Article
Chemistry, Multidisciplinary
Hendrik Hessefort, Angelina Gross, Simone Seeleithner, Markus Hessefort, Tanja Kirsch, Lukas Perkams, Klaus Ole Bundgaard, Karen Gottwald, David Rau, Christopher Guenther Franz Graf, Elisabeth Rozanski, Sascha Weidler, Carlo Unverzagt
Summary: The in-vivo activity of EPO is carbohydrate-dependent, with the number of sialic acid residues regulating its circulatory half-life. A chemoenzymatic approach was developed for obtaining glycoforms of EPO with and without sialic acids. Synthetic EPOs showed biological recognition by forming 1:1 complexes with recombinant EPO receptor.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Applied
Senka Djakovic, Ljubica Glavas-Obrovac, Jasmina Lapic, Silvija Maracic, Juraj Kirchofer, Marija Knezevic, Marijana Jukic, Silvana Raic-Malic
Summary: Conjugated uracil derivatives bridged by 1,2,3-triazole and containing mono-ferrocene or bis-ferrocene units were synthesized. The bis-ferrocenyl uracil derivatives showed better antiproliferative activities, especially on colon adenocarcinoma and Burkitt lymphoma cells, with potential targeting cancer cell mitochondria. This selective cytostatic effect may be attributed to mitochondrial membrane potential disruption and apoptosis induction.
APPLIED ORGANOMETALLIC CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Jun Zhang, Xuefeng Wang, Qi Chen, Jianhe Liu, Wei Zhou, Jie Wu
Summary: A three-component reaction was developed to synthesize various trifluoromethyl-substituted vinyl sulfones with excellent stereoselectivity. Palladium-catalyzed amination was utilized for further modification of these compounds. The antitumor mechanism of these trifluoromethyl-substituted vinyl sulfones in cytotoxic autophagy induced by PI3K/Akt/mTOR signal was investigated.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Yu-Pu Juang, Yu-Ting Chou, Ru-Xian Lin, Hsiu-Hua Ma, Tai-Ling Chao, Jia-Tsrong Jan, Sui-Yuan Chang, Pi-Hui Liang
Summary: 22 niclosamide analogues were synthesized and compound 5 exhibited the best anti-SARS-CoV-2 efficacy. Compounds 5, 6, and 11 showed higher stability and improved oral bioavailability compared to niclosamide.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Zuo-Peng Zhang, Ye Zhong, Zhen-Bin Han, Lin Zhou, Hua-Sheng Su, Jian Wang, Yang Liu, Mao-Sheng Cheng
Summary: A series of saccharide-modified thiadiazole sulfonamide derivatives were designed and synthesized via the tail approach, showing high TPSA values and excellent enzyme inhibitory activity. They exhibited inhibitory effects on various human cancer cell lines and the ability to modulate the pH of the tumor cell microenvironment. These results indicate promising research prospects for the development of CA IX inhibitors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Mpelegeng Victoria Bvumbi, Chris van der Westhuyzen, Edwin M. Mmutlane, Andile Ngwane
Summary: A series of novel riminophenazine derivatives with ionizable alkyl substituents at N-5 and various substituents at C-3, C-8, and on the pendant aryl group were synthesized and investigated for their relationship between lipophilicity, redox potential, and antimycobacterial activity. Results showed a significant activity cliff associated with C-8 substitution, pointing to a potential new class of riminophenazines with reasonable anti-tuberculosis activity.
