Biologically active peptides have long been isolated from natural sources using the chromatographie separation and purification methods to identify new endogenous ligands. Recently, advancements in genomic research have led to new strategies of discovering novel peptides, notably using bioinformatical DNA sequence analysis techniques. Late in 2003, two peptides termed Salusin-α code 4417 and Salusin-β code 4418 were discovered using this modern technique; that is, the selection of putative secretory prepropeptides, which possess the structural features of processing signals resulting in mature peptides with less than 40 amino acid residues1). Salusin-α was predicted to be a 28-residue peptide with an amidated carboxyl-terminus, while salusin-β was predicted to be a 20-residue peptide with a free carboxyl-terminus. These two peptides were encoded in the order of salusin-β and salusin-α from a single mRNA transcribed from TOR2A.
Preprosalusin: AWD ………. RK-[ salusin-β]-RR-[salusin-α]G* *carboxyl-terminal Gly in the above sequence is the precursor of the amide structure. salusin-α: SGALPP AP AAPRP ALRAQRAGP AGPGAK-NH2 salusin-β: AIFIFIRWLLKLGHHGRAPP
It has been reported that chemically synthesized salusin-α and salusin-β exert the following biological activities: i) mitogenic effects in rat vascular smooth muscle cells and fibroblasts, probably through mutually distinct receptors, ii) dose-dependent hypotensive activity in rats (1-10 nmol/kg for salusin-α and 0.1-1 nmol/kg for salusin-β), and iii) [Arg8]-vasopressin releasing activity in perfused rat pituitaries (exclusive activity of salusin-β in a dose-dependent manner [0.01-100 nM)). Immunohistochemical experiments showed that both of these peptides are present in numerous tissues, including kidney as the major source. Salusin-α and salusin-β should become essential peptides as “newly identified regulators of hemodynamics and mitogenesis", because these peptides exist in many tissues and in body fluids in humans.
1) M. Shichiri, S. Ishimaru, T. Ota, T. Nishikawa, T. Isogai and Y. Hirata, Nat. Med., 9, 1166 (2003). (Original)
4417-s 0.1 mg Ser - Gly - Ala - Leu - Pro - Pro - Ala - Pro - Ala - Ala - Pro - Arg - Pro - Ala - Leu - Arg - Ala - Gln - Arg - Ala - Gly - Pro - Ala - Gly - Pro - Gly - Ala - Lys - NH2
