phone 716-645-4254

Welcome to the Lin Lab

Our research aims to develop and apply new chemical tools and principles to solve biological problems that are difficult to solve, if not impossible, by standard biological techniques. A central theme of our research is to harness the power of organic reactions to study protein dynamics, function, and protein-protein interactions and their assembly in living organisms. Currently, our research efforts focus on the following three areas:

1. Development of bioorthogonal reactions as a tool to study spatiotemporal regulation of protein functions in various cellular systems;

2. Development of new chemistries for translating bioactive peptides into human cancer therapeutics; and

3. Heterologous expression of protein-based bacterial microcompartments in yeast for metabolic production of novel chemicals, e.g., high-energy transportable biofuels.

Bioorthogonal Chemistry

In the post-genomic era, there is an increasing desire to study the dynamics and function of biomolecules in their native environments in living cells and organisms. To this end, bioorthogonal chemistry has emerged as a general strategy for the study of biomolecular dynamics and function in living systems. Compared with the noncovalent binding-based approach, bioorthogonal chemistry relies upon a specific, covalent attachment of a probe molecule to the biomolecule(s) of interest. Over the past few years, we have developed several bioorthogonal reactions, most notably, a photoinduced tetrazole-alkene cycloaddition reaction (“photoclick chemistry”) and a palladium-mediated cross-coupling reaction, for protein labeling in vitro and in vivo.  Our current efforts are geared toward the application of bioorthogonal chemistry to understand the conformational dynamics of the class B G-protein coupled receptors in living cells.

Enabling Chemistries for Peptide-Based Therapeutics

α-Helix is one of the most common protein secondary structures and frequently found at the interfaces of protein-protein interactions, regulating a diverse range of cellular processes. While short peptides may exhibit potent in vitro activity and are generally devoid of toxicity, they rarely are good therapeutic candidates because of their unfavorable pharmacological properties, e.g., low proteolytic stability and inefficient cellular uptake. To overcome these limitations, peptide stapling―the cross-linking of peptide side chains―has emerged as a promising strategy in directly translating bioactive peptides into therapeutics. We have reported a class of distance-matching biaryl cross-linkers for efficient stapling of the cysteine-containing bioactive peptides. In collaboration with the cancer biologists, we are actively applying our stapling chemistries to develop the peptide-based cancer therapies.

Orthogonal Microcompartments for Biofuels Production

Inspired by marvelous efficiency of the naturally occurring, protein-based bacterial microcompartment (BMC) in executing the specialized metabolic cascade reactions, e.g., CO2 fixation, we envision that these nanosized BMCs can be heterologously expressed in Saccharomyces cerevisiae and serve as orthogonal, amplifiable intracellular bioreactors for the engineered metabolic pathways, e.g., the biofuel production pathways. In this synthetic biology project, our objectives are twofold: reconstitute intact Escherichia coli ethanolamine utilization (Eut) microcompartment in S. cerevisiae through heterologous expression of the Eut shell proteins; and functionalize the synthetic organelles in S. cerevisiae by fusing the necessary metabolic enzymes either directly with the appropriate shell proteins or to the microcompartment-targeting sequences.











MARCO PAOLO JACINTO, MS (2015-2016), Graduate student, Johns Hopkins University, Baltimore, MD

DAVID SHIM, MS (2014-2016)

Dr. ANDRÁS HERNER, Postdoc (2015-2016), Team leader, Petér Kele group, Hungarian Academy of Sciences, Budapest, Hungary

Dr. ZHIPENG YU, Postdoc (2009-2015), Professor, Sichuan University, China

Dr. GANG CHENG, Postdoc (2012-2014), Instructor, Zhejiang University, China

AVINASH MUPPIDI, PhD (2009-2014), Scientist, Eli Lilly and Company, Indianapolis, IN

REYNA KOREEN V. LIM, PhD (2007-2013), Scientist, Sorrento Therapeutics, San Diego, CA

DIFEI JIANG, MS (2011-2013), Chemist, CS Bio Co., Menlo Park, CA

Dr. NAN LI, Postdoc (2009-2012), Associate Professor, Shaanxi Normal University, China

LOK Y. HO, MS (2008-2011)

