfer (FRET) studies. From these studies the F19Cou IGF-II and F28Cou IGF-II proteins were identified as good probes for investigating the binding interactions of IGF-II with the IGF-1R and its other high affinity binding partners.