神经激肽A(4-10) | 97559-35-8

• 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
• 中文名称: 神经激肽A(4-10)
• 中文别名: 神经激肽A
• 英文名称: Asp-Ser-Phe-Val-Gly-Leu-Met-NH2
• 英文别名: neurokinin A(4-10)；(3S)-3-amino-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-4-oxobutanoic acid
• CAS: 97559-35-8
• 化学式: C₃₄H₅₄N₈O₁₀S
• 分子量: 766.916
• InChiKey: YLVSTHFZZCHRCL-ORUZXOCWSA-N

物化性质

• 沸点：
  1231.2±65.0 °C(Predicted)
• 密度：
  1.276±0.06 g/cm3(Predicted)
• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  -3
• 重原子数：
  53
• 可旋转键数：
  24
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  327
• 氢给体数：
  10
• 氢受体数：
  12

制备方法与用途

生物活性

Neurokinin A (4-10) 是速激肽 NK2 受体激动剂。

靶点

NK2受体

体外研究

神经激肽 A (NKA) 和其截短形式 NKA(4-10) 是人类结肠环肌的强大收缩刺激物，这一作用是通过 tachykinin NK2 受体介导的。对神经激肽 A (NKA) 片段 NKA(4-10) 的结构-活性研究旨在探讨氨基酸残基对于 NK2 受体在人类结肠环肌中的效能、效力和亲和力的重要性。该组织中 NK2 受体的高度密度已被通过体外放射自显影和放射配体结合方法证实。

反应信息

• 作为产物：
  描述：

  BOC-甘氨酸 、 N-Boc-L-缬氨酸 、 BOC-L-亮氨酸 、 Boc-L-蛋氨酸 、 alkaline earth salt of/the/ methylsulfuric acid 生成 神经激肽A(4-10)
  参考文献：
  名称：

  A new class of high affinity ligands for the neurokinin A NK2 receptor: .psi.(CH2NR) reduced peptide bond analogs of neurokinin A4-10

  摘要：

  Analogues of [Leu10]NKA4-10 were synthesized in which each of the amide bonds was sequentially replaced with the reduced amide psi(CH2NH) bond to determine the effect of this structural modification on the antagonism of NKA binding to the HUB NK2 receptor. [psi(CH2-NH)9,Leu10]NKA4-10 (6) retained significant affinity for the NK2 receptor (IC50=115 nM) and showed weak partial stimulation of PI turnover (approximately 10-15% of NKA maximum). 6 behaves as a competitive antagonist of NKA-stimulated PI turnover with a pA2=6.7. The secondary amine of the psi(CH2NH) moiety of 6 was converted to a tertiary amine by alkylation. This modification was found to have a small effect upon receptor affinity but did result in attenuation of partial agonist activity. A combination of amino acid substitutions and psi(CH2NH) alkylation yielded [betaAla8,psi(CH2N(CH2)2CH3)9,Phe10]NKA4-10 (21) which has very high affinity for the HUB NK2 receptor. This compound inhibited [I-125]NKA binding with an IC50=1 nM which is equal to the receptor affinity of NKA. Compound 21 also shows very weak partial agonism of PI turnover (less-than-or-equal-to 5% of NKA maximum) which makes this the most potent member of a new class of NKA ligands: psi(CH2NR)9-NKA4-10 analogues which potently antagonize NKA binding and possess minimal partial agonist activity.

  DOI：

  10.1021/jm00099a024