期刊：
European Journal of Medicinal Chemistry,2024年263:115956 ISSN：0223-5234
通讯作者：
Mi, Pengbing;Yuan, Zhonghua;Zheng, X;Lin, YW
作者机构：
[Tan, Yan; Yuan, Zhonghua; Mi, Pengbing; Jiang, Jinhuan; Chen, Limei; Luo, Jianxiong; Zheng, Xing; Ye, Shiying; Lin, Yuqing; Zheng, X] Univ South China, Dept Pharm, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Lang, Jia-Jia; Lin, Ying-Wu] Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Hunan, Peoples R China.;[Lang, Jia-Jia; Lin, Ying-Wu; Mi, Pengbing] Univ South China, Key Lab Prot Struct & Funct Univ Hunan Prov, Hengyang 421001, Hunan, Peoples R China.;[Zheng, Xing] Hunan Vocat Coll Sci & Technol, Dept Pharm, Changsha 410004, Hunan, Peoples R China.;[Lv, You] Shaanxi Univ Sci & Technol, Coll Bioresources Chem & Mat Engn, Xian 710021, Shaanxi, Peoples R China.
通讯机构：
[Yuan, ZH; Mi, PB; Lin, YW ; Zheng, X ] U;Univ South China, Dept Pharm, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Hunan, Peoples R China.
关键词：
Human monoamine oxidase B inhibitor;Thiochromone;Thiochromone S,S-dioxide
摘要：
Developing new scaffolds for highly potent and selective inhibitors of human Monoamine Oxidase B (hMAO-B) is a crucial objective in enhancing the efficacy and safety in the clinical treatment of neurodegenerative diseases. In this study, we have identified a series of C-3 isoxazole-substituted thiochromone S,S-dioxide derivatives that exhibit strong inhibitory activity against hMAO-B. The strategy of oxidizing thiochromone to thiochromone S,S-dioxide solves the key defect of extreme insolubility observed for thiochromone analogues. In addition, the sulfone group contributes extra hydrogen(H)-bonding interactions with Tyr435, which significantly increases the activity of thiochromone S,S-dioxide derivatives against hMAO-B. Furthermore, the presence of isoxazole group provides potential H-bonding interaction and electrostatic interaction with the residue of Tyr326, while the rigid aryl ring introduces a potential steric conflict with Phe208 of hMAO-A to improve both potency and selectivity. In our investigations, several compounds (9c, 10c, 10e, 10g, 10l and 10m) demonstrate remarkable single-digit nanomolar potency. These compounds exhibit favorable cytotoxicity profiles in both differentiated SH-SY5Y and HVSMC cells, without apparent cardiotoxic effects. Moreover, compounds 10e and 10h do not lead to an increase in ROS levels in differentiated SH-SY5Y cells, further demonstrating their potential as safe and effective hMAO-B inhibitors. These findings indicate that the C-3 isoxazole substituted thiochromone S,S-dioxide analogues are potential leading compounds for the development of selective inhibitors with high potency.
摘要：
The development of highly selective Janus Kinase 1 (JAK1) inhibitors is crucial for improving efficacy and minimizing adverse effects in the clinical treatment of autoimmune diseases. In a prior study, we designed a series of C-5 4-pyrazol substituted pyrrolopyridine derivatives that demonstrated significant potency against JAK1, with a 10∼20-fold selectivity over Janus Kinase 2 (JAK2). Building on this foundation, we adopted orthogonal strategy by modifying the C-5 position with 3-pyrazol/4-pyrazol/3-pyrrol groups and tail with substituted benzyl groups on the pyrrolopyridine head to enhance both potency and selectivity. In this endeavor, we have identified several compounds that exhibit excellent potency and selectivity for JAK1. Notably, compounds 12b and 12e, which combined 4-pyrazol group at C-5 site and meta-substituted benzyl tails, displayed IC(50) value with 2.4/2.2nM and high 352-/253-fold selectivity for JAK1 over JAK2 in enzyme assays. Additionally, both compounds showed good JAK1-selective in Ba/F3-TEL-JAK1/2 cell-based assays. These findings mark a substantial improvement, as these compounds are 10-fold more potent and over 10-fold more selective than the best compound identified in our previous study. The noteworthy potency and selectivity properties of compounds 12b and 12e suggest their potential utility in furthering the development of drugs for autoimmune diseases.