Dr. SELVAKUMAR EDWARDRAJA, Postdoc (2010-2011), Postdoc w/ Dr. Arne Skerra, Technical University of Munich

Dr. ZHIYONG WANG, Postdoc (2009-2010), Associate Professor, Chongqing University, China

YIZHONG WANG, PhD (2006-2010), Postdoc w/ Prof. Joseph Ready, UT Southwestern

MICHAEL M. MADDEN, PhD (2005-2010), Assistant Professor, Lake Erie College of Osteopathic Medicine, Erie, PA

WENJIAO SONG, PhD (2005-2010), Scientist, Teva Pharmaceutical Industries

CLAUDIA RIVERA VERA, MS (2005-2009), Graduate student, University of Illinois at Chicago


LINDSAY SWAYZE, 2007, PhD, Roswell Park Cancer Institute

WARREN CHOI, 2007, MD, Georgetown University


JOEL URENA, 2007, MD, SUNY Buffalo

WEN J. HU, 2008


JIANLE XIE, 2009, PharmD, SUNY Buffalo

ZHEN REN, 2011



DANIEL ROTSHTEYN, 2012, PhD, SUNY Buffalo Chemistry

NABIHA AHSAN, 2014, MD, SUNY Buffalo




57. András Herner, Jasmina Marjanovic, Tracey M. Lewandowski, Violeta L. Marin, Melanie J Patterson, Laura Miesbauer, Damien Ready, Jon Williams, Anil Vasudevan*, and Qing Lin*
"2-Aryl-5-carboxytetrazole as a New Photoaffinity Label for Drug Target Identification"
J. Am. Chem. Soc., 2016, 138, 14609–14615.

56. Carlo P. Ramil, Peng An, Zhipeng Yu, and Qing Lin*
"Sequence-specific 2-cyanobenzothiazole ligation"
J. Am. Chem. Soc., 2016, 138, 5499–5502.

55. Avinash Muppidi, Huafei Zou, Peng Yu Yang, Elizabeth Chao, Lance Sherwood, Vanessa Nunez, Ashley K. Woods, Peter G. Schultz*, Qing Lin*, and Weijun Shen*
"Design of Potent and Proteolytically Stable Oxyntomodulin Analogs"
ACS Chem. Biol., 2016, 11, 324–328.

54. András Herner and Qing Lin*
"Photo-Triggered Click Chemistry for Biological Applications" in "Cycloadditions in Bioorthogonal Chemistry"
Top. Curr. Chem., 2016, 374, 1.

53. Alford A. John, Carlo P. Ramil, Yulin Tian, Gang Cheng and Qing Lin*
"Synthesis and Site-Specific Incorporation of Red-Shifted Azobenzene Amino Acids into Proteins"
Org. Lett., 2015, 17, 6258-6261.

52. Nan Li, Carlo P. Ramil, Reyna K.V. Lim, and Qing Lin*
"A Genetically Encoded Alkyne Directs Palladium-Mediated Protein Labeling on Live Mammalian Cell Surface"
ACS Chem. Biol., 2015, 10, 379-384.

51. Gang Cheng, Reyna K.V. Lim, Carlo P. Ramil, and Qing Lin*
"Storable N-Phenylcarbamate Palladacycles for Rapid Functionalization of An Alkyne-Encoded Protein"
Chem. Commun., 2014, 50, 11679-11682.

50. Reyna K.V. Lim, Nan Li, Carlo P. Ramil and Qing Lin*
"Fast and sequence-specific palladium-mediated cross-couping reaction identified from phage display"
ACS Chem. Biol., 2014, 9, 2139–2148.

Highlighted in Chem. Eng. News, July 28, 2014. “Phage display finds bioorthogonal chemistry”

49. Carlo P. Ramil and Qing Lin*
"Photoclick chemistry: a fluorogenic light-triggered in vivo ligation reaction"
Curr. Opin. Chem. Biol., 2014, 21, 89-95. (Review Article)


48. Avinash Muppidi, Kenichiro Doi, Carlo P. Ramil, Hong-Gang Wang, and Qing Lin*
"Synthesis of cell-permeable stapled BH3 peptide-based Mcl-1 inhibitors containing simple ary and vinylaryl cross-linkers"
Tetrahedron, 2014, 70, 7740–7745.