Article
Chemistry, Medicinal
Joshua Weinmann, Lukas Kirchner, Markus Engstler, Lorenz Meinel, Ulrike Holzgrabe
Summary: Human African trypanosomiasis is a devastating parasitic infection caused by Trypanosoma brucei and transmitted by tsetse flies. Limited treatment options are available, and the quinolone amide MB007 has been identified as a potential lead compound. This study synthesized new quinolone amides to study the structure-activity relationship and improve solubility. The evaluation identified lead structure 9f with promising in vitro activity against T. b. brucei and no cytotoxicity. Compounds 10b and 10c were also discovered, showing improved solubility and selectivity.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Xiang Huan, Yanhui Wang, Xiaofeng Peng, Shanshan Xie, Qian He, Xiaofei Zhang, Lefu Lan, Chunhao Yang
Summary: This study designed and synthesized pyrazole compounds as analogues of pyrrolomycins, and tested their inhibition of Staphylococcus aureus biofilms and antibacterial activity. The results showed that compounds 17a, 17d, and 17h exhibited strong activity against resistant bacteria, and compound 17h significantly reduced the biofilm formation of MRSA with promising selectivity.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Xiao Li, Lun Zhang, Jing Xu, Chenyu Liu, Xiaojian Zhang, Amr Abbas Abdelmoneim, Qian Zhang, Jiaqi Ke, Yingnan Zhang, Lei Wang, Fan Yang, Cheng Luo, Jia Jin, Fei Ye
Summary: This study identified six compounds with significantly improved activities targeting CARM1 through structure-based virtual screening and chemical structural optimizations, with the most potent inhibitor ZL-28-6 exhibiting strong inhibition against other type I PRMTs as well. ZL-28-6 showed increased potency against CARM1 compared to a previous inhibitor, decreased activity against other PRMTs, and better antiproliferation activities in solid tumor cells.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Review
Biochemistry & Molecular Biology
Oluwakemi Ebenezer, Michael Shapi, Jack A. Tuszynski
Summary: Pyrazoles are nitrogen-containing five-membered heterocyclic compounds that are important for drug development and exhibit diverse biological activities. This review summarizes published research on the synthesis and biological activities of pyrazole derivatives.
Article
Chemistry, Medicinal
Yuanju Zhu, Jay Zhang, Feng Min, Xinying Yang, Li Li, Yan Zhang, Xuben Hou, Hao Fang
Summary: The farnesoid X receptor (FXR) is a bile acid activated transcription factor and is involved in important metabolic processes. It is considered a promising therapeutic target for nonalcoholic steatohepatitis (NASH). A series of new FXR agonists were designed in this study, with five compounds showing better activity than the widely used GW4064. The most potent compound S5 also had superior pharmacokinetic profile and in vivo potency compared to the lead compound.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Multidisciplinary
Amalie F. Reinertsen, Karoline G. Primdahl, Roberta De Matteis, Jesmond Dalli, Trond V. Hansen
Summary: The study presented the first total synthesis of RvD2(n-3 DPA), a biologically formed mediator derived from omega-3 fatty acid n-3 docosapentaenoic acid. The synthetic lipid mediator exhibited matching physical properties and biological activities with those of naturally produced material, including enhancing macrophage uptake of bacteria and bioparticles.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Abdelwahed R. Sayed, Hany Elsawy, Saad Shaaban, Sobhi M. Gomha, Yasair S. Al-Faiyz
Summary: In this study, different thiazoles were prepared via a reaction between 2-(3,4-dimethoxybenzylidene)hydrazine-1-carbothioamide (1) and hydrazonoyl halides under base-catalyzed conditions. The structures of the synthesized azo compounds were confirmed, and their potential anticancer activities and ability to promote apoptosis were evaluated. This research provides valuable insights for the development of novel anticancer drugs.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Can Ergun, Mahmut Parmaksiz, Murat Taner Vurat, Ayse Eser Elcin, Yasar Murat Elcin
Summary: A macroporous 3D scaffold derived from decellularized bovine liver ECM was developed with defined biological, physical, and mechanical properties. The scaffold showed stable mechanical performance and high hemocompatibility in vitro. Furthermore, it was demonstrated that the scaffold is suitable for use as a cell substrate.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Chemistry, Multidisciplinary
Koushikul Islam, Marcus Carlsson, Per-Anders Enquist, Weixing Qian, Marko Marttila, Marten Strand, Clas Ahlm, Magnus Evander
Summary: RVFV is an emerging pathogen in Africa with pandemic potential. There is no approved treatment for the virus. Researchers investigated structural modifications of a lead compound and found that the length of the chain was important for maintaining antiviral activity. Changing the position of the linker improved the compound's cytotoxicity profile. The modified compound 13a showed promise as a therapeutic candidate for RVFV infection.
Article
Chemistry, Multidisciplinary
Jiamei Liu, Tongyao Wei, Yi Tan, Heng Liu, Xuechen Li
Summary: This study introduces a new solubilizing tag strategy, utilizing reducible solubilizing tags (RSTs) introduced on the peptide chain for purifying and ligating peptides with poor solubility, featuring operational simplicity and readily accessible materials.
