个人简介
EDUCATION
2005 B.S., Peking University, Beijing, China
2010 Ph.D. University of Maryland, College Park, Maryland, USA Advisor: Prof. Steven E. Rokita Thesis Title: Reversible DNA Alkylation of Quinone Methides
POSITIONS SINCE FINAL DEGREE
2010-2014 Postdoctoral Fellow, University of Illinois at Urbana-Champaign Advisor: Prof. Wilfred van der Donk Project: Biosynthesis of peptide natural products
2014-2015 Associate Professor Department of Chemistry and Chemical Engineering Nanjing University
2015-present Professor Department of Chemistry and Chemical Engineering Nanjing University
研究领域
We are a Chemical Biology group that aims to address problems at the interface of chemistry and biochemistry, including the chemical synthesis and biosynthesis of bioactive peptides, protein functionalization and biological function of non-coding RNA in bacteria.
Macrocycles Are Great Cycles!
Biologically active macrocycles represent a remarkably diverse group of molecules and are emerging as an exciting area of medicinal chemistry. Macrocycles in drug discovery are defined as molecules containing at least one large ring composed of 12 or more atoms. Many natural products have a macrocyclic core, suggesting that an evolutionary advantage may be associated with the production of secondary metabolites based upon these scaffolds. Our group is particularly interested in macrocyclic peptides from both natural and synthetic sources. We are engaged in elucidating Nature’s strategy to utilize various enzymes to produce cyclic peptide natural products. The chemistry evolved by Nature further guides us to develop synthetic methods for peptide macrocyclization and diversification, which would lead to library of peptide/peptidomimetics for screening bioactive compounds.
Chemical Mutagenesis of Proteins
The structural diversity of proteins is directly related to their biological functions. In nature, post-translational modification (PTM) is the key means by which non-proteinogenic amino acids are incorporated. Chemical modification of proteins has the potential to expand their function by mimicking PTMs. Methods for site-specific modification of proteins are invaluable in generating biological therapeutic agents, such as antibody-drug conjugates (ADCs) and PEGylated biologics. We are aimed to develop new chemistry and bioconjugation reagents for the efficient and selective modification of proteins.
Biological Functions of Noncoding RNA
The central dogma of molecular biology summarizes the flow of genetic information within a biological system as “DNA makes RNA, which encodes protein.” However, numerous DNA segments in the genome produce RNA transcripts that do not encode proteins, therefore named noncoding RNAs (ncRNAs). ncRNAs participate in the post-transcriptional regulation and are essential for biological systems to function correctly. MicroRNAs are a class of small ncRNAs that exert their regulatory functions through RNA interference by guiding Argonaute ribonucleases to specific complementary targets. We are particularly interested in the role of miRNAs in cross-kingdom regulation between eukaryotic and prokaryotic species.
近期论文
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Jingxia Lu, Yuan Wu, Yuqing Li and Huan Wang* Utilization of Lanthipeptide Synthetases is a General Strategy for the Biosynthesis of 2-Aminovinyl-Cysteine Motifs in Thioamitides, Angew. Chem. Int. Ed. 2021, 60, 1951-1958.
Jingxia Lu,† Yuqing Li†,Zengbing Bai, Hongmei Lv and Huan Wang* Enzymatic macrocyclization of ribosomally synthesized and posttranslational modified peptides via C–S and C–C bond formation, Nat. Prod. Rep., 2021, 38, 981.（†Equal contribution)
Shu Liu, Chuangxu Cai, Zengbing Bai, Wangjian Sheng, Jiantao Tan* and Huan Wang* Late-stage Macrocyclization of Bioactive Peptides with Internal Oxazole Motifs via Palladium Catalyzed C-H Olefination, Org. Lett. 2021,23, 2933–2937.
