MOFzyme: FJU-21 with Intrinsic High Protease-Like Activity for Hydrolysis of Proteins

In this work, metal-organic frameworks (MOFs) FJU-21 was synthesized by solvothermal method. The crystal structure of FJU-21 was characterized by XRD and BET and it was applied to the catalytic hydrolysis of bovine serum albumin. The effects of reaction pH, temperature and reaction time on the catalytic activity of FJU-21 were studied. FJU-21 were found to possess an intrinsic enzyme mimicking activity similar to that found in trypsin. The Michaelis constant (Km) of the artificial protease (0.18 × 10-3 - 0.20 × 10-3 M-1) was about 15-fold lower than that free trypsin (2.7 × 10-3 M-1) and about 3-fold lower than that of soluble Cu(II) oxacyclen (0.54 × 10-3 M-1). The Kcat of FJU-21 is 102 times higher than that of soluble Cu(II) oxacyclen catalysts and, indicating a much higher affinity of BSA for FJU-21 surface. FJU-21 could be reused for eleven times without losing in its activity.

A supramolecular oligo[2]rotaxane constructed by orthogonal platinum(Ⅱ) metallacycle and pillar[5]arene-based host–guest interactions

Oligo[n]rotaxanes are one of the most extensively studied categories of mechanically bonded macromolecules.In this study,a supramolecular oligo[2]rotaxane is successfully constructed driven by platinum(Ⅱ)metallacycle and pillar[5]arene-based host–guest interactions in an orthogonal way.The supramolecular oligo[2]rotaxane is further applied in fabricating a light harvesting system.

An Improved Approach for Rapidly Identifying Different Types of Gram-Negative Bacterial Secreted Proteins

Protein secretion plays an important role in bacterial lifestyles. In Gram-negative bacteria, a wide range of proteins are secreted to modulate the interactions of bacteria with their environments and other bacteria via various secretion systems. These proteins are essential for the virulence of bacteria, so it is crucial to study them for the pathogenesis of diseases and the development of drugs. Using amino acid composition (AAC), position-specific scoring matrix (PSSM) and N-terminal signal peptides, two different substitution models are firstly constructed to transform protein sequences into numerical vectors. Then, based on support vector machine (SVM) and the “one to one”?algorithm, a hybrid multi-classifier named SecretP v.2.2 is proposed to rapidly and accurately?distinguish different types of Gram-negative?bacterial secreted proteins. When performed on the same test set for a comparison with other methods, SecretP v.2.2 gets the highest total sensitivity of 93.60%. A public independent dataset is used to further test the power of SecretP v.2.2 for predicting NCSPs, it also yields satisfactory results.

MOFzyme: Enzyme Mimics of Fe/Fe-MIL-101

In this work, metal-organic frameworks (MOFs) Fe-MIL-101 was synthesized by hydrothermal method, and Fe/Fe-MIL-101 with different loadings was prepared. The crystal structure of the Fe/Fe-MIL-101 sample was characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and specific surface area measurement (BET). Fe/Fe-MIL-101 was found to posses an intrinsic enzyme mimicking activity similar to that found in natural horse-radish peroxidase (HRP). The Michaelis constant (Km) of 5% Fe/Fe-MIL-101 with ABTS as the substrate is about 10-fold smaller than Fe-MIL-101 and about 3-fold smaller than HRP, and about 108 times less than that of CuO NPs (Km = 10.28 mM), indicating a much higher affinity for ABTS than HRP and most of the peroxidase mimetics.

Complex tree: the basic framework of protein-protein interaction networks

In living cells, proteins are dynamically connec ted through biochemical reactions, so its functi onal features are properly encoded into protein protein interaction networks (PINs). Up to pres ent, many efforts have been devoted to exploring the basic feature of PINs. However, it is still a challenging problem to explore a universal pr operty of PINs. Here we employed the complex networks theory to analyze the proteinprotein interactions from Database of Interacting Prot ein. Complex tree: the unique framework of PINs was revealed by three topological properties of the giant component of PINs (GCOP), including rightskewed degree distributions, relatively sm all clustering coefficients and short characteristic path lengths. Furthermore, we proposed a no nlinearly growth model: complex tree model to reflect the tree framework, the simulation resu lts of this model showed that GCOPs were well represented by our model, which could be help ful for understanding the treestructure: basic framework of PINs. Source code and binaries freely available for download at http://cic.scu. edu.cn/bioinformatics/STM/STM_code.rar.

Antimony salt-promoted cyclization facilitating on-DNA syntheses of dihydroquinazolinone derivatives and its applications

DNA-encoded chemical libraries technology has become a novel approach to finding hit compounds in early drug discovery.The chemical space in a DEL would be expanded to realize its full potential,especially when integrating privileged scaffold dihydroquinazoline that has demonstrated a variety of diverse bioactivities.Driven by the requirement of parallel combinatorial synthesis,we here report a facile synthesis of on-DNA dihydroquinazolinone from aldehyde and anthranilamide.This DNA-compatible reaction was promoted by antimony trichloride,which has been proven to accelerate the reaction and improve conversions.Notably,the broad substrate scope of aldehydes and anthranilamides was explored under the mild reaction condition to achieve moderate-to-excellent conversion yields.We further applied the reaction into on-DNA macrocyclization,obtaining macrocycles embedded dihydroquinazolinone scaffold in synthetically useful conversion yields.

Second-generation DNA-encoded multiple display on a constant macrocyclic scaffold enabled by an orthogonal protecting group strategy

DNA-encoded chemical library(DEL)represents an emerging drug discovery technology to construct com-pound libraries with abundant chemical combinations.While drug-like small molecule DELs facilitate the discovery of binders against targets with defined pockets,macrocyclic DELs harboring extended scaffolds enable targeting of the protein–protein interaction(PPI)interface.We previously demonstrated the design of the first-generation DNA-encoded multiple display based on a constant macrocyclic scaffold,which harvested binders against difficult targets such as tumor necrosis factor-α(TNF-α).Here,we developed a novel strategy which utilized four orthogonal amine-protecting groups on DNA,to explore larger chem-ical combinations on the same constant macrocyclic scaffold,following the parallel paradigm to mimic the versatile antibody-like multivalent epitope recognition patterns.We successfully integrated these or-thogonal protecting groups with acylation and made a mock second-generation DNA-encoded display combination.This work illustrates a strategy to produce larger encoded multiple display on a constant macrocyclic scaffold,which could facilitate potential binder discovery with enhanced affinity to clinically significant PPI targets.

Adipose-derived stem cells and obesity: The spear and shield relationship

With the transformation of modern lifestyles and population ageing,obesity has become a global epidemic,as one of the important threat to human health of chronic noncommunicable diseases(NCD).Stem cell therapy seems promising as an alternative strategy for managing obesity and related metabolic problems.Adipose tissue-derived stem cells(ADSCs)have received widespread attention,which provides new ideas for the treatment of obesity and various metabolic-related diseases,due to their abundant reserves,easy acquisition,rapid expansion,and multi-directional differentiation potential,low immunogenicity and many other advantages.Accordingly,there seems to be a"shield and spear paradox"in the relationship between ADsCs and obesity.In this review,we emphatically summarized the role of ADsCs in the occurrence and development of obesity and related metabolic disease processes,in order to pave the way for clinical practice.