Bioorthogonal chemistry provides a true nexus between chemistry and biology, using abiological reactions developed by chemists to create new tools and techniques for biology. These bioorthogonal strategies are particularly relevant to the Bioconjugate Chemistry community, providing new methods to bring together (covalently) the chemical and biological worlds. To celebrate the rapid advances in this field, we have chosen our favorite recent publications in BC in the area of bioorthogonal chemistry, and we hope you find the work as exciting as we do. New bioorthogonal strategies open new avenues for bioconjugation. “Traditional” organic processes such as Diels–Alder(1) and other “click” reactions(2,3) provide reactions truly orthogonal to biology, while tandem(4) and multicomponent(5) reactions can rapidly introduce new diversity to bioconjugation processes. The same holds for ring-opening metathesis, which affords the synthesis of polymers with orthogonal handles.(6) Bioorthogonal chemistry can also incorporate and employ elements such as boron, providing structures and properties that biology cannot access.(7,8) Site specificity is an important goal for bioconjugation, and one where bioorthogonal processes have made important contributions. Enzymatic(9) and affinity-guided tagging(10) provide effective selectivity, while genetic code expansion offers the unique opportunity to incorporate the orthogonal handles during protein biosynthesis.(11) The use of bioorthogonal catalysis coupled with DNA nanostructures is a particularly intriguing new direction to site-selectively modify proteins.(12) Bioorthogonal functionalization is an enabling technology for a broad range of applications. One of the more prominent areas of research is antibody modification,(13) where these strategies provide enhanced properties (e.g., circulation time)(14) and important capabilities such as bispecificity.(15) Enhanced circulation can also be realized with peptides using bioorthogonal modification.(16) These approaches also provide ready functionalization of an array of biologically active materials, including nanoparticles(17) and microbubbles.(18) The fact that bioorthogonal reactions do not interfere with biological processes makes them ideal for use in vitro and in vivo for cell labeling,(3,6) and tagging of exosomes.(19) Novel conjugation chemistries are employed inside cells, providing a new direction for therapeutic(20) and intracellular protein labeling(21) strategies. BC’s focus on the chemistry–biology interface makes clinical translation a key part of its portfolio. Bioorthogonal transformations are being tested preclinically, with much of the current focus on imaging. These strategies work particularly well for pretargeting, where they allow efficient coupling of the targeting and imaging agents at tumor sites to maximize efficacy of radiolabeled agents.(11,14,15,22) As you can see from this Virtual Issue, researchers in bioorthogonal chemistry are moving science forward on many fronts, and BC is right there alongside these interdisciplinary scientists. We hope that you will continue following this work, and send your own contributions in this area to BC—the journal at the biology–chemistry interface. This article references 22 other publications.

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生物正交化学和生物共轭：生物学和生物医学的协同工具

生物正交化学提供了化学和生物学之间的真正联系，使用化学家开发的非生物反应为生物学创造新的工具和技术。这些生物正交策略与生物共轭化学社区特别相关，提供了将化学和生物世界（共价）结合在一起的新方法。为了庆祝该领域的快速发展，我们选择了我们最喜欢的BC近期出版物在生物正交化学领域，我们希望您发现这项工作和我们一样令人兴奋。新的生物正交策略为生物偶联开辟了新的途径。“传统”有机过程，如 Diels-Alder(1) 和其他“点击”反应 (2,3) 提供了真正与生物学正交的反应，而串联 (4) 和多组分 (5) 反应可以迅速为生物偶联过程引入新的多样性. 这同样适用于开环复分解，它提供了具有正交手柄的聚合物的合成。(6) 生物正交化学还可以结合和使用硼等元素，提供生物学无法获得的结构和特性。(7,8) 位点特异性是生物共轭的一个重要目标，也是生物正交过程做出重要贡献的目标。酶促 (9) 和亲和引导标记 (10) 提供了有效的选择性，而遗传密码扩展提供了在蛋白质生物合成过程中整合正交手柄的独特机会。 (11) 使用生物正交催化与 DNA 纳米结构相结合是一种特别有趣的新方法位点选择性修饰蛋白质的方向。(12) 生物正交功能化是一种应用广泛的技术。较突出的研究领域之一是抗体修饰，(13) 这些策略提供了增强的特性（例如，循环时间）(14) 和重要的能力，例如双特异性。 (15) 使用生物正交的肽也可以实现增强的循环(16) 这些方法还提供了一系列生物活性材料的现成功能化，体外和体内细胞标记、(3,6) 和外泌体标记。(19) 细胞内采用了新型偶联化学，为治疗 (20) 和细胞内蛋白质标记 (21) 策略提供了新的方向。BC对化学-生物学界面的关注使临床翻译成为其产品组合的关键部分。生物正交变换正在临床前进行测试，目前主要集中在成像上。这些策略特别适用于预靶向，它们允许在肿瘤部位有效耦合靶向剂和显像剂，以最大限度地提高放射性标记剂的功效。 (11,14,15,22) 正如您从这个虚拟问题中看到的，生物正交研究的研究人员化学在许多方面推动科学向前发展，而BC就在这些跨学科科学家旁边。我们希望你将继续遵循这一工作，并在这一领域发出自己的贡献BC -将在生物学，化学界面杂志。本文引用了 22 篇其他出版物。