Design of drugs for Vitamin D receptor mutant related to hereditary vitamin D-resistant rickets

遗传性维生素D抵抗性佝偻病相关维生素D受体突变体的药物设计

• 批准号: 15590107
• 负责人: KURIHARA Masaaki
• 金额: $ 2.3万
• 依托单位: National Institute of Health Sciences
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590107/
• 关键词: vitamin D_3 analogues; hereditary vitamin D-resistant rickets; vitamin D receptor; コンピュータモデリング

Hereditary vitamin D-resistant rickets(HVDRR) is a genetic disorder caused by mutations in the vitamin D receptor, which lead to resistance to 1a,25-dihydroxyvitamin D_3[1a,25(OH)_2D_3]. We found that the A ring-modified analogues, 2a-(3-hydroxypropyl)- and 2a-(3-hydroxypropoxy)- 1a,25(OH)_2D_3, (O1C3 and O2C3) can bind better than the natural hormone to the mutant VDR (R274A), which similar to the HVDRR mutant, R274L, had lost the hydrogen bond to the 1a-hydroxyl group of 1a,25(OH)_2D_3,.

遗传性维生素D抵抗性佝偻病（HereditaryVitamin D-resistant Rickets，HVDRR）是一种由维生素D受体（Vitamin D receptor，VRD）突变引起的遗传性疾病，其受体对1a，25（OH）_2D_3 [1a，25（OH）_2D_3]产生抵抗。我们发现A环修饰的类似物2a-（3-羟丙基）-和2a-（3-羟丙氧基）-1a，25（OH）_2D_3，（O1C_3和O2C_3）能比天然激素更好地与突变体VDR（R274 A）结合，该突变体与HVDRR突变体R274 L相似，失去了与1a，25（OH）_2D_3，（O1C_3和O2C_3）的1a-羟基的氢键。

项目成果

Chiral Centers in the Side Chains of α-Amino Acids Control the Helical Screw Sense of Peptides

α-氨基酸侧链的手性中心控制肽的螺旋方向

• 发表时间: 2004
• 期刊: Angew.Chem.Int.Ed. 43
• 作者: M.Tanaka;Y.Demizu;M.Doi;M.Kurihara;H.Suemune
• 通讯作者: H.Suemune

E.Okada, Y.Komazawa, M.Kurihara, H.Inoue, N.Miyata, H.Okuda, T.Tsuchiya, Y.Yamakoshi: "Synthesis of C_<60> derivative for photoaffinity labeling"Tetrahedron Lett.. 45. 527-529 (2004)

E.Okada、Y.Komazawa、M.Kurihara、H.Inoue、N.Miyata、H.Okuda、T.Tsuchiya、Y.Yamakoshi：“用于光亲和标记的 C_<60> 衍生物的合成”Tetrahedron Lett.. 45。

Computational Study on Conformation of Oligopeptides Containing Chiral alpha, alpha-Disubstituted Amino Acids

含手性α、α-二取代氨基酸寡肽构象的计算研究

• 发表时间: 2003
• 期刊: Peptides 2002
• 作者: M.Kurihara;M.Tanaka;M.Oba;H.Suemune
• 通讯作者: H.Suemune

Design and Efficient Synthesis of 2α-(w-Hydroxyalkoxy)-lα,25-dihydroxyvitamin D_3 Analogues, Including 2-epi-ED-71 and Their 20-Epimers with HL-60 Cell Differentiation

2α-(w-羟基烷氧基)-lα,25-二羟基维生素 D_3 类似物的设计和高效合成，包括 2-epi-ED-71 及其 20-差向异构体与 HL-60 细胞分化

• 发表时间: 2004
• 期刊: J.Org.Chem. 69
• 作者: N.Saito;Y.Suhara;M.Kurihara;T.Fujishima;S.Honzawa;H.Takayanagi;T.Kozono;M.Matsumoto
• 通讯作者: M.Matsumoto

Convenient Preparation of Cyclic Acetals Using Diols, TMS-source and a Catalytic Amount of TMSOTf

使用二醇、TMS 源和催化量的 TMSOTf 方便地制备环状缩醛

• 发表时间: 2003
• 期刊: J.Org.Chem. 68
• 作者: M.Kurihara;W.Hakamata
• 通讯作者: W.Hakamata