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 biologically inactive. Therefore [Tyr(0,) Gln(1,) Leu(17)]sauvagine (YQLS), in which the methionine was replaced with leucine was synthesized and labeled with (125)Iodine using chloramine-T. Mass spectroscopy revealed that chloramine-T-treatment did not oxidize YQLS. (125)I-YQLS bound with high affinity to cells expressing the murine CRF receptor 1 (CRFR1), CRF receptor 2 (CRFR2), and the mouse brain regions known to express both CRF receptors. (125)I-YQLS chemically cross-linked to CRFR1. In conclusion, (125)I-YQLS is oxidation-resistant, high affinity radioligand that can be chemically cross-linked to the CRF receptors.
Assil
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IQ
Endocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Shomali
M E
ME
Abou-Samra
A B
AB
D000595:Amino Acid Sequence; D029845:Amphibian Proteins; D000818:Animals; D001921:Brain / Q000378:metabolism; D019556:COS Cells; D002478:Cells, Cultured; D002700:Chloramines / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007455:Iodine / Q000494:pharmacology; D007930:Leucine / Q000737:chemistry; D008024:Ligands; D013058:Mass Spectrometry; D008715:Methionine / Q000737:chemistry; D051379:Mice; D008969:Molecular Sequence Data; D010100:Oxygen / Q000378:metabolism*; D036361:Peptide Hormones; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D018019:Receptors, Corticotropin-Releasing Hormone / Q000737:chemistry* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013388:Succinimides / Q000494:pharmacology; D014443:Tyrosine / Q000737:chemistry; D014579:Urotensins / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology
D029845:Amphibian Proteins; D002700:Chloramines; D003432:Cross-Linking Reagents; D018076:DNA, Complementary; D008024:Ligands; D036361:Peptide Hormones; D010455:Peptides; D018019:Receptors, Corticotropin-Releasing Hormone; D013388:Succinimides; D014579:Urotensins; D014665:Vasodilator Agents; D014443:Tyrosine; C025727:sauvagine; C029676:urotensin I; D007455:Iodine; D008715:Methionine; D000242:Cyclic AMP; D007930:Leucine; C030816:chloramine; D010100:Oxygen; C019358:disuccinimidyl suberate