1. 天然产物的分离,结构鉴定和化学合成;

2. 天然产物的生物合成;

3. 微生物(包括肠道菌群)的基因组学及生物信息学;

4. 酶化学,酶的改造及定向进化。



General Description
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.

  • Functionalization of Sulfonamide-Containing Peptides through Late-Stage Palladium-Catalyzed C(sp3)–H Arylation

    Bioactive peptides are emerging as promising candidates of clinic therapeutics. Here, we report a method for late-stage functionalization of sulfonamide-containing peptides through Pd-catalyzed C(sp3)–H arylation. In this protocol, the backbones of N-sulfonated peptides act as directing groups, which allows site-specific arylation of benzylsulfonamide moiety. This chemistry exhibits broad substrate scope and can be utilized to synthesize peptide–peptide and peptide–amino acid conjugates. Our results highlight the potency of the backbone of peptidomimetics in promoting Pd-catalyzed functionalization.

  • Characterization of the FMN-Dependent Cysteine Decarboxylase from Thioviridamide Biosynthesis

    The biosynthesis of thioviridamide-like compounds has not been elucidated. Herein, we report that TvaF from the thioviridamide biosynthetic gene cluster is an FMN-dependent cysteine decarboxylase that transforms the C-terminal cysteine of precursor peptides into a thioenol motif and exhibits high substrate flexibility. We resolved the crystal structure of TvaF bound with FMN at 2.24 Å resolution. Key residues for FMN binding and catalytic activity of TvaF have been identified and evaluated by mutagenesis studies.

  • Macrocyclization of peptidoarylacetamides with self-assembly properties through late-stage palladium-catalyzed C(sp2)▬H olefination

    We report the development of a peptide-directed method for the macrocyclization of peptidoarylacetamides by Pd(II)-catalyzed late-stage C(sp2)-H olefination. In this protocol, peptide backbones act as internal directing groups and enable facile preparation of diverse cyclic peptides that are difficult to synthesize by conventional macrolactamization. Furthermore, we show that the incorporation of aryl-alkene cross-link in the backbone constrains cyclic peptides into conformations for self-assembly.

Send emails to Prof. Wang:

School of Chemistry and Chemical Engineering
Nanjing University 
163 Xianlin Avenue, Qixia District, Nanjing, China