英语翻译Bio-orthogonal chemical reactions between two exogenousmoieties in living beings are sought after tools that havepowerful applications in chemical biology,molecular imaging,and medicine.[1–4] The exquisite selectivity of these reactions
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英语翻译Bio-orthogonal chemical reactions between two exogenousmoieties in living beings are sought after tools that havepowerful applications in chemical biology,molecular imaging,and medicine.[1–4] The exquisite selectivity of these reactions
英语翻译
Bio-orthogonal chemical reactions between two exogenous
moieties in living beings are sought after tools that have
powerful applications in chemical biology,molecular imaging,
and medicine.[1–4] The exquisite selectivity of these reactions—
the Staudinger ligation and the strain-promoted azidealkyne
cycloaddition—has been exploited for the metabolic
labeling and subsequent tagging and visualization of biomolecules
in mice by using ex vivo detection,[1–3] and in live
zebrafish embryos.[4] However,the reaction kinetics (k2\2 7.6 \2 10\32m\31 s\31) have required a high dose and large excess
of secondary reagent to achieve detectable binding.Applications
in molecular imaging and medicine that require low
doses and semi-equimolar conditions have therefore
remained unrealized.Reactions that retain selectivity but
have faster kinetics could extend in vivo chemistry to
clinically relevant procedures in mammalian disease models,
by allowing the intravenous administration of a small amount
of probe to non-invasively delineate low-abundance species.
The rapid blood clearance and excretion typical of most small
to medium-sized molecules necessitates that the reaction
occurs within minutes.Such
selectivity and effective equimolar
reactivity has never
been demonstrated in a living
animal.
英语翻译Bio-orthogonal chemical reactions between two exogenousmoieties in living beings are sought after tools that havepowerful applications in chemical biology,molecular imaging,and medicine.[1–4] The exquisite selectivity of these reactions
在生物中两个外源性分子部分之间的生物正交化学反应是寻求的工具,它们在化学生物学、分子成像和医学上有着强有力的应用[1-4].这些化学反应(Staudinger 络合物形成反应和叠氮-炔环加成)精细的选择性已经研究用于以体外检测法进行老鼠中生物分子的代谢标记和其后的标记与造影[1-3],以及用于斑马鱼胚胎的研究[4].可是,其反应动力学(k2≤7.6×10-2M-1 S-1)一直要求大的剂量和大大过量的次要试剂来达到可检测的结合.因此要求低剂量和半等摩尔条件的分子成像和医学上的应用仍然没有实现.保持选择性而具有较快动力学的反应可以通过静脉注射少量探针(probe)而非侵害性地描绘低丰度基因(species)而将体内化学扩展到哺乳动物疾病模型中与临床有关的程序.大多数小到中等大小分子所典型的迅速的血液清除率和排泄要求反应发生在几分钟之内.这样的选择性和有效等摩尔反应性在活的动物身上还从没有实验证实过.