Bioorthogonal Reactions in Animals

The advent of bioorthogonal chemistry has led to the development of powerful chemical tools that enable increasingly ambitious applications. In particular, these tools have made it possible to achieve what is considered to be the holy grail of many researchers involved in chemical biology: to perform unnatural chemical reactions within living organisms. In this minireview, we present an update of bioorthogonal reactions that have been carried out in animals for various applications. We outline the advances made in the understanding of fundamental biological processes, and the development of innovative imaging and therapeutic strategies using bioorthogonal chemistry.     

Bioorthogonal Chemistry in Translational Research: Advances and Opportunities

Bioorthogonal chemistry is a rapidly expanding field of research that involves the use of small molecules that can react selectively with biomolecules in living cells and organisms, without causing any harm or interference with native biochemical processes. It has made significant contributions to the field of biology and medicine by enabling selective labeling, imaging, drug targeting, and manipulation of bio-macromolecules in living systems. This approach offers numerous advantages over traditional chemistry-based methods, including high specificity, compatibility with biological systems, and minimal interference with biological processes. In this review, we provide an overview of the recent advancements in bioorthogonal chemistry and their current and potential applications in translational research. We present an update on this innovative chemical approach that has been utilized in cells and living systems during the last five years for biomedical applications. We also highlight the nucleic acid-templated synthesis of small molecules by using bioorthogonal chemistry. Overall, bioorthogonal chemistry provides a powerful toolset for studying and manipulating complex biological systems, and holds great potential for advancing translational research.     

Identification of the Catalytic Residues in the Cyclase Domain of the Class IV Lanthipeptide Synthetase SgbL

Lanthipeptides belong to the family of ribosomally synthesized and post-translationally modified peptides (RiPPs) and are subdivided into different classes based on their processing enzymes. The three-domain class IV lanthipeptide synthetases (LanL enzymes) consist of N-terminal lyase, central kinase, and C-terminal cyclase domains. While the catalytic residues of the kinase domains (mediating ATP-dependent Ser/Thr phosphorylations) and the lyase domains (carrying out subsequent phosphoserine/phosphothreonine (pSer/pThr) eliminations to yield dehydroalanine/dehydrobutyrine (Dha/Dhb) residues) have been characterized previously, such studies are missing for LanL cyclase domains. To close this gap of knowledge, this study reports on the identification and validation of the catalytic residues in the cyclase domain of the class IV lanthipeptide synthetase SgbL, which facilitate the nucleophilic attacks by Cys thiols on Dha/Dhb residues for the formation of β-thioether crosslinks.     

2,4-二羟基苯甲醛的选择性烷基化研究进展

2,4-二羟基苯甲醛是合成Salen催化剂的一种重要的配体,而烷基化不仅是改变这种配体的一种重要手段,而且还是将这种配体进行高分子化的重要方法。所以本文综述了2,4-二羟基苯甲醛的选择性烷基化的一些研究新进展,以期为合成新型Salen催化剂配体奠定理论基础。     

Switchable Fluorescence of Doxorubicin for Label-Free Imaging of Bioorthogonal Drug Release

Monitoring the release and activation of prodrug formulations provides essential information about the outcome of a therapy. While the prodrug delivery can be confirmed by using different imaging techniques, confirming the release of active payload by using imaging is a challenge. Here, we have discovered that the switchable fluorescence of doxorubicin can validate drug release upon its uncaging reaction with a highly specific chemical partner. We have observed that the conjugation of doxorubicin with a trans-cyclooctene (TCO) diminishes its fluorescence at 595 nm. This quenched fluorescence of the doxorubicin prodrug is recovered upon its bond-cleaving reaction with tetrazine. Clinically assessed iron oxide nanoparticles were used to formulate a doxorubicin nanodrug. The release of doxorubicin from the nanodrug was studied under various experimental conditions. A fivefold increase in doxorubicin fluorescence is observed after complete release. The studies were carried out in vitro in MDA-MB-231 breast cancer cells. An increase in Dox signal was observed upon tetrazine administration. This switchable fluorescence mechanism of Dox could be employed for fundamental studies, that is, the reactivity of various tetrazine and TCO linker types under different experimental conditions. In addition, the system could be instrumental for translational research where the release and activation of doxorubicin prodrug payloads can be monitored by using optical imaging systems.     