期刊：
PHYSICAL CHEMISTRY CHEMICAL PHYSICS,2024年26(2):1077-1085 ISSN：1463-9076
通讯作者：
Chuan-Wan Wei<&wdkj&>Ying-Wu Lin
作者机构：
[Gao, Shu-Qin] Key Lab of Protein Structure and Function of Universities in Hunan Province, University of South China, Hengyang 421001, China;[Wang, Xiao-Juan; Long, Yan; Wei, Chuan-Wan] School of Chemistry and Chemical Engineering, University of South China, Hengyang 421001, China;[Lin, Ying-Wu] School of Chemistry and Chemical Engineering, University of South China, Hengyang 421001, China<&wdkj&>Key Lab of Protein Structure and Function of Universities in Hunan Province, University of South China, Hengyang 421001, China
通讯机构：
[Chuan-Wan Wei; Ying-Wu Lin] S;School of Chemistry and Chemical Engineering, University of South China, Hengyang 421001, China<&wdkj&>Key Lab of Protein Structure and Function of Universities in Hunan Province, University of South China, Hengyang 421001, China<&wdkj&>School of Chemistry and Chemical Engineering, University of South China, Hengyang 421001, China
摘要：
A Cu-Fe bimetallic hydrogel (2-QF-CuFe-G) was constructed through a simple method. The 2-QF-CuFe-G metallohydrogel possesses excellent peroxidase-like activity to catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H(2)O(2). The catalytic mechanism was confirmed by the addition of (•)OH radical scavenger isopropyl alcohol (IPA), tert-butyl alcohol (TBA) and ˙OH trapping agent terephthalic acid (TA). Remarkably, the resultant blue ox-TMB system can be used to selectively and sensitively detect ascorbic acid (AA) with an LOD of 0.93 μM in the range of 4-36 μM through the colorimetric method. Moreover, the assay based on the 2-QF-CuFe-G metallohydrogel can be successfully applied to detect AA in fresh fruits.
作者机构：
[Liu, Xi-Chun; Nie, Lv-Suo; Lin, Ying-Wu] Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Peoples R China.;[Liu, Ao-Kun; Yu, Lu] Chinese Acad Sci, High Magnet Field Lab, Hefei 230031, Anhui, Peoples R China.;[Gao, Shu-Qin; Sun, Li-Juan; Lin, Ying-Wu] Univ South China, Hengyang Med Sch, Hengyang 421001, Peoples R China.
通讯机构：
[Lin, YW ] U;Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Peoples R China.;Univ South China, Hengyang Med Sch, Hengyang 421001, Peoples R China.
摘要：
In this study, we constructed a metal-binding site close to the heme cofactor in myoglobin (Mb) by covalently attaching a nonnative metal-binding ligand of bipyridine to Cys46 through the F46C mutation in the heme distal site. The X-ray structure of the designed enzyme, termed F46C-mBpy Mb, was solved in the Cu(II)-bound form, which revealed the formation of a heterodinuclear center of Cu-His-H(2)O-heme. Cu(II)-F46C-mBpy Mb exhibits not only nitrite reductase reactivity but also cascade reaction activity involving both hydrolysis and oxidation. Furthermore, F46C-mBpy Mb displays Mn-peroxidase activity by the oxidation of Mn(2+) to Mn(3+) using H(2)O(2) as an oxidant. This study shows that the construction of a nonnative metal-binding site close to the heme cofactor is a convenient approach to creating an artificial metalloenzyme with a heterodinuclear center that confers multiple functions.
摘要：
Globins, such as myoglobin (Mb) and neuroglobin (Ngb), are ideal protein scaffolds for the design of functional metalloenzymes. To date, numerous approaches have been developed for enzyme design. This review presents a summary of the progress made in the design of functional metalloenzymes based on Mb and Ngb, with a focus on the exploitation of covalent interactions, including coordination bonds and covalent modifications. These include the construction of a metal-binding site, the incorporation of a non-native metal cofactor, the formation of Cys/Tyr-heme covalent links, and the design of disulfide bonds, as well as other Cys-covalent modifications. As exemplified by recent studies from our group and others, the designed metalloenzymes have potential applications in biocatalysis and bioconversions. Furthermore, we discuss the current trends in the design of functional metalloenzymes and highlight the importance of covalent interactions in the design of functional metalloenzymes.
作者机构：
[Gao, Shu-Qin; Sun, Li-Juan; Lin, Ying-Wu] Univ South China, Hengyang Med Sch, Hengyang 421001, Peoples R China.;[Wang, Huamin; Niu, Wenjing; Lin, Ying-Wu] Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Peoples R China.;[Xu, Jia-Kun] Chinese Acad Fishery Sci, Yellow Sea Fisheries Res Inst, Key Lab Sustainable Dev Polar Fisheries, Qingdao 266071, Peoples R China.
