【佳學(xué)基因靶向藥物基因檢測】一種從骨碎補(bǔ)中捕獲潛在生物活性化合物的快速方法，利用鈣敏感受體中的疾病相關(guān)突變來改變激動劑的結(jié)合親和力

基因檢測價格關(guān)注的原因

比較基因?qū)嶒?yàn)室人員知識更新明白《J Pharm Biomed Anal》在?2023 Jan 14;226:115253.發(fā)表了一篇題目為《》腫瘤靶向藥物治療基因檢測臨床研究文章。該研究由Kai-Li Meng,?Mei-Zhi Jiao,?Xian-Gang Shi,?Ru Xu,?Pei-Xuan Cheng,?Hui-Ting Lv,?Xiao-Hui Zheng,?Chao-Ni Xiao等完成。促進(jìn)了腫瘤的正確治療與個性化用藥的發(fā)展，進(jìn)一步強(qiáng)調(diào)了基因信息檢測與分析的重要性。

腫瘤基因檢測及靶向藥物治療研究關(guān)鍵詞：

鈣敏感受體 (CaSR),細(xì)胞外結(jié)構(gòu)域 (ECD),鹵化烷烴脫鹵酶（Halo）,骨質(zhì)疏松癥,骨碎補(bǔ) (RD)。

腫瘤治療檢測基因臨床應(yīng)用結(jié)果

骨碎補(bǔ)(RD)因刺激骨形成和抑制骨吸收而被臨床用于治療骨質(zhì)疏松癥，但對骨具有雙重作用的生物活性成分尚不清楚。鈣敏感受體 (CaSR) 中的致病突變可以改變甲狀旁腺激素的分泌，影響骨骼中 Ca2+ 的釋放和腎臟對 Ca2+ 的重吸收，這表明 CaSR 是開發(fā)治療骨質(zhì)疏松癥的潛在靶點(diǎn)。在此，建立了一種色譜方法，通過一步法將突變體 CaSR 固定到硅膠表面作為固定相，然后將不同的氨基酸作為競爭劑添加到流動相中，以探索已知激動劑的結(jié)合特征進(jìn)一步篩選來自RD的配體。突變體CaSR包被柱無需復(fù)雜的受體純化和分離即可快速制備，具有13.1 mg CaSR /g硅膠的大容量，至少35天保持良好的穩(wěn)定性和特異性。 CaSR突變可減弱三種激動劑的結(jié)合親和力，新霉素突變位點(diǎn)Thr151Met、慶大霉素-C突變位點(diǎn)Asn118Lys和Glu191Lys、卡那霉素突變位點(diǎn)Phe612Ser突變位點(diǎn)下降幅度賊大，獲得了新的認(rèn)識進(jìn)入它們的結(jié)構(gòu)-功能關(guān)系。使用突變體 CaSR 涂層柱篩選 RD 中潛在的生物活性化合物，并使用 UPLC-MS 將其識別為香豆酸 4-O-β-D-吡喃葡萄糖苷、咖啡酸和柚皮苷。其中，靶向 CaSR 的柚皮苷可能解釋了 RD 可以控制骨質(zhì)疏松癥。這些結(jié)果表明，這種利用 CaSR 中的疾病相關(guān)突變來改變激動劑結(jié)合親和力的快速、簡單的方法可用于從草藥等復(fù)雜基質(zhì)中有效捕獲潛在的生物活性化合物。關(guān)鍵詞：鈣敏感受體(CaSR);細(xì)胞外結(jié)構(gòu)域 (ECD)；鹵化烷烴脫鹵酶（Halo）；骨質(zhì)疏松癥；骨碎補(bǔ) (RD)。

腫瘤發(fā)生與革命國際數(shù)據(jù)庫描述：

Rhizoma Drynariae (RD) was used clinically to treat osteoporosis in China due to stimulating bone formation and inhibiting bone resorption, however, the bioactive constituents with the dual effect on bone are still unknown exactly. Disease-causing mutations in calcium sensing receptor (CaSR) can alter parathyroid hormone secretion and affect Ca2+?release from bone and Ca2+?reabsorption from kidney, which gives an indication that CaSR is a potential target for developing therapeutics to manage osteoporosis. Herein, a chromatographic approach was established, by immobilizing the mutant CaSR onto the surface of silica gels as stationary phase in a one-step procedure and then adding the different amino acids into mobile phase as competitors, for exploring the binding features of the known agonists and further screening ligands from RD. The mutant CaSR-coated column was prepared rapidly without the complicated purification and separation of the receptor, which had the large capacity of 13.1 mg CaSR /g silica gels and kept a good stability and specificity for at least 35 days. The CaSR mutation can weaken the binding affinities for three agonists, and the largest decreases occurred on the mutational site Thr151Met for neomycin, on the two sites of Asn118Lys and Glu191Lys for gentamicin-C, and on the site Phe612Ser for kanamycin, which gained new insights into their structure-function relationship. The potential bioactive compounds from RD were screened using the mutant CaSR-coated column and were recognized as coumaric acid 4-O-β-D-glucopyranoside, caffeic acid, and naringin using UPLC-MS. Among them, naringin targeting CaSR gives a possible explanation that RD could manage osteoporosis. These results indicated that, such a rapid and simple method, utilizing disease-associated mutation in CaSR to alter the binding affinity for agonists, can be applied in capturing the potential bioactive compounds efficiently from complex matrices like herb medicines.Keywords:?Calcium-Sensing Receptor (CaSR); Extracellular domain (ECD); Halogenated alkane dehalogenase (Halo); Osteoporosis; Rhizoma Drynariae (RD).