Research directions：

1. Biomolecule responsive polymers and bio-applications

Life systems strongly rely on biomolecular interactions, such as DNA-protein, antibody-antigen, protein-glycan, protein-drug interactions, to perform various bio-functions, which further modulate a wide variety of cellular behaviors. Precise molecular recognition and highly specific interaction between two biomolecules are the basis and prerequisite for biomolecules performing their bio-functions. Through learning and mimicking the specific biomolecule interactions, and integrating the conformational transition of smart polymer chains, a series of biomolecule-responsive polymers could be developed, which well satisfies the high demands of “Precision Medicine”, also called “Individual Therapy”. Owing to the substantially higher recognition and capture efficiency of the materials, biomolecule-responsive polymers and corresponding devices will find broad applications in bio-separation, bio-analysis, controllable drug release, biochips, protein conformational modulation and tissue engineering. This direction integrates multiple research fields, including smart polymer, host-guest chemistry, micro-/nano-devices, precise measurement, biochemistry, medicine, we anticipate that it would grow up into a hot research topic in the near future. Ref: Qing, et al. Biomolecule Responsive Polymers and Bio-applications, Prog. Polym. Sci. 2019, invited review.

 

2. Smart enrichment materials for post-translational modification (PTM) proteomics；

PTM-proteomics is one of the leading edge and hot research topics in the fields of biology and medicine. Owing to powerful capture capacities of phosphorylated peptide or glycosylated peptide enrichment materials, the research of protein phosphorylation and glycosylation develop rapidly, discovering a series of cellular signal pathways that are closely related to cell apoptosis, tumorigenesis, immune response and neurodegenerative diseases, which provide solid supports for the early diagnosis of disease, effective treatment and target drug development.

However, except for the well-known protein phosphorylation and glycosylation, there are more than three hundred PTM types, including the most typical ones, such as methylation, acetylation, ubiquitination and others. The capture of these PTM-proteins or peptides strongly relies on antibodies, which usually suffer from low enrichment efficiency, high cost and easier deactivation. The lack of high-efficiency artificial materials severely constrains related research. Therefore, the development of precise enrichment materials, particularly those based on biomolecule-responsive polymers, will have broad application prospects, capable of providing a series of powerful material tools for in-depth biological and medical research. Ref: Qing, et al. New Opportunities and Challenges of Smart Polymers in Post-Translational Modification Proteomics, Adv. Mater. 2017, 29, 1604670.

 

3. Precise glycan capture and analysis

Carbohydrates, glycoproteins and glycoconjugates widely exist in living system and play vital roles in numerous biochemical processes. In addition to the well-known roles of glucose as fundamental energy source of living cells and intermediate products of metabolism, glycoprotein has been discovered to participate in most life processes, including protein folding, stability and transport of proteins, mediation of inflammatory response, regulation of leukocyte cell adhesion, control of angiogenesis and blood clotting. Glycosylation is one of the most common and important types of protein post-translational modifications in mammalian cells. Subtle alteration of one monosaccharide in immunoglobulin G (IgG) glycan might remarkably change the glycoproteins’ biological functions. Increasing evidence has proved that altered or abnormal expression of glycans on glycoproteins is closely related to many diseases, such as oncogenesis, cancer transformation and progression. Importantly, more than 50% of cancer biomarkers used in clinical diagnosis are glycoproteins, for examples, alpha-fetoprotein (CA 125) and mucin epitopes (CA15-3). Thus, the exploration and discovery of protein glycosylation has become a new interdisciplinary research of chemistry, biology and biopharmaceuticals.