通讯机构：
[Lin, YW ] U;Univ South China, Hengyang Med Sch, Hengyang 421001, Peoples R China.;Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Peoples R China.
摘要：
Organoborons have recently received much attention, while a biocatalytic platform for the synthesis of chiral organoborons is limited only to Rma cytochrome c. In this study, we exploited the other heme protein, neuroglobin (Ngb), and engineered a quadruple mutant, A15C/H64G/V68F/F28M Ngb, by redesigning the heme active site using the structural information on A15C Ngb and molecular docking studies. The enzyme was shown to be efficient in catalyzing carbene transfer B-H insertion reactions between pyridine/quinoline boranes and benzyl 2-diazopropanoates and their derivatives (29 examples). The designed cavity in the heme distal site favors the binding of large volume substrates such as those containing a quinoline, naphthyl, or biphenyl group. As further determined by the X-ray crystallography of 6c, the chiral products are in the R-configuration, with up to 98:2 e.r. Furthermore, both the whole cell and cell lysate containing the enzyme are reactive toward the B-H insertion reactions. This study presents a convenient biocatalytic platform that may be generally applicable for the synthesis of functional chiral organoborons.
期刊：
Chemical Communications,2024年60(54):6961-6964 ISSN：1359-7345
通讯作者：
Wang, Huamin;Lin, YW
作者机构：
[Wang, Huamin; Cheng, Xiufang; He, Yongjun; Wei, Yibo; Lin, Ying-Wu; He, Tian-Juan; Wang, HM] Univ South China, Sch Chem & Chem Engn, Hengyang, Peoples R China.;[Lin, Ying-Wu] Univ South China, Lab Prot Struct & Funct, Med Sch, Hengyang, Peoples R China.
通讯机构：
[Lin, YW ; Wang, HM] U;Univ South China, Sch Chem & Chem Engn, Hengyang, Peoples R China.;Univ South China, Lab Prot Struct & Funct, Med Sch, Hengyang, Peoples R China.
摘要：
An efficient phosphine-catalyzed dearomative [3+2] annulation of 4-nitroisoxazoles with allenoates or Morita–Baylis–Hillman carbonates has been established for the convenient synthesis of bicyclic isoxazoline derivatives. This reaction approach showed a broad substrate scope, high functional group compatibility, and excellent regioselectivity and diastereoselectivity. Furthermore, the success at the gram-scale and synthetic applications of the obtained compound 3a demonstrate the great potential of this methodology for practical applications in organic synthesis.
作者机构：
[Guo, Pengfei; Lin, Ying-Wu; Yu, Qiufan; Liu, Xichun; Liu, XC] Univ South China, Sch Chem & Chem Engn, Hengyang, Peoples R China.;[Gao, Shu-Qin; Lin, Ying-Wu] Univ South China, Hengyang Med Sch, Key Lab Prot Struct & Funct Univ Hunan Prov, Hengyang, Peoples R China.;[Yuan, Hong; Tan, Xiangshi] Fudan Univ, Dept Chem, Shanghai, Peoples R China.;[Yuan, Hong; Tan, Xiangshi] Fudan Univ, Inst Biomed Sci, Shanghai, Peoples R China.
通讯机构：
[Lin, YW ; Liu, XC] U;Univ South China, Sch Chem & Chem Engn, Hengyang, Peoples R China.;Univ South China, Hengyang Med Sch, Key Lab Prot Struct & Funct Univ Hunan Prov, Hengyang, Peoples R China.
摘要：
Allosteric conformational change is an important paradigm in the regulation of protein function, which is typically triggered by the binding of small cofactors, metal ions or protein partners. Here, we found those conformational transitions can be effectively monitored by 19F NMR, facilitated by a site-specific 19F incorporation strategy at the protein C-terminus using asparaginyl endopeptidase (AEP). Three case studies show that C-terminal 19F-nuclei can reveal protein dynamics not only adjacent but also distal to C-terminus, including those occurring in a hemoprotein neuroglobin (Ngb), calmodulin (CaM), and a cobalt metalloregulator (CoaR) responding to both cobalt and tetrapyrrole. In Ngb, the heme orientation disorder is affected by missense mutations that perturb backbone rigidity or surface charges close to the heme axial ligands. In CaM, the C-terminal 19F-nuclei is an ideal probe for detecting the binding states of Ca2+, peptides and inhibitors. Furthermore, multiple 19F-moieties were incorporated into the two domains of CoaR, revealing the intrinsically disordered C-terminal metal binding tail might be an allosteric conformational switch to maintain cobalt homeostasis and balance corrinoid biosynthesis. This study demonstrates that the AEP-based 19F-modification strategy can be applied to various targets to study allosteric regulation, especially for those biological processes modulated by the protein C-terminus. The site-specific 19F labeling at protein C-terminus catalyzed by OaAEP1C247A is an efficient approach to utilize 19F NMR, which is compatible with the genetic code expansion technology. Three cases studies show this approach is suitable for probing allosteric conformational transitions in metalloproteins.