Article
Biochemistry & Molecular Biology
Carina Hey Pui Cheung, Hoi Yee Chow, Can Li, Pilar Blasco, Kaichao Chen, Sheng Chen, Xuechen Li
Summary: In this study, we report a method for the synthesis of a thiolactone analogue and investigate the reaction conditions for optimal results. The developed protocol can be used for the synthesis of other challenging thiolactone peptides.
Article
Biochemistry & Molecular Biology
Hoi Yee Chow, Kathy Hiu Laam Po, Sheng Chen, Xuechen Li
Summary: This study reports the synthesis and antibacterial evaluation of a series of daptomycin lactam-based analogues. The results show that a daptomycin analogue with singly modified lactam has a significantly higher minimum inhibitory concentration against methicillin-resistant Staphylococcus aureus compared to daptomycin. However, incorporating multiple modifications based on previous studies did not improve the antibacterial activity. Instead, replacing the flexible n-decanoyl group with a rigid 4-(phenylethynyl)benzoyl group greatly reduced the antibacterial activity. The inactivity of the lactam analogue with the 4-(phenylethynyl)benzoyl group suggests a deviation from the active conformation. This series of lactam analogues provides insights into the importance of studying the active conformation of daptomycin and the impact of structural modifications on the active conformation.
JOURNAL OF PEPTIDE SCIENCE
(2022)
Article
Chemistry, Multidisciplinary
Hongxiang Wu, Tongyao Wei, Wai Lok Ngai, Haiyan Zhou, Xuechen Li
Summary: This study developed a new synthesis strategy called LEAD for the synthesis of difficult-to-obtain proteins. The strategy effectively disrupts peptide aggregation by generating specific aldehyde compounds, addressing the challenges of aggregable or colloidal peptide segments in solid-phase peptide synthesis and peptide ligation. The effectiveness of this strategy has been demonstrated through the total syntheses of two proteins.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Physical
Tongyao Wei, Dongfang Li, Yue Zhang, Yubo Tang, Haiyan Zhou, Han Liu, Xuechen Li
Summary: Ortho-phthalaldehyde has been found to have wide potentials for protein bioconjugation and peptide cyclization. This study reports a second-generation dialdehyde-based peptide cyclization method using thiophene-2,3-dialdehyde (TDA) that reacts specifically with primary amine and thiol within unprotected peptides, generating a highly stable cyclic structure.
Article
Chemistry, Multidisciplinary
Carina Hey Pui Cheung, Tin Hang Chong, Tongyao Wei, Han Liu, Xuechen Li
Summary: Recently, ortho-phthalaldehyde (OPA) has been used for the modification of proteins and peptides through OPA-amine two-component reactions and intramolecular OPA-amine-thiol three-component reactions. Guanidine has been discovered to be an effective additive in switching the intermolecular OPA-amine-thiol three-component reaction to a stoichiometric process, enabling the construction of peptide-peptide and peptide-drug conjugate structures. This reaction shows great versatility and flexibility, as demonstrated by the successful synthesis of model peptide-peptide and peptide-drug conjugates using unprotected peptides.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Wenjie Ma, Hongxiang Wu, Sha Liu, Tongyao Wei, Xiang David Li, Han Liu, Xuechen Li
Summary: This study developed a new strategy for the synthesis of peptide C-terminal salicylaldehyde esters using Boc-SPPS. The strategy utilized semicarbazone-modified aminomethyl resin and was compatible with all canonical amino acids.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Hongxiang Wu, Yi Tan, Wai Lok Ngai, Xuechen Li
Summary: Chemical synthesis of hydrophobic proteins is challenging, but can be achieved by integrating peptide solubilizing strategies with peptide ligation. This study presents a tunable backbone modification strategy that allows for the introduction of a solubilizing tag for peptide purification and ligation processes. The effectiveness of this strategy was demonstrated by the chemical synthesis of interleukin-2.