Glycans contain an abundance of information owing to their complex carbohydrate composition, different branched structures and linkage types, which constitute a mysterious “glycoworld”. However, it is extraordinarily challenging to analyze the mysterious “glycoworld”, which requires the identification of both glycosylation sites and glycan structures simultaneously. To decode the glycoworld, it is highly important to enrich glycopeptides or separate glycans with low abundance from complex biosamples, which requires the development of various glycopeptide or glycoprotein enrichment materials and tools. In addition, the analysis of delicate structures of glycans is more challenging, which strongly relies on the combination of high resolution MS and two-dimensional NMR, sufficient glycan samples with high purity and well trained analysts are needed urgently. We are devoting our efforts to develop various advanced glycan-specific materials and devices to solve this puzzle problem of glycan analysis and decoding. Ref: Qing, et al. Recent Advances in Hydrophilic Interaction Liquid Interaction Chromatography Materials for Glycopeptide Enrichment and Glycan Separation, TrAC Trends in Anal. Chem. 2019, invited review.

 

4. Smart bio-separation materials

Tremendous advance of life science and biotechnology industry has raised the higher requirement for conventional bio-separation. Currently, chromatographic and related separation techniques have been refined to such a degree that they present efficient separation capacity towards complex samples in fields like pharmaceuticals, proteomics, and food industry etc. However, new breakthroughs, including higher selectivity, more controllable separation mode, lower cost, and mild operation conditions, in various affinity separation techniques are still highly desirable in complicated application scenarios. Smart materials, particularly stimuli-responsive polymer, which could reversibly change their structures and properties in response to the external stimuli provide an ideal solution to upgrade conventional separation strategies, and endow them with smart traits, which is, regulating the affinity between the analyte and separation matric to achieve the controlled capture and release of the analyte of interest.

In general, the entire bio-separation process involves in a series of variables, including mass transfer, surface wettability, solid-liquid partitioning, conformation matching and binding affinity, which directly influence the separation performance, and even determine the success or not in separation. This provides us broad space to upgrade the conventional separation strategies and endow them with intelligent traits, and to further improve the separation performance in more complicated application scenarios. Despite considerable progress has been witnessed over the past few years, there are still some opportunities and challenges ahead for the development of smart bio-separation materials. Ref: Qing, et al. Smart Bio-Separation Materials, TrAC Trends in Anal. Chem. 2019, invited review.

 

5. Discovery of chiral effect

Chirality is one of most typical characteristics of living system, chiral molecules and chiral effects are ubiquitous in the world, from the single molecular chirality, helical chirality of helical polymers, proteins and DNA, anisotropic directions at the macroscopic level, to helicoidal nebula in the universe. Discovery of the origin of chirality, chiral assembly and chiral amplification is one of the 25 most important scientific problems in the 21^st century. Meanwhile, taking advantages of the stereoselective interactions between two biomolecules, a series of biomolecule precise recognition materials could be developed. Weak chiral recognition signals could be captured, transferred and amplified into macroscopic property changes of the materials. It will be very interesting to discover fantastic chiral effects, to observe delicate chiral interactions, and to construct various chiral molecule-sensitive devices. Ref: Qing, et al. The Transformation of Chiral Signals into Macroscopic Properties of Materials Using Chirality-Responsive Polymers, NPG Asia Materials, 2012, 4, E4.

   

[1] Yuting Xiong, Xiuling Li, Minmin Li, Haijuan Qin, Cheng Chen, Dongdong Wang, Xue Wang, Xintong Zheng, Yunhai Liu, Xinmiao Liang,* Guangyan Qing,* What is hidden behind schiff base hydrolysis? Dynamic covalent chemistry for the precise capture of sialylated glycans. J. Am. Chem. Soc. 2020, DOI: 10.1021/jacs.0c01970.

[2] Minmin Li, Yuting Xiong, Xinmiao Liang,* Guangyan Qing,* Biomimetic nanochannels for the discrimination of sialylated glycans via a tug-of-war between glycan binding and polymer shrinkage. Chemical Sciences, 2020, 11, 748–756.

[3] Guangyan Qing, Qi Lu, Jing Liu, Mingliang Ye, Xiuling Li,* Xinmiao Liang,* Taolei Sun*, Hydrogen bond based smart polymer for highly selective and tunable capture of multiply phosphorylated peptides. Nature Commun. 2017, 8, 461.