期刊：
Chemical Communications,2024年60(85):12425-12428 ISSN：1359-7345
通讯作者：
Wang, Huamin;Lin, YW
作者机构：
[Wang, Huamin; Meng, Li-Qin; Ou, Yu; Niu, Wenjing; Lin, Ying-Wu; Wang, HM; Yang, Wan-Qi] Univ South China, Sch Chem & Chem Engn, Hengyang, Peoples R China.;[Lin, Ying-Wu] Univ South China, Med Sch, Lab Prot Struct & Funct, Hengyang, Peoples R China.
通讯机构：
[Lin, YW ; Wang, HM] U;Univ South China, Sch Chem & Chem Engn, Hengyang, Peoples R China.;Univ South China, Med Sch, Lab Prot Struct & Funct, Hengyang, Peoples R China.
摘要：
A general and practical K(2)CO(3)-promoted [3+2] annulation between trifluoroacetaldehyde N-triftosylhydrazone (TFHZ-Tfs) and 4-nitroisoxazoles has been developed to access structurally diverse trifluoromethylpyrazolo[3,4-d]isoxazoles. Mechanistically, CF(3)CHN(2) is formed in situ by TFHZ-Tfs decomposition and involves a formal [3+2] dearomative cycloaddition with 4-nitroisoxazoles, followed by aromatization via the elimination of the nitro group. Furthermore, this protocol is metal-free, scalable, mild, and operationally safe, with a broad substrate scope and high functional group compatibility.
摘要：
A Mn-based nanozyme, Mn-uNF/Si, with excellent alkali phosphatase-like activity was designed by in-situ growth of ultrathin Mn-MOF on the surface of silicon spheres, and implemented as an effective solid Lewis-Brønsted acid catalyst for broad-spectrum dephosphorylation. H(2)(18)O-mediated GC-MS studies confirmed the cleavage sites and the involvement of H(2)O in the new bonds. DRIFT NH(3)-IR and in-situ ATR-FTIR confirmed the coexistence of Lewis-Brønsted acid sites and the adjustment of adsorption configurations at the interfacial sites. In addition, a green transformation route of "turning waste into treasure" was proposed for the first time ("OPs→PO(4)(3-)→P food additive") using edible C. reinhardtii as a transfer station. By alkali etching of Mn-uNF/Si, a nanozyme Mn-uNF with laccase-like activity was obtained. Intriguingly, glyphosate exhibits a laccase-like fingerprint-like response (+,-) of Mn-uNF, and a non-enzyme amplified sensor was thus designed, which shows a good linear relationship with Glyp in a wide range of 0.49-750μM, with a low LOD of 0.61μM, as well as high selectivity and anti-interference ability under the co-application of phosphate fertilizers and multiple pesticides. This work provides a controllable methodology for the design of bifunctional nanozymes, which sheds light on the highly efficient green transformation of OPs, and paves the way for the selective recognition and quantification of glyphosate. Mechanistically, we also provided deeper insights into the structure-activity relationship at the atomic scale.
摘要：
Inspired by the hydrolysis behaviors of skin cells, we exquisitely designed and synthesized a class of hydrolase mimics to develop an analytical method that can both identify and quantity antioxidant components in skin-whitening cosmetics, including ascorbic acid (AA) and its glycoside and phosphate derivatives. A series of ultra-thin Cu1-xMnxO2 or Fe1-yMnyO2 with rich acid-base pairs were prepared via chemical deposition and in-situ Cu-I/Fe-II self-assembly. (H2O)-O-18 and (D2O)-O-16 isotopic labeling studies and density function theory (DFT) calculations were adopted to analyze the cleaving sites of ascorbyl phosphate (AAL)/ascorbyl glucoside (AAP) and confirm that H2O was involved in the new bonds. In -situ DRIFT NH3-IR and -TPD further confirmed that the Fe- or Cu-substitution could increase the quantity and strength of Bronsted and Lewis acid sites. A cascade catalytic fluorescence sensor was designed for selective recognition or quantification of AA and its derivatives, which presents ultra-high-precision (<= 2.5 %), stability, and selectivity in testing the target ingredients of five cosmetics from the market. Our nanozymes exhibit higher catalytic efficiency of 17.1 s(-1) for AA, 8.42 s(-1) for AAL, and 3.32 s(-1) for AAP, which are 5.6 similar to 32.8 -fold higher than those of their mimic proteases. This work provides a controllable methodology to design hydrolytic nanozymes, which sheds light on biomimetic engineering and paves the way for breakthroughs in cosmetics industrial applications in the future.
