Feyen J H, Cardinaux F, Gamse R, Bruns C, Azria M, Trechsel U
Sandoz Pharma Ltd, Basel, Switzerland.
Biochem Biophys Res Commun. 1992 Aug 31;187(1):8-13. doi: 10.1016/s0006-291x(05)81450-0.
Structural requirements for binding to the bone calcitonin (CT) receptor and for CT bioactivity both in vitro and in vivo were assessed for a series of N-terminally truncated, N alpha-acetylated, fragments of salmon calcitonin (sCT). Sequential deletion of amino acid residues from the amino-terminus of [Ala7]sCT-(2-32) peptide amide first led to partial agonists and, upon deletion of residues 1 to 7, to a high affinity antagonist, N alpha-acetyl-sCT-(8-32)-NH2. The presence of two separate domains within the sCT sequence is proposed: (I) a binding domain comprising residues 9-32 and (II) an activation domain requiring residues 3 to 6. N alpha-acetyl-sCT-(8-32)-NH2, in several bioassays including plasminogen activator release from LLC-PK1 cells (pA2 = 7.31), cAMP production in UMR-106-06 cells (pA2 = 7.81) and in the fetal rat long bone resorption assay showed potent antagonistic properties.
对一系列N端截短、Nα-乙酰化的鲑鱼降钙素（sCT）片段，评估了其在体外和体内与骨降钙素（CT）受体结合以及CT生物活性的结构要求。从[Ala7]sCT-(2-32)肽酰胺的氨基末端依次删除氨基酸残基，首先产生部分激动剂，在删除残基1至7后，产生高亲和力拮抗剂Nα-乙酰基-sCT-(8-32)-NH2。推测sCT序列内存在两个独立结构域：（I）包含残基9-32的结合结构域和（II）需要残基3至6的激活结构域。在包括从LLC-PK1细胞释放纤溶酶原激活剂（pA2 = 7.31）、UMR-106-06细胞中cAMP产生（pA2 = 7.81）以及胎鼠长骨吸收试验在内的几种生物测定中，Nα-乙酰基-sCT-(8-32)-NH2显示出强大的拮抗特性。
