Activity‐Based Protein Profiling: Recent Advances in Probe Development and Applications

The completion of the human genome sequencing project has provided a wealth of new information regarding the genomic blueprint of the cell. Although, to date, there are roughly 20 000 genes in the human genome, the functions of only a handful of proteins are clear. The major challenge lies in translating genomic information into an understanding of their cellular functions. The recently developed activity‐based protein profiling (ABPP) is an unconventional approach that is complementary for gene expression analysis and an ideal utensil in decoding this overflow of genomic information. This approach makes use of synthetic small molecules that covalently modify a set of related proteins and subsequently facilitates identification of the target protein, enabling rapid biochemical analysis and inhibitor discovery. This tutorial review introduces recent advances in the field of ABPP and its applications.     

N-Terminal Modification of Gly-His-Tagged Proteins with Azidogluconolactone

Site-specific protein modifications are vital for biopharmaceutical drug development. Gluconoylation is a non-enzymatic, post-translational modification of N-terminal HisTags. We report high-yield, site-selective in vitro α-aminoacylation of peptides, glycoproteins, antibodies, and virus-like particles (VLPs) with azidogluconolactone at pH 7.5 in 1 h. Conjugates slowly hydrolyse, but diol-masking with borate esters inhibits reversibility. In an example, we multimerise azidogluconoylated SARS-CoV-2 receptor-binding domain (RBD) onto VLPs via click-chemistry, to give a COVID-19 vaccine. Compared to yeast antigen, HEK-derived RBD was immunologically superior, likely due to observed differences in glycosylation. We show the benefits of ordered over randomly oriented multimeric antigen display, by demonstrating single-shot seroconversion and best virus-neutralizing antibodies. Azidogluconoylation is simple, fast and robust chemistry, and should accelerate research and development.     

Chemical Modification of Fiber-forming Polymers Based on Recombination Addition Reactions

Abstract

The essence of chemical modification processes of fiber-forming polymers based on recombination addition reactions involves preliminary sorption of low-molecular components by the fiber being in a high elasticity state with the subsequent transfer of interacting substances into a free radical state as a result of chemical or radiation initiation. Recombination of activated parts then leads to the fixation of a low-molecular component in a polymer matrix.

Various versions of these reactions based on modifications of fibrillar proteins (fibroin and keratin). polyamides. cellulose and its esters, polyvinyl alcohol with ionogenic (cationic and anionic) and non-ionogenic (disperse) dyes of different classes have been considered.     

酶化学修饰的研究进展

化学修饰已成为改进酶的物理化学性能、提高其生物活性的有效方法。着重介绍化学修饰酶的研究与进展,主要内容包括小分子修饰、定点突变和化学修饰结合技术、辅因子引入。综述了各种化学修饰方法的原理。     

Advances and Opportunities in Epigenetic Chemical Biology

The study of epigenetics has greatly benefited from the development and application of various chemical biology approaches. In this review, we highlight the key targets for modulation and recent methods developed to enact such modulation. We discuss various chemical biology techniques to study DNA methylation and the post-translational modification of histones as well as their effect on gene expression. Additionally, we address the wealth of protein synthesis approaches to yield histones and nucleosomes bearing epigenetic modifications. Throughout, we highlight targets that present opportunities for the chemical biology community, as well as exciting new approaches that will provide additional insight into the roles of epigenetic marks.     

蛋白质化学修饰的研究进展

蛋白质分子具有极其复杂的结构层次，用化学修饰的方法研究蛋白质分子的结构与功能的关系一直是生物化学和分子生物学领域的热点。人们研究出许多小分子化学修饰剂并进行了多种类型的化学修饰。综述了蛋白质化学修饰领域的研究现状与水平，同时强调蛋白质的化学修饰是生化药物研究开发的重要手段之一。     

Native Chemical Ligation Combined with Desulfurization and Deselenization: A General Strategy for Chemical Protein Synthesis

Of the many approaches proposed to generalize the native chemical ligation approach for protein synthesis, the simple procedure of global desulfurization of peptide thiols has become the most widely adopted. In this review, the development of the native ligation–desulfurization strategy is described, focusing on the conversion of Cys to Ala following ligation at N-terminal Cys residues. Subsequent variations on this theme have broadened the scope to other natural amino acids including Phe, Leu, Val, and Lys, and even non-native peptide linkages such as isopeptide bonds on lysine side chains. Using insights from both selenocysteine–peptide side reactions and radical initiated desulfurization procedures, a new method for the selective deselenization of peptides containing both selenocysteine and cysteine residues has been developed. Together, these approaches represent a robust and flexible methodology for the synthesis of complex polypeptides without the use of protecting groups.     

介孔材料化学改性研究进展

综述了介孔材料化学改性目的，改性原理以及改性方法。介孔材料的化学改性包括对材料骨架的修饰以及对孔道表面的功能化，介孔材料表面自由硅醇键、双羟基硅醇踺是化学改性的基础，利用疏水性物质改性可以提高材料的水热稳定性，引入催化活性组分可以提高催化性能，利用具有特定官能团的硅烷偶连剂改性，则能够实现特殊的目的。详述了化学改性方法，包括元素取代法、共价键移植法和有机硅烷偶连法。元素取代法是对分子筛骨架结构的修饰，共价键移植法是一种不引起孔道结构破坏且非常有效的骨架修饰方法，对介孔材料表面进行有机硅烷偶连剂法修饰改性主要有两种途径：即共沉淀法和后移植法。     

Chemical Synthesis of Integral Membrane Proteins: Methods and Applications

The development of efficient chemical methods for total synthesis or semisynthesis of integral membrane proteins is an important challenge at the interface between chemistry and biology. This review outlines the recent advances in the synthesis of integral membrane proteins, with particular focus on the methods for difficult peptide synthesis, purification, and enhancement of peptide solubility under the ligation conditions. The applications of these methods to the synthesis of integral membrane proteins with one or multiple transmembrane domains are also described.     