期刊：
JOURNAL OF ORGANIC CHEMISTRY,2024年89(14):10093-10098 ISSN：0022-3263
通讯作者：
Wang, Huamin;Lin, YW
作者机构：
[Wang, Huamin; Wei, Yibo; He, Yongjun; Lin, Ying-Wu; He, Tian-Juan; Wang, HM] Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Peoples R China.;[Lin, Ying-Wu] Univ South China, Hengyang Med Coll, Hengyang 421001, Peoples R China.;[Lin, Ying-Wu] Univ South China, Med Sch, Lab Prot Struct & Funct, Hengyang 421001, Peoples R China.
通讯机构：
[Lin, YW ; Wang, HM] U;Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Peoples R China.;Univ South China, Hengyang Med Coll, Hengyang 421001, Peoples R China.;Univ South China, Med Sch, Lab Prot Struct & Funct, Hengyang 421001, Peoples R China.
摘要：
A series of amides, including α-bromo hydroxamates, N-alkoxyamides, and N-aryloxyamides, were subjected to phosphine-catalyzed ring-opening O-selective addition with cyclopropenones, producing various special α,β-unsaturated esters containing oxime ether motif, in moderate to excellent yields, with high regioselectivity, and exclusive O-selectivity. The methodology is highly atom-economical, with simple operation procedures, and compatible with a wide substrate scope (more than 44 examples).
期刊：
Journal of Inorganic Biochemistry,2024年262:112733 ISSN：0162-0134
通讯作者：
Meng, Xiangmin;Lin, Ying-Wu;Xu, Jiakun
作者机构：
[Yang, Yadan; Zhang, Weikang; Wang, Fang] State Key Laboratory of Mariculture Biobreeding and Sustainable Goods, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China;[Yang, Yadan; Zhang, Weikang] College of Marine Science and Biological Engineering, Qingdao University of Science and Technology, Qingdao 266042, China;[Meng, Xiangmin] College of Marine Science and Biological Engineering, Qingdao University of Science and Technology, Qingdao 266042, China. Electronic address: mengxiangmin@qust.edu.cn;[Lin, Ying-Wu] School of Chemistry and Chemical Engineering, University of South China, Hengyang 421001, China. Electronic address: ywlin@usc.edu.cn;[Xu, Jiakun] State Key Laboratory of Mariculture Biobreeding and Sustainable Goods, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China. Electronic address: xujk@ysfri.ac.cn
通讯机构：
[Meng, Xiangmin] C;[Lin, Ying-Wu; Xu, Jiakun] S;College of Marine Science and Biological Engineering, Qingdao University of Science and Technology, Qingdao 266042, China. Electronic address:;School of Chemistry and Chemical Engineering, University of South China, Hengyang 421001, China. Electronic address:;State Key Laboratory of Mariculture Biobreeding and Sustainable Goods, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China. Electronic address:
摘要：
A novel artificial peroxidase has been developed for the efficient degradation of the non-steroidal anti-inflammatory drug meloxicam by combining computer simulation and genetic engineering techniques. The results showed that the artificial peroxidase was able to completely degrade meloxicam within 90s, with a degradation rate of 100%, which was much higher than that of natural lacquer (46%). The reaction time of the artificial enzyme was significantly shorter than that of natural peroxidase (10min) and laccase (48h). Further studies showed that the amino acid arrangement of the active site of the protein plays an important role in the catalytic performance. The degradation pathway of meloxicam was revealed using UPLC-MS analysis. In vitro toxicity assay showed complete disappearance of toxicity after meloxicam degradation. Therefore, the biocatalytic system proved to be an effective route for the green degradation of meloxicam with important application potential.