[4] Guangyan Qing, Taolei Sun,* et al. New opportunities and challenges of smart polymers in post-translational modification proteomics. Adv. Mater. 2017, 29, 1604670.

[5] Guangyan Qing,* Shiliong Zhao, Taolei Sun,* et al. Chiral effect at protein/ graphene interface: A bioinspired perspective to understand amyloid formation. J. Am. Chem. Soc. 2014, 136 (30), 10736–10742.

[6] Guangyan Qing, Xingxing Shan, Taolei Sun,* et al. Solvent-driven chiral-interaction reversion for organogel formation. Angew. Chem. Int. Ed. 2014, 53 (8), 2124–2129.

[7] Guangyan Qing, Taolei Sun.* Chirality-driven wettability switching and mass transfer. Angew. Chem. Int. Ed. 2014, 53 (4), 930–932.

[8] Guangyan Qing, Taolei Sun.* Transforming chiral signals into macroscopic properties of materials using chirality-responsive polymers. NPG: Asia Materials 2012, 4, e4.

[9] Guangyan Qing, Taolei Sun.* Chirality triggered wettability switching on smart polymer surface. Adv. Mater. 2011, 23 (14), 1615–1620.

[10] Guangyan Qing, Hai Xiong, Frank Seela,* Taolei Sun.* Spatially controlled DNA nanopatterns by “click” chemistry using oligonucleotides with different anchoring sites. J. Am. Chem. Soc. 2010, 132 (43), 15228–15232.

[11] Guangyan Qing, Xing Wang, Harald Fuchs, Taolei Sun.* Nucleotide responsive wettability on smart polymer surface. J. Am. Chem. Soc. 2009, 131 (24), 8370–8371.

[12] Guangyan Qing, et al. Biomolecule responsive polymers: From biomolecule recognition to applications in post-translational modification proteomics. Chem. Soc. Rev. 2020，invited review.

[13] Zhonghui Chen, Guangyan Qing,* Taolei Sun,* et al. A biomimetic design for sialylated glycan-specific smart polymer. NPG Asia Materials 2018, 10, e472.

[14] Shengyan Ji, Guangyan Qing,* et al. cAMP sensitive nanochannels driven by conformational transition of a tripeptide-based smart polymer. Chem. Commun. 2020, 56, 3425–3428.

[15] Qi, Lu, Xiuling Li,* Guangyan Qing,* High-efficiency phosphopeptide and glycopeptide simultaneous enrichment by hydrogen bond−based bifunctional smart polymer. Anal. Chem. 2020, DOI: 10.1021/acs.analchem.9b02643.

[16] Zhonghui, Chen,* Ziyu Lv, Yifeng Sun, Zhenguo Chi,* Guangyan Qing,* Recent advancements in polyethyleneimine-based materials and their biomedical, biotechnology, and biomaterial applications. J. Mater. Chem. B 2020, DOI: 10.1039/c9tb02271f.

[17] Zhixiang, Taolei Sun, Guangyan Qing,* CAMP-modulated biomimetic ionic nanochannels based on smart polymer. J. Mater. Chem. B 2019, 7, 3710–3715.

[18] Yunlong Li, Guangyan Qing,* et al. Developing a calcium-actuated ionic nanochannel system by mimicking biological Ca²⁺-induced Ca²⁺ release process. NPG Asia Materials 2019, 11, 46.

[19] Xiaofei Zhang, Xiuling Li,* Guangyan Qing,* et al. Smart polymers driven by multiple and tunable hydrogen bonds for intact phosphoprotein enrichment. Sci. Tech. Adv. Mater. 2019, 20, 858–869.

[20] Kenan Shao, Guangyan Qing,* et al. Circularly polarized light modulated supramolecular self-assembly for azobenzene-based chiral gel. RSC Adv. 2019, 9, 10360-10363.

现指导学生

杨航  博士研究生  070302-分析化学  

逯文启  硕士研究生  070302-分析化学  

宋梦圆  硕士研究生  070302-分析化学