Profile of ligand specificity of the vitamin D binding protein for 1α,25‐dihydroxyvitamin d3 and its analogs
Profile of ligand specificity of the vitamin D binding protein for 1α,25‐dihydroxyvitamin d3 and its analogs
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维生素 D 结合蛋白对 1α,25-二羟基维生素 d3 及其类似物的配体特异性概况
DOI：
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发表时间：
1994
影响因子：
6.2
通讯作者：
A. Norman
中科院分区：
文献类型：
--
作者：
J. Bishop;E. D. Collins;W. Okamura;A. Norman
通过71个1-α，25-二羟基维生素D3[1α，25(OH)2D3]类似物的类固醇竞争分析，确定了人维生素D结合蛋白配体结合域的结构偏好。评价了下列类别的结构修饰[数值代表折叠变化；R=还原，I=从参考文献1α，25(OH)2D3与DBP结合的增加]：(1)A环中1α-羟基的缺失(20-1600I)；(2)三烯体系转化为前维他命形式(6-40R)；(3)C环的碳11上加取代基(4-14R)；(4)C/D环结的反转(8-20R)；(5)D环的不饱和(16-En；(4-140R)；(6)用氢原子取代氢(没有影响)；(7)通过添加或删除碳原子(5-12R)改变侧链；(8)添加氟(0.2-10R)；(9)存在不饱和(22-烯，0-5R；23-烯，3R-10I；23-炔，5-20R)；(10)添加羟基(2-100R)；和(11)加成芳环(0-20I)。因此，DBP配体结合域只能容忍1α，25(OH)2D3结构的轻微变化，而不会减少类似物的结合。在芳香族侧链中看到的结合增加以及在碳-23处的三键可能表明柔性1α，25(OH)2D3侧链的优选构象。此外，还与人HL-60细胞1α，25(OH)2D3核受体的DBP配体结合域进行了比较。这两个配体结合域可以等效地容纳(1)侧链环丙基，(2)22-烯或23-炔，(3)侧链加长两个碳，(4)存在四到六个氟原子，(5)氧取代碳22，和(6)侧链中存在22-[m-(二甲基羟甲基)苯基]芳香基。与HL-60细胞受体相比，DPB能更好地耐受侧链上含有22-(对羟基苯基)芳香基团和不含1-α-羟基的情况。相反，HL-60细胞受体可以比DBP更好地耐受以下结构修饰：存在16-烯或16-烯加23-炔不饱和，以及存在11β-羟基。
The profile of structural preference for the ligand binding domain of the human vitamin D binding protein (DBP) was determined by steroid competition assay of 71 analogs of 1α,25‐dihydroxyvitamin D3 [1α,25(OH)2D3]. The following categories of structural modification were evaluated [values represent fold change; R = reduction, I = increase in binding to the DBP from the reference 1α,25(OH)2D3]: (1) deletion in the A ring of the 1α‐hydroxyl (20‐1600I); (2) conversion of the triene system to the previtamin form (6‐40R); (3) addition of substituents to carbon 11 of the C ring (4‐14R); (4) inversion of the C/D ring junction (8‐20R); (5) unsaturation of the D ring (16‐ene; 4‐140R); (6) replacement of hydrogen with deuterium atoms (no effect); alteration of the side chain by (7) adding or deleting carbon atoms (5‐12R); (8) addition of fluorines (0.2‐10R); (9) presence of unsaturation (22‐ene, 0‐5R; 23‐ene, 3R‐10I; 23‐yne, 5‐20R); (10) addition of hydroxyls (2‐100R); and (11) addition of an aromatic ring (0‐20I). Thus the DBP ligand binding domain could tolerate only modest changes to the structure of 1α,25(OH)2D3 without a reduction in binding of the analog. The increases in binding seen in the aromatic side chain and with a triple bond at carbon‐23 may be indicative of a preferred conformation of the flexible 1α,25(OH)2D3 side chain. In addition, a comparison was made of the DBP ligand binding domain with that of the human HL‐60 cell 1α,25(OH)2D3 nuclear receptor. Both ligand binding domains could equivalently accommodate to the presence of (1) a side‐chain cyclopropyl group, (2) 22‐ene or 23‐yne, (3) lengthening the side chain by two carbons, (4) presence of four to six fluorine atoms, (5) substitution of an oxygen for carbon 22, and (6) presence of a 22‐[m‐(dimethylhydroxymethyl)phenyl] aromatic group in the side chain. The DPB could tolerate better than the HL‐60 cell receptor the presence of a 22‐(p‐hydroxyphenyl) aromatic group in the side chain and the absence of the 1α‐hydroxyl. In contrast, the HL‐60 cell receptor could tolerate better than the DBP the following structural modifications: presence of a 16‐ene, or 16‐ene plus 23‐yne unsaturation, and presence of an 11β‐hydroxyl.
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影响因子：
2.9
作者：
HADDAD, JG;HU, YZ;COOKE, NE
通讯作者：
COOKE, NE
影响因子：
5.8
作者：
BIKLE, DD;GEE, E;HADDAD, JG
通讯作者：
HADDAD, JG
新型维生素 D 类似物可调节白血病细胞生长和分化，对肠道钙吸收或骨动员几乎没有影响。
影响因子：
20.3
作者：
Zhou,JY;Norman,AW;Lübbert,M;Collins,ED;Uskokovic,MR;Koeffler,HP
通讯作者：
Koeffler,HP
开发一种新型 1,25(OH)2-维生素 D3 类似物，具有诱导 HL-60 细胞分化而不调节钙代谢的强大能力。
影响因子：
20.3
作者：
Zhou,JY;Norman,AW;Akashi,M;Chen,DL;Uskokovic,MR;Aurrecoechea,JM;Dauben,WG;Okamura,WH;Koeffler,HP
通讯作者：
Koeffler,HP
与肠/T47D 细胞相同的单一受体介导 HL-60 细胞中 1,25-二羟基维生素 D-3 的作用。
DOI：
10.1016/0167-4781(92)90063-6
发表时间：
1992
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Goto,H;Chen,KS;Prahl,JM;DeLuca,HF
通讯作者：
DeLuca,HF