Use of Methionine Alkylation to Prepare Cationic and Zwitterionic Block Copolypeptide Vesicles

We have developed a facile method for preparation of ionic copolypeptide vesicles that requires no protecting groups or expensive components. We prepared amphiphilic copolypeptides containing segments of water-soluble methionine sulfonium residues. These were derived by aqueous phase, direct alkylation of a fully hydrophobic precursor diblock copolypeptide, poly(L-methionine)₆₅-block-poly(L-leucine_0.5-stat-L-phenylalanine_0.5)₂₀ (M₆₅[L_0.5/F_0.5]₂₀), with simple alkylating reagents. Methylation of M₆₅(L_0.5/F_0.5)₂₀ gave the cationic methyl-methionine sulfonium derivative M^M₆₅(L_0.5/F_0.5)₂₀, and carboxymethylation gave the zwitterionic carboxymethyl-methionine sulfonium derivative M^C₆₅(L_0.5/F_0.5)₂₀. Assembly of M^M₆₅(L_0.5/F_0.5)₂₀ or M^C₆₅(L_0.5/F_0.5)₂₀ in water gave rise to vesicles with average diameters of a few microns, which could then be extruded to nanoscale diameters. While the cationic M^M-based vesicles were found to be cytotoxic, the zwitterionic M^C-based vesicles were found to possess minimal cytotoxicity.     

Specific Modulation of Protein Activity by Using a Bioorthogonal Reaction

Unnatural amino acids with bioorthogonal reactive groups have the potential to provide a rapid and specific mechanism for covalently inhibiting a protein of interest. Here, we use mutagenesis to insert an unnatural amino acid containing an azide group (Z) into the target protein at positions such that a “click” reaction with an alkyne modulator (X) will alter the function of the protein. This bioorthogonally reactive pair can engender specificity of X for the Z‐containing protein, even if the target is otherwise identical to another protein, allowing for rapid target validation in living cells. We demonstrate our method using inhibition of the Escherichia coli enzyme aminoacyl transferase by both active‐site occlusion and allosteric mechanisms. We have termed this a “clickable magic bullet” strategy, and it should be generally applicable to studying the effects of protein inhibition, within the limits of unnatural amino acid mutagenesis.     

烷基化技术进展

为减少汽车尾气对环境的污染,环保法日益严格,各国对清洁能源的需求更加迫切,清洁燃料的生产成了炼油厂的重中之重,因烷基化油具有良好的性能使其得到很大重视,烷基化技术也因此得到了很大程度的开发。烷基化油是一种具有低蒸汽压、不含烯烃及芳烃等有害杂质的理想汽油高辛烷值调和组分。目前,烷基化技术包括液体酸烷基化法及固体酸烷基化法。其中,液体酸烷基化法又分为氢氟酸法、硫酸法、离子液体法等。介绍了Stratco、Exxon Mobil、UOP、Phillips、Kellogg等世界几大公司的烷基化技术;同时对国内采用上述部分技术投建的装置情况也做了简单介绍;分析概括了一些新型烷基化技术的利用和发展情况;强调了固体酸烷基化技术的优势;最后对中国石油的发展提出了建议。     

Coordination‐Assisted Bioorthogonal Chemistry: Orthogonal Tetrazine Ligation with Vinylboronic Acid and a Strained Alkene

Bioorthogonal chemistry can be used for the selective modification of biomolecules without interfering with any other functionality that might be present. Recent developments in the field include orthogonal bioorthogonal reactions to modify multiple biomolecules simultaneously. During our research, we observed that the reaction rates for the bioorthogonal inverse‐electron‐demand Diels–Alder (iEDDA) reactions between nonstrained vinylboronic acids (VBAs) and dipyridyl‐s‐tetrazines were exceptionally higher than those between VBAs and tetrazines bearing a methyl or phenyl substituent. As VBAs are mild Lewis acids, we hypothesised that coordination of the pyridyl nitrogen atom to the boronic acid promoted tetrazine ligation. Herein, we explore the molecular basis and scope of VBA–tetrazine ligation in more detail and benefit from its unique reactivity in the simultaneous orthogonal tetrazine labelling of two proteins modified with VBA and norbornene, a widely used strained alkene. We further show that the two orthogonal iEDDA reactions can be performed in living cells by labelling the proteasome by using a nonselective probe equipped with a VBA and a subunit‐selective VBA bearing a norbornene moiety.     

全球蛋氨酸市场现状分析

目前全球蛋氨酸市场由少数几家公司控制 ,其中Novus、Degussa、Adiesso公司分别占有 3 4%、3 0 %和 2 8%的市场份额 ,国内迄今尚未有一套规模型生产装置。而亚洲地区蛋氨酸供应紧张 ,中国作为世界第二大饲料生产国 ,对蛋氨酸的需求更高 ,目前我国主要依靠进口解决需求问题 ,2 0 0 1～ 2 0 0 3年每年进口量均在 5万t/a以上。     

Ruthenium‐Catalyzed Synthesis of Secondary Alkylamines: Selective Alkylation with Aliphatic Amines

The chemoselective N‐alkylation of tert‐alkylamines applying aliphatic amines is described for the first time. In the presence of the Shvo catalyst 1 , tert‐octylamine 4 and 1‐adamantylamine 5 are alkylated using primary, secondary, and even tertiary amines to give the corresponding monoalkylated tert‐alkylamine in moderate to very good yields and excellent selectivity. This novel reaction proceeds without an additional hydrogen source and ammonia is formed as the only by‐product.     

