1α,25,26-trihydroxy-16-en-23-yne-vitamin D3 | 343770-67-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 1α,25,26-trihydroxy-16-en-23-yne-vitamin D3
• CAS: 343770-67-2
• 化学式: C₂₇H₃₈O₄
• 分子量: 426.596
• InChiKey: FWQQIUGGZATNRP-SYKGGAEBSA-N

反应信息

• 作为产物：
  描述：

  Ro 23-7553 在 bovine adrenodoxin reductase 、 bovine adrenodoxin 、 recombinant rat cytochrome P450 24A1(Δ2-32) 、 还原型辅酶II(NADPH)四钠盐 作用下， 反应 0.08h， 生成 1α,25,26-trihydroxy-16-en-23-yne-vitamin D3
  参考文献：
  名称：

  A new insight into the role of rat cytochrome P450 24A1 in metabolism of selective analogs of 1α,25-dihydroxyvitamin D3

  摘要：

  We examined the metabolism of two synthetic analogs of 1 alpha,25-dihydroxyvitamin D-3 (1), namely 1 alpha,25-dihydroxy-16-ene-23-yne-vitamin D-3 (2) and 1 alpha,25-dihydroxy-16-ene-23-yne-26,27-dimethyl-vitamin D-3 (4) using rat cytochrome P450 24A1 (CYP24A1) in a reconstituted system. We noted that 2 is metabolized into a single metabolite identified as C26-hydroxy-2 while 4 is metabolized into two metabolites, identified as C26-hydroxy-4 and C26a-hydroxy-4. The structural modification of adding methyl groups to the side chain of 1 as in 4 is also featured in another analog, 1 alpha,25-dihydroxy-22,24-diene-24,26,27-tri-homo-vitamin D-3 (6). In a previous study, 6 was shown to be metabolized exactly like 4, however, the enzyme responsible for its metabolism was found to be not CYP24A1. To gain a better insight into the structural determinants for substrate recognition of different analogs, we performed an in silico docking analysis using the crystal structure of rat CYP24A1 that had been solved for the substrate-free open form. Whereas analogs 2 and 4 docked similar to 1,6 showed altered interactions for both the A-ring and side chain, despite prototypical recognition of the CD-ring. These findings hint that CYP24A1 metabolizes selectively different analogs of 1, based on their ability to generate discrete recognition cues required to close the enzyme and trigger the catalytic mechanism. 2011 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.abb.2011.02.004