Stresscopin and Urocortin two novel specific ligands for CRF receptor type 2
The recently deposited genome sequences afford a novel procedure for discovering putative ligands utilizing the sequence homology with existing ligands. This promising method has now been applied to the discovery of the selective ligands for the corticotropin releasing factor (CRF) receptor type 2 (CRF-R2). CRF receptors, CRF-R1 and CRF-R2, belong to the superfamily of G-protein coupled receptors with seven transmembrane domains. A well-established ligand for CRF-R1 is CRF [Code 4136 (Human) and Code 4111 (ovine)], whereas urocortin [Code 4328 (Human) and Code 4327 (Rat)] is the non-selective but potent ligands for CRF-R1 and CRF-R2 [Endocrinology, 137, 2167 (1996)]. Selective ligand(s) with distinct CRF-R2 preference have not been identified until very recently, when two groups proposed urocortin II/III [Proc. Natl. Acad. Sci. USA, 98, 2843 (2001), ibid. 98, 7570 (2001)] or stresscopin / stresscopin-related peptide, discovered by independently applying the above mentioned method [Nat. Med., 7, 605 (2001)].
4387-s 0.1 mg Thr - Lys - Phe - Thr - Leu - Ser - Leu - Asp - Val - Pro - Thr - Asn - Ile - Met - Asn - Leu - Leu - Phe - Asn - Ile - Ala - Lys - Ala - Lys - Asn - Leu - Arg - Ala - Gln - Ala - Ala - Ala - Asn - Ala - His - Leu - Met - Ala - Gln - Ile - NH2
4388-s 0.1 mg His - Pro - Gly - Ser - Arg - Ile - Val - Leu - Ser - Leu - Asp - Val - Pro - Ile - Gly - Leu - Leu - Gln - Ile - Leu - Leu - Glu - Gln - Ala - Arg - Ala - Arg - Ala - Ala - Arg - Glu - Gln - Ala - Thr - Thr - Asn - Ala - Arg - Ile - Leu - Ala - Arg - Val - NH2
4328-s 0.1 mg Asp - Asn - Pro - Ser - Leu - Ser - Ile - Asp - Leu - Thr - Phe - His - Leu - Leu - Arg - Thr - Leu - Leu - Glu - Leu - Ala - Arg - Thr - Gln - Ser - Gln - Arg - Glu - Arg - Ala - Glu - Gln - Asn - Arg - Ile - Ile - Phe - Asp - Ser - Val - NH2
4327-s 0.1 mg Asp - Asp - Pro - Pro - Leu - Ser - Ile - Asp - Leu - Thr - Phe - His - Leu - Leu - Arg - Thr - Leu - Leu - Glu - Leu - Ala - Arg - Thr - Gln - Ser - Gln - Arg - Glu - Arg - Ala - Glu - Gln - Asn - Arg - Ile - Ile - Phe - Asp - Ser - Val - NH2
4383-s 0.1 mg Val - Ile - Leu - Ser - Leu - Asp - Val - Pro - Ile - Gly - Leu - Leu - Arg - Ile - Leu - Leu - Glu - Gln - Ala - Arg - Tyr - Lys - Ala - Ala - Arg - Asn - Gln - Ala - Ala - Thr - Asn - Ala - Gln - Ile - Leu - Ala - His - Val - NH2