化工技术对合成柴油开发新进展的影响

随着石油资源日益枯竭,寻找优质、廉价的石油代用品是化工行业生存和发展的关键。生物质是化工合成最有希望的石油替代原料之一。介绍了化工及相关技术的新发展,论述了化工与生物、材料、能源、环境等学科的交叉,浅析了化工技术对合成柴油开发新进展的影响,介绍了某些合成柴油的反应机理和工艺。     

Probing Site-Selective Conjugation Chemistries for the Construction of Homogeneous Synthetic Glycodendriproteins

Methods that site-selectively attach multivalent carbohydrate moieties to proteins can be used to generate homogeneous glycodendriproteins as synthetic functional mimics of glycoproteins. Here, we study aspects of the scope and limitations of some common bioconjugation techniques that can give access to well-defined glycodendriproteins. A diverse reactive platform was designed via use of thiol-Michael-type additions, thiol-ene reactions, and Cu(I)-mediated azide-alkyne cycloadditions from recombinant proteins containing the non-canonical amino acids dehydroalanine, homoallylglycine, homopropargylglycine, and azidohomoalanine.     

木榄属植物的化学成分研究进展

从木榄属植物海莲、尖瓣海莲、柱果木榄中分离获得的化学成分主要有二萜、三萜、酚类、含硫化合物、生物碱类化合物等。其中一些化学成分显示了抗肿瘤等药理活性。本研究就近几十年来这几种木榄属植物的化学成分研究进行综述。     

Chemical Protein Modification through Cysteine

The modification of proteins with non‐protein entities is important for a wealth of applications, and methods for chemically modifying proteins attract considerable attention. Generally, modification is desired at a single site to maintain homogeneity and to minimise loss of function. Though protein modification can be achieved by targeting some natural amino acid side chains, this often leads to ill‐defined and randomly modified proteins. Amongst the natural amino acids, cysteine combines advantageous properties contributing to its suitability for site‐selective modification, including a unique nucleophilicity, and a low natural abundance—both allowing chemo‐ and regioselectivity. Native cysteine residues can be targeted, or Cys can be introduced at a desired site in a protein by means of reliable genetic engineering techniques. This review on chemical protein modification through cysteine should appeal to those interested in modifying proteins for a range of applications.     

Metabolic Remodeling of Cell‐Surface Sialic Acids: Principles,Applications, and Recent Advances

Cell‐surface sialic acids are essential in mediating a variety of physiological and pathological processes. Sialic acid chemistry and biology remain challenging to investigate, demanding new tools for probing sialylation in living systems. The metabolic glycan labeling (MGL) strategy has emerged as an invaluable chemical biology tool that enables metabolic installation of useful functionalities into cell‐surface sialoglycans by “hijacking” the sialic acid biosynthetic pathway. Here we review the principles of MGL and its applications in study and manipulation of sialic acid function, with an emphasis on recent advances.     

Efficient Generation of Hydrazides in Proteins by RadA Split Intein

Protein C-terminal hydrazides are useful for bioconjugation and construction of proteins from multiple fragments through native chemical ligation. To generate C-terminal hydrazides in proteins, an efficient intein-based preparation method has been developed by using thiols and hydrazine to accelerate the formation of the transient thioester intermediate and subsequent hydrazinolysis. This approach not only increases the yield, but also improves biocompatibility. The scope of the method has been expanded by employing Pyrococcus horikoshii RadA split intein, which can accommodate a broad range of extein residues before the site of cleavage. The use of split RadA minimizes premature intein N cleavage in vivo and offers control over the initiation of the intein N cleavage reaction. It is expected that this versatile preparation method will expand the utilization of protein C-terminal hydrazides in protein preparation and modification.     

Recent Advances in Magic-Angle Spinning Solid-State NMR of Proteins

Magic-angle spinning (MAS) solid-state NMR (SSNMR) spectroscopy is emerging as an important technique for the determination of three-dimensional structures of biological molecules and for the characterization of their dynamics. While there is an established suite of MAS SSNMR experiments for protein structure determination in small- and medium-sized proteins, these methods face many challenges in large systems. In this review, recent progress in MAS NMR spectroscopy is discussed, specifically focusing on the emerging developments aimed at improving the sensitivity and resolution of SSNMR that are likely to determine its future applications. These developments include sample preparation and isotopic labeling strategies, fast MAS, proton detection, and paramagnetic NMR spectroscopy.     

国外化工塔器的若干最新进展

生产装置的大型化和高新技术的发展对化工塔器提出了更高的要求，激烈的竞争促进了化工塔器的迅速发展。近年来，优化匹配引起了广泛的关注，实验研究和计算机模拟相结合使化工塔器的节能技术迈上了一个新的台阶。