作者机构：
[Wang, Huamin; Lin, Ying-Wu; Chen, Ze-Yuan] Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Peoples R China.;[Yuan, Hong; Tan, Xiangshi] Fudan Univ, Dept Chem, Shanghai 200433, Peoples R China.;[Yuan, Hong; Tan, Xiangshi] Fudan Univ, Inst Biomed Sci, Shanghai 200433, Peoples R China.;[Gao, Shu-Qin; Sun, Li-Juan; Lin, Ying-Wu] Univ South China, Hengyang Med Sch, Hengyang 421001, Peoples R China.;[Yu, Lu] Chinese Acad Sci, High Magnet Field Lab, Hefei 230031, Anhui, Peoples R China.
通讯机构：
[Lin, YW ] U;Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Peoples R China.;Univ South China, Hengyang Med Sch, Hengyang 421001, Peoples R China.
关键词：
heme active site;heme proteins;protein engineering;covalent modification;X-ray structure
摘要：
Covalent modification: A facial approach was developed to regulate the heme active site of heme protein by cavity generation, followed by covalent modifications, as shown by the two case studies using myoglobin as a model protein. Abstract Using myoglobin (Mb) as a model protein, we herein developed a facial approach to modifying the heme active site. A cavity was first generated in the heme distal site by F46 C mutation, and the thiol group of Cys46 was then used for covalently linked to exogenous ligands, 1H‐1,2,4‐triazole‐3‐thiol and 1‐(4‐hydroxyphenyl)‐1H‐pyrrole‐2,5‐dione. The engineered proteins, termed F46C‐triazole Mb and F46C‐phenol Mb, respectively, were characterized by X‐ray crystallography, spectroscopic and stopped‐flow kinetic studies. The results showed that both the heme coordination state and the protein function such as H2O2 activation and peroxidase activity could be efficiently regulated, which suggests that this approach might be generally applied to the design of functional heme proteins.
摘要：
Heme proteins play various important roles in a variety of physiological and pathological processes. Sur-factant assemblies have drawn great attention in fabricating fluorescent sensors to detect and identify proteins. In this study, an acetylpyrene fluorophore containing imidazole HP-1 was synthesized, and it could be well modulated by an anionic surfactant sodium dodecyl sulfate (SDS). The selected ensemble based on HP-1/SDS assemblies exhibited selective fluorescence sensing performance towards the heme proteins, including neuroglobin (Ngb), myoglobin (Mb) and cytochrome c (Cyt c ). Besides, phospholipid DMPC vesicles as membrane models were particularly explored the association process between the heme protein Mb and membrane. The present work showed that Mb induced the lysis of DMPC lipo-somes visualized by transmission electron microscopy and optical microscope.(c) 2023 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.
摘要：
Natural and artificial nucleases have extensive applications in biotechnology and biomedicine. The exploration of protein with potential DNA cleavage activity also inspires the design of artificial nuclease and helps to understand the physiological process of DNA damage. In this study, we engineered four human cytochrome c (Cyt c) mutants (N52S, N52A, I81N, and I81D Cyt c), which showed enhanced DNA cleavage activity and degradation in comparison with WT Cyt c, especially under acidic conditions. The mechanism assays revealed that the superoxide (O2 & BULL; ) plays an important role in the nuclease reaction. The kinetic assays showed that the peroxidase activity of the I81D Cyt c mutant enhanced up to 9-fold at pH 5. This study suggests that the mutations of Ile81 and Asn52 in & omega;-loop C/D are critical for the nuclease activity of Cyt c, which may have physiological significance in DNA damage and potential applications in biomedicine.
作者机构：
[Liu, Jing-Jing; Baek, Kitae; Abeysinghe, Shakya; Kim, Hye-Bin; Kim, Jong-Gook] Jeonbuk Natl Univ, Dept Environm & Energy, 567 Baekje Daero, Jeonju Si, Jeollabukdo, South Korea.;[Liu, Jing-Jing; Baek, Kitae; Abeysinghe, Shakya; Kim, Hye-Bin; Kim, Jong-Gook] Jeonbuk Natl Univ, Soil Environm Res Ctr, 567 Baekje Daero, Jeonju Si, Jeollabukdo, South Korea.;[Liu, Jing-Jing; Lin, Ying-Wu] Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Peoples R China.
通讯机构：
[Kitae Baek] D;Department of Environment & Energy and Soil Environment Research Center, Jeonbuk National University, 567 Baekje-daero, Deokjin-gu, Jeonju-si, Jeollabukdo, Republic of Korea
关键词：
Adsorption;Enzyme;Horseradish peroxidase;Hydrogen peroxide;Oxidation;Supporting material
