[1-deamino-4-cyclohexylalanine][arginine⁸]vasopressin

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: [1-deamino-4-cyclohexylalanine][arginine⁸]vasopressin
• 英文别名: [deamino-Cys¹][Cha⁴]arginine vasopressin；d[Cha⁴]AVP；d[Cha4]AVP；(2S)-N-[(2S)-1-[(2-amino-2-oxoethyl)amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-1-[(4R,7S,10S,13S,16S)-7-(2-amino-2-oxoethyl)-13-benzyl-10-(cyclohexylmethyl)-16-[(4-hydroxyphenyl)methyl]-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]pyrrolidine-2-carboxamide
• 化学式: C₅₀H₇₁N₁₃O₁₁S₂
• 分子量: 1094.33
• InChiKey: ZKYCVZNKBXGNEK-ZTYVOHGWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  76
• 可旋转键数：
  18
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  445
• 氢给体数：
  12
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  BOC-L-脯氨酸 、 丁氧羰基-L-天冬酰胺对硝苯基酯 、 Boc-S-苄基-L-半光氨酸 、 N-叔丁氧羰基-N'-甲苯磺酰基-L-精氨酸 、 alkaline earth salt of/the/ methylsulfuric acid 生成 [1-deamino-4-cyclohexylalanine][arginine⁸]vasopressin
  参考文献：
  名称：

  Design and Synthesis of the First Selective Agonists for the Rat Vasopressin V_1b Receptor:  Based on Modifications of Deamino-[Cys]arginine Vasopressin at Positions 4 and 8

  摘要：

  The neurohypophyseal peptides arginine vasopressin (AVP) and oxytocin (OT) mediate a wide variety of peripheral and central physiological and behavioral effects by acting on four different G-protein coupled receptors, termed V-1a (vascular), V-1b (pituitary), V-2 (renal), and OT (uterine). We recently reported that d[Cha(4)]AVP (A), d[Leu(4)]AVP (B), d[Orn(4)]AVP (C), and d[Arg(4)]AVP (D) have high affinity and are selective agonists for the human V-1b receptor. However, peptides A-D were subsequently shown to be potent antidiuretic agonists in the rat and are, thus, not selective V-1b agonists in the rat. Peptides A-D served as leads for the studies reported here. They were modified at position 8 by Lys, ornithine (Orn), diaminobutyric acid (Dab), and diaminopropionic acid (Dap) to give d[Cha(4),Lys(8)]VP (1), d[Cha(4),Orn(8)]VP (2), d[Cha(4),Dab(8)]VP (3), d[Cha(4),Dap(8)]VP (4), d[Leu(4),Lys(8)]VP (5), d[Leu(4),Orn(8)]VP (6), d[Leu(4),Dab(8)]VP (7), d[Leu(4),Dap(8)]VP (8), d[Orn(4),Lys(8)]VP (9), d[Orn(4),Orn(8)]VP (10), d[Arg(4),Lys(8)]VP (11), d[Arg(4),Orn(8)]VP (12), and d[Arg(4),Dab(8)]VP (13). All peptides were synthesized by the Merrifield solid-phase method. Their binding and functional properties were evaluated in rat AVP V-1a, V-1b, and V-2 receptors and on the rat OT receptor expressed either in native tissues or in stably transfected cells. They were also examined in rat vasopressor, antidiuretic, and in in vitro (no Mg++) oxytocic assays. Functional studies performed on chinese hamster ovary cells expressing the different AVP/OT receptors confirm that d[Cha(4),Lys(8)]VP (1), d[Cha(4),Dab(8)]VP (3), d[Leu(4),Lys(8)]VP (5), and d[Leu(4),Dap(8)]VP (8) are the first selective agonists for the rat V-1b receptor. These selective V-1b agonists are promising new tools for studies of the role of the V-1b receptor in the rat.

  DOI：

  10.1021/jm060928n

文献信息

• Design and Synthesis of the First Selective Agonists for the Rat Vasopressin V_1b Receptor:  Based on Modifications of Deamino-[Cys]arginine Vasopressin at Positions 4 and 8
  作者：Ana Pena、Brigitte Murat、Miguel Trueba、Maria A. Ventura、Nga C. Wo、Hazel H. Szeto、Ling Ling Cheng、Stoytcho Stoev、Gilles Guillon、Maurice Manning

  DOI：10.1021/jm060928n

  日期：2007.2.1

  The neurohypophyseal peptides arginine vasopressin (AVP) and oxytocin (OT) mediate a wide variety of peripheral and central physiological and behavioral effects by acting on four different G-protein coupled receptors, termed V-1a (vascular), V-1b (pituitary), V-2 (renal), and OT (uterine). We recently reported that d[Cha(4)]AVP (A), d[Leu(4)]AVP (B), d[Orn(4)]AVP (C), and d[Arg(4)]AVP (D) have high affinity and are selective agonists for the human V-1b receptor. However, peptides A-D were subsequently shown to be potent antidiuretic agonists in the rat and are, thus, not selective V-1b agonists in the rat. Peptides A-D served as leads for the studies reported here. They were modified at position 8 by Lys, ornithine (Orn), diaminobutyric acid (Dab), and diaminopropionic acid (Dap) to give d[Cha(4),Lys(8)]VP (1), d[Cha(4),Orn(8)]VP (2), d[Cha(4),Dab(8)]VP (3), d[Cha(4),Dap(8)]VP (4), d[Leu(4),Lys(8)]VP (5), d[Leu(4),Orn(8)]VP (6), d[Leu(4),Dab(8)]VP (7), d[Leu(4),Dap(8)]VP (8), d[Orn(4),Lys(8)]VP (9), d[Orn(4),Orn(8)]VP (10), d[Arg(4),Lys(8)]VP (11), d[Arg(4),Orn(8)]VP (12), and d[Arg(4),Dab(8)]VP (13). All peptides were synthesized by the Merrifield solid-phase method. Their binding and functional properties were evaluated in rat AVP V-1a, V-1b, and V-2 receptors and on the rat OT receptor expressed either in native tissues or in stably transfected cells. They were also examined in rat vasopressor, antidiuretic, and in in vitro (no Mg++) oxytocic assays. Functional studies performed on chinese hamster ovary cells expressing the different AVP/OT receptors confirm that d[Cha(4),Lys(8)]VP (1), d[Cha(4),Dab(8)]VP (3), d[Leu(4),Lys(8)]VP (5), and d[Leu(4),Dap(8)]VP (8) are the first selective agonists for the rat V-1b receptor. These selective V-1b agonists are promising new tools for studies of the role of the V-1b receptor in the rat.