Article
Chemistry, Medicinal
Hua-Rui Gong, Ye-fan Hu, Xuechen Li, Thomas Yau, Bao-Zhong Zhang, Jian-Dong Huang
Summary: This study investigates the infection enhancement effect of a multiple epitope-based vaccine on the Omicron strain of SARS-CoV-2. The results show that while the vaccine enhances infection for Omicron, it does not have the same effect on the ancestral SARS-CoV-2 or Delta strains. Furthermore, the study identifies a conserved epitope that has neutralizing activity against the three strains. This research provides up-to-date epitope information for guiding the development of better vaccines or antibody-based therapies against future variants.
ACS INFECTIOUS DISEASES
(2022)
Article
Chemistry, Organic
Xing Guo, Boming Shen, Chang Liu, Hongyue Zhao, Xuechen Li, Peiyuan Yu, Pengfei Li
Summary: Based on the frontier molecular orbital theory, two types of modified enones have been designed and successfully applied in the chiral phosphine-catalyzed stereoselective [1 + 4]-annulation of MBH carbonates. The reaction proceeds smoothly under mild conditions, exhibiting excellent functional group tolerance and providing a broad scope of enantioenriched 2,3-dihydrofurans with high efficiency. DFT calculations have been used to guide the design of additional enones and understand the origin of stereoselectivity. Furthermore, this method explores the application scope of enones and enriches the chemistry of [1 + 4]-annulations of MBH carbonates for the preparation of optically active multifunctional 2,3-dihydrofurans.
ORGANIC CHEMISTRY FRONTIERS
(2022)
Article
Chemistry, Organic
Yue Zhang, Ruijuan Yin, Hao Jiang, Chaoming Wang, Xiao Wang, Dongping Wang, Kai Zhang, Rilei Yu, Xuechen Li, Tao Jiang
Summary: In this study, a new method for peptide stapling using bifunctional triazine moieties was developed. This method efficiently stabilizes unprotected peptides by conjugating to the phenolic hydroxyl groups of tyrosine. The application of this method to the RGD peptide, which targets integrins, showed significantly improved plasma stability and integrin-targeting ability.
Article
Biochemical Research Methods
Zhenquan Sun, Tongyao Wei, Yihui Cao, Xuechen Li
Summary: In this paper, a rapid protein desulfurization protocol in combination with native chemical ligation is presented for the facile synthesis of proteins with site-specific modifications. The authors demonstrate the use of sodium tetraethylborate (NaBEt4) for this desulfurization, which can be carried out under ambient conditions without the need for inert atmosphere protection, UV irradiation, heating, or exogenous thiol additives. Specifically, the semisynthesis of serotonylated histone H3 (H3Q5ser) via one-pot ligation desulfurization is detailed. This protocol can be used to synthesize proteins of interest with homogeneous post-translational modifications.
Article
Chemistry, Multidisciplinary
Hongxiang Wu, Zhenquan Sun, Xuechen Li
Summary: In this study, we introduced N,O-benzylidene acetal dipeptides (NBDs) as robust and effective building blocks for the direct synthesis of difficult peptides and proteins. The versatility of NBDs was demonstrated in the successful synthesis of various challenging peptides and proteins, including chemokine, therapeutic hormones, histone, and glycosylated erythropoietin.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Review
Biochemistry & Molecular Biology
Wenjie Ma, Han Liu, Xuechen Li
Summary: S-palmitoylation and O-acetylation are two base-labile post-translational modifications (PTMs) in cells. The lability of these PTMs makes their synthesis challenging. This review summarizes the efforts towards the preparation of S-palmitoyl and O-acetyl modified peptides/proteins in the past 40 years, focusing on the evolution of synthetic methods.
Review
Chemistry, Organic
Xing Guo, Pengfei Li, Han Liu, Xuechen Li
Summary: Bacteria resistant to antibiotics pose a threat to public health. Non-2-ulosonic acids, including pseudaminic acid, legionaminic acid, acinetaminic acid, fusaminic acid, and their epimers, are found in pathogenic Gram-negative bacteria and are believed to be associated with bacterial infection/pathogenicity and immune escape. Their unique structures and poorly understood biological functions make them attractive targets for synthetic studies and drug discovery. This review summarizes the chemical syntheses of four types of non-2-ulosonic acid structures reported in the past two decades and discusses recent progress in the application of synthetic non-2-ulosonic acid derivatives.
ORGANIC CHEMISTRY FRONTIERS
(2023)