Tengfang Long,† Lei Liu,† Youqi Tao, Wanli Zhang, Jiale Quan, Jie Zheng, Julian D. Hegemann, Motonari Uesugi, Wenbing Yao, Hong Tian* and Huan Wang* Light-controlled Tyrosine Nitration of Proteins, Angew. Chem. Int. Ed. 2021, 60, 2-11. （†Equal contribution)
Wangjian Sheng, Bing Xu, Shaoming Chen, Yuqing Li, Bin Liu and Huan Wang*，Substrate tolerance of the biosynthetic enzymes of glycosylated lanthipeptide NAI-112, Org. Biomol. Chem.2020,18, 6095
Zengbing Bai and Huan Wang*, Backbone-Enabled Peptide Macrocyclization through Late-Stage Palladium-Catalyzed C–H Activation, Synlett. 2020, 31, 199-204. DOI: 10.1055/s-0039-1691495
Zengbing Bai, Chuangxu Cai, Wangjian Sheng, Yuxiang Ren and Huan Wang*, Late-Stage Peptide Macrocyclization via Palladium-Catalyzed Site-selective C-H Olefination of Tryptophan, Angew. Chem. Int. Ed. 2020,59, 14686-14692.
Jingxia Lu,# Jiao Li,# Yuan Wu, Xianyang Fang, Jiapeng Zhu* and Huan Wang*, Characterization of the FMN-Dependent Cysteine Decarboxylase from Thioviridamide Biosynthesis, Org. Lett. 2019, 21, 4674-4679. （# Both authors contribute equally.）
Jiantao Tan, Jie Wu, Shu Liu, Hequan Yao and Huan Wang*, Macrocyclization of Peptidoarylacetamides with Self-assembly Properties through Late-stage Palladium-catalyzed C(sp2)-H Olefination, Sci. Adv. 2019, 5, eaaw0323.
Shaoming Chen, Bing Xu, Erquan Chen, Jiaqi Wang, Jingxia Lu, Huiming Ge and Huan Wang*, Zn-dependent Bifunctional Proteases are Responsible for Leader Peptide Processing of Class III Lanthipeptides, PNAS, 2019, 116, 2533-2538.
Qunfeng Luo, Youqi Tao, Wangjian Sheng, Jingxia Lu and Huan Wang*, Dinitroimidazoles as Bifunctional Bioconjugation Reagents for Protein Functionalization and Peptide Macrocyclization, Nat. Commun. 2019, 10, 142.
Jian Tang, Hongfei Chen, Yadong He, Wangjian Sheng, Qingqing Bai and Huan Wang*, Peptide-guided functionalization and macrocyclization of bioactive peptidosulfonamides by Pd(II)-catalyzed late-stage C–H activation, Nat. Comm. 2018, 9, 3383.
Zengbing Bai, Chuangxu Cai, Zonglun Yu and Huan Wang*, Backbone-Enabled Directional Peptide Macrocyclization through Late-Stage Palladium-Catalyzed δ-C(sp2)-H Olefination, Angew. Chem. Int. Ed.2018, 57, 13912-13916.
Jian Tang, Jingxia Lu, Qunfeng Luo and Huan Wang*, Discovery and biosynthesis of thioviridamide-like compounds, Chinese Chem. Lett.2018, 29, 1022-1028.
Jie Wu, Jian Tang, Hongfei Chen, Yadong He, Hequan Yao* and Huan Wang*,Recent developments in peptide macrocyclization, Tetrahrdron Lett., 2018, 59, 325-333.
Erquan Chen, Qi Chen, Shaoming Chen, Bing Xu, Jianhua Ju and Huan Wang*, Mathermycin, a Lantibiotic from the Marine Actinomycete Marinactinospora thermotolerans SCSIO 00652, Appl. Environ. Microbio. 2017, 83, e00926-17.
Jian Tang, Yadong He, Hongfei Chen, Wangjian Sheng, and Huan Wang*, Synthesis of bioactive and stabilized cyclic peptides by macrocyclization using C(sp3)-H activation, Chem. Sci. 2017, 8, 4565-4570.
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