季铵盐离子液体催化苯胺选择性烷基化反应

对离子液体介质中苯胺与卤代烃的N-单烷基化反应,考察了9种不同结构的季铵盐、季鏻盐对反应的影响。结果表明,在60℃,用四丁基氯化铵作催化剂、三乙胺作缚酸剂,n(三乙胺)∶n(苯胺)∶n(卤代烃)∶n(四丁基氯化铵)=2∶1∶1∶0.05,苯胺能快速有效地与卤代烃发生N-烷基化反应,高选择性制备仲胺化合物,苯胺转化率达到86%,仲胺选择性达到87%,通过简单的乙醚萃取就可实现产物分离。季铵盐离子液体对邻位或对位有取代基的苯胺烷基化反应,也具有高的苯胺转化率和仲胺选择性,可以代替咪唑鎓盐离子液体用于苯胺选择性单烷基化反应。     

硫酸烷基化技术进展

介绍了硫酸烷基化技术的最新进展,针对硫酸烷基化技术的特点,对不同的酸烃混和技术进行了详细地阐述,为硫酸烷基化工艺的改进及发展提供了参考。     

聚四氟乙烯修饰的MCM-49分子筛上苯与丙烯烷基化反应

制备了MCM-49分子筛负载25％聚四氟乙烯催化剂,将催化剂应用于苯与丙烯烷基化反应.结果表明,反应温度＜150℃时,表面疏油性催化剂可以使反应中由丙烯聚合生成的油性大分子和多异丙苯较快的从催化剂表面脱附,减少了油性大分子对催化剂活性中心的覆盖,减少积炭生成,提高了催化剂寿命.     

离子液体在烷基化反应中的应用

离子液体作为一种环境友好的催化剂和溶剂,受到了人们日益的关注。本文介绍了离子液体独特的性质,重点对离子液体在催化烯烃烷基化制高辛烷值烷基化汽油、苯与烯烃的烷基化制烷基苯,苯与卤代烷烃的烷基化以及萘、酚的烷基化反应中的应用进行综述。在这些反应中,离子液体不仅表现出良好的催化活性和选择性,同时具有产品易分离,催化剂可以循环使用,环境污染小和设备腐蚀不严重等优点。     

间接烷基化技术进展

异丁烯叠合-加氢可获得高辛烷值的异辛烷,是生产烷基化油的新途径,被称为间接烷基化技术。本文介绍了这一技术的催化剂、工艺以及工业化过程的新进展。国内外的发展状况表明,间接烷基化技术已趋成熟,将在清洁汽油的生产中发挥重要作用。     

超顺磁核-壳结构催化剂在裂化汽油烷基化脱硫中的应用

通过可控液相沉积制备具有超顺磁性能的介孔核-壳结构Fe₃O₄@nSiO₂@mSiO₂-Al₂O₃和H₃P₁₂W40/Fe₃O₄@nSiO₂@mSiO₂-Al₂O₃催化剂。以噻吩和异戊烯组成的模拟汽油烷基化反应作为探针反应,考察催化脱硫性能,并采用FT-IR、N2等温吸附-脱附、NH₃-TPD、VSM和SEM等方法对催化剂进行表征。结果表明,Fe₃O₄@nSiO₂@mSiO₂-Al₂O₃催化剂是具有超顺磁性和介孔结构特征的固体酸催化剂,其饱和磁化强度为46.3 emu·g^-1,低矫顽力为零,比表面积为342.6 m²·g^-1。模拟汽油在Fe₃O₄@nSiO₂@mSiO₂-Al₂O₃催化剂上170 ℃反应2 h,噻吩转化率为72.2%,负载质量分数40%的磷钨酸后,噻吩转化率达96.9%,催化活性、选择性和催化剂寿命均提高。     

固载化AlCl_3催化剂上萘与丙烯的烷基化反应

采用两步气相法制备了AlCl_3/Naβ、AlCl_3/SiO_2、AlCl_3/NaMCM-41和AlCl_3/NaY固载AlCl_3催化剂,并考察其在萘和丙烯烷基化反应中的催化性能。通过N_2吸附、傅立叶变换红外光谱及化学分析法表征了载体的物化性能及催化剂表面酸性。结果表明,AlCl_3固载化作用对载体的比表面积、孔容和孔径大小具有较大影响,且催化剂孔道结构影响萘烷基化反应活性和选择性。以Naβ为载体制备的AlCl_3/Naβ催化剂具有较高的萘与丙烯的烷基化反应活性,在反应温度85℃、反应时间5 h和常压条件下,萘转化率为77.63%,n(2,6-二异丙基萘):n(2,7-二异丙基萘)达到1.02。