An oxidation resistant radioligand for corticotropin-releasing factor receptors

The methionine residues in Tyr-corticotropin-releasing factor (CRF) and Tyr -sauvagine radioligands are subject to oxidation, which renders them biolog ically inactive. Therefore [Tyr(0). Gln(1). Leu(17)] sauvagine (YQLS), in w hich the methionine was replaced with leucine was synthesized and labeled w ith (125)lodine using chloramine-T. Mass spectroscopy revealed that chloram ine-T-treatment did not oxidize YQLS. I-125-YQLS bound with high affinity t o cells expressing the murine CRF receptor 1 (CRFR1), CRF receptor 2 (CRFR2 ), and the mouse brain regions known to express both CRF receptors. I-125-Y QLS chemically cross-linked to CRFR1. In conclusion, I-125-YQLS is oxidatio n-resistant, high affinity radioligand that can be chemically cross-linked to the CRF receptors. (C) 2001 Elsevier Science Inc. All rights reserved.