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一种检测适配体与配体小分子结合过程中构象改变的方法

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摘要

本发明涉及生物医药技术领域，具体是一种快速有效的检测适配体与配体小分子结合过程中构象改变的方法，包括以下步骤：首先应用生物膜干涉实验确定所选适配体和小分子之间的亲和力大小；然后通过表面增强拉曼散射光谱技术对适配体结合小分子前后发生的构象改变进行检测；最后通过分子动力学模拟直观阐述适配体与配体的结合过程。本发明以茶碱及其适配体为例，验证上述方法对于研究适配体构象改变的可靠性，为设计、修饰、筛选出具有高亲和力、高选择性的适配体提供新方法、新思路，使其更好地应用到检测、传感、临床诊断和治疗等领域中。

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公开/公告号CN110849863B

专利类型发明专利
公开/公告日2020-11-24

原文格式PDF
申请/专利权人中国人民解放军第二军医大学;
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申请/专利号CN201910978373.9
发明设计人陆峰;崔晓林;柳艳;袁一凡;王梁华;柴逸峰;
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申请日2019-10-15
分类号G01N21/65(20060101);
代理机构31268 上海元一成知识产权代理事务所(普通合伙);
代理人孙跃虹
地址 200433 上海市杨浦区翔殷路800号
入库时间 2022-08-23 11:22:55

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1. 一种检测适配体与配体小分子结合过程中构象改变的方法 [P] . 中国专利： CN110849863B . 2020.11.24
2. 一种快速有效的检测适配体与配体小分子结合过程中构象改变的方法 [P] . 中国专利： CN110849863A . 2020-02-28
3. isolated polynucleotide, expression cassette, host cell, isolated polypeptide, non-human transgenic animal that has been altered to express an alkali resistant mutant polypeptide, an antibody that specifically binds to an alkali resistant mutant polypeptide, a mutation detection kit alk inhibitor resistance in a biological sample, and methods for evaluating a biological sample for an alk inhibitor resistance mutation to diagnose cancer that is resistant to or likely to develop resistance to at least one alkaline inhibitor. small alk molecule kinase, to evaluate a biological sample for an alk inhibitor resistance mutation, to diagnose cancer that is resistant to or likely to develop resistance to pf-02341066 in a patient, to specifically reduce expression of an alk-resistant mutant to treat cancer associated with activating aberrant loop capacity that is resistant to at least one small molecule alk kinase inhibitor treating an aberrant cancer that is resistant to pf-02341066, identifyin [P] . BR112012026239A2 . 2018-06-26

机译：分离的多核苷酸，表达盒，宿主细胞，分离的多肽，已被改变以表达耐碱突变体多肽的非人类转基因动物，与耐碱突变体多肽特异性结合的抗体，突变检测试剂盒生物样品，以及用于评估生物样品中是否存在对烷基抑制剂的抗性突变以诊断对至少一种碱性抑制剂有抗药性或可能发展出抗药性的癌症的方法。小分子激酶，用于评估生物学样品中是否具有抑制碱性磷酸酶抑制剂的突变，以诊断对患者具有抗药性或可能对pf-02341066产生抗药性的癌症，从而特异性降低抗癌突变体的表达以治疗癌症与激活抗至少一种小分子烷基激酶抑制剂的异常环路能力有关，该抑制剂治疗对pf-02341066有抵抗力的异常癌症
4. Appropriate methods to typify prpsc and to alter the conformation of prpsc, use of an agent capable of affecting the binding of prpsc to one or more divalent metal ions, methods of screening for an agent capable of altering the conformation of type 1 and / or prpsc type 2 and screening for an agent for use in the diagnostic prevention and / or treatment of prion disease, use of an agent obtainable by a method, kit, type 2 isolated prpsc, and use of type 2 isolated prpsc [P] . BR0009675A . 2002-03-26

机译：表征prpsc和改变prpsc构象的适当方法，使用能够影响prpsc与一种或多种二价金属离子结合的试剂，筛选能够改变1型和/或prpsc构象的试剂的方法类型2和筛选可用于诊断性预防和/或治疗病毒疾病的药物，使用可通过方法，试剂盒获得的药物，2型分离的prpsc和2型分离的prpsc
5. Polinucleotu00eddeo insulated tape of expression, host cell, isolated transgenic non-human animal polypeptide, which has been modified to express a polypeptide mutant with resistance to ALK, antibody that binds specifically to a polypeptide mutant with resistance to ALK, kit p For detection of a mutation with resistance to ALK inhibitor in a biological sample, and,Methods for evaluating a biological sample as a mutation with resistance to ALK inhibitor, for diagnosing a cancer that is resistant to or is likely to develop resistance to at least one inhibitor of kinase small molecule ALK, to evaluate a biological sample that Anto a mutation with resistance to ALK inhibitor.For diagnosing a cancer that is resistant to or is likely to develop resistance to at least one inhibitor of kinase small molecule ALK, to assess the biological sample as a mutation with resistance to ALK inhibitor, a cancer that is resistant to dianosticar Or is likely to develop resistance to PF - 02341066 in a pati [P] . BR112012026239A2 . 2016-11-29

机译：修饰的多聚核苷酸绝缘带，宿主细胞，分离的转基因非人类动物多肽，经过修饰以表达对ALK具有抗性的多肽突变体，与对ALK具有抗性的多肽突变体特异性结合的抗体，试剂盒p用于检测生物样品中对ALK抑制剂具有抗性的突变，以及用于评估生物样品为对ALK抑制剂具有抗性的突变的方法，用于诊断对至少一种对ALK抑制剂具有抗性或可能发展出抗性的癌症激酶小分子ALK，以评估Anto对ALK抑制剂具有抗性的突变的生物样品。用于诊断对至少一种激酶小分子ALK抑制剂具有抗药性或可能产生抗性的癌症，以评估该生物样品作为对ALK抑制剂有抗性的突变，即对狄诺司他抗性或可能对PF产生抗药性的癌症-02341066