47. Avinash Muppidi, Hongtao Zhang, Francesca Curreli, Nan Li, Asim K. Debnath and Qing Lin*
"Design of antiviral stapled peptides containing a biphenyl cross-linker"
Bioorg. Med. Chem. Lett., 2014, 24 (7), 1748-1751.


46. Zhipeng Yu and Qing Lin*
"Design of Spiro[2.3]hex-1-ene, a Genetically Encodable Double-Strained Alkene for Superfast Photoclick Chemistry"
J. Am. Chem. Soc., 2014, 136 (11), 4153-4156.








45. Avinash Muppidi, Kenichiro Doi, Selvakumar Edwardraja, Surya V. S. R. K. Pulavarti, Thomas Szyperski, Hong-Gang Wang, and Qing Lin*
"Targeted delivery of ubiquitin-conjugated BH3 peptide-based Mcl-1 inhibitors into cancer cells"
Bioconjugate Chem., 2014, 25 (2), 424-432.


44. Zhipeng Yu, Tymish Y. Ohulchanskyy, Peng An, Paras N. Prasad, and Qing Lin*
"Fluorogenic Two-Photon-Triggered Photoclick Chemistry in Live Mammalian Cells"
J. Am. Chem. Soc., 2013, 135 (45), 16766-16769.



43. Carlo P. Ramil and Qing Lin*
"Bioorthogonal chemistry: strategies and recent developments"
Chem. Commun., 2013, 49 (94), 11007-11022. (Feature Article)


42. Peng An, Zhipeng Yu, and Qing Lin*
"Design and synthesis of laser-activatable tetrazoles for a fast and fluorogenic red-emitting 1,3-dipolar cycloaddition reaction"
Org. Lett., 2013, 15 (21), 5496-5499.


41. Peng An, Zhipeng Yu, and Qing Lin*
"Design of oligothiophene-based tetrazoles for laser-triggered photoclick chemistry in living cells"
Chem. Commun., 2013, 49, 9920-9922.


40. Gang Cheng, Reyna K.V. Lim, Nan Li, and Qing Lin*
"Storable palladacycles for selective functionalization of alkyne-containing proteins"
Chem. Commun., 2013, 49, 6809-6811.


39. Avinash Muppidi, Kenichiro Doi, Selvakumar Edwardraja, Eric J. Drake, Andrew M. Gulick, Hong-Gang Wang, and Qing Lin*
"Rational design of proteolitically stable, cell-permeable peptide-based selectice Mcl-1 inhibitors"
J. Am. Chem. Soc., 2012, 134, 14734-14737.

Recommended by Faculty of 1000 Pharmacology & Drug Discovery, September 27, 2012


38. Zhipeng Yu, Yanchao Pan, Zhiyong Wang, Jiangyun Wang*, and Qing Lin*
"Genetically Encoded Cyclopropene Directs Rapid, Photoclick Chemistry-Mediated Protein Labeling in Mammalian Cells"
Angew. Chem. Int. Ed., 2012, 51, 10600-10604.


37. Avinash Muppidi, Xiaolong Li, Jiandong Chen, and Qing Lin*
"Conjugation of Spermine Enhances Cellular Uptake of Stapled Peptide-Based Inhibitors of p53-Mdm2 Interaction"
Bioorg. Med. Chem. Lett., 2011, 21, 7412-7415.


36. Nan Li, Reyna K. V. Lim, Selvakumar Edwardraja, and Qing Lin*
"Copper-Free Sonogashira Cross-Coupling for Functionalization of Alkyne-Encoded Proteins in Aqueous Medium and in Bacterial Cells"
J. Am. Chem. Soc., 2011, 133, 15316-15319.


35. Avinash Muppidi, Zhiyong Wang, Xiaolong Li, Jiandong Chen and Qing Lin*
Achieving Cell Penetration with Distance-Matching Cysteine Cross-Linkers: A Facile Route to Cell-Permeable Peptide Dual Inhibitors of Mdm2/Mdmx
Chem. Commun., 2011, 47, 9396-9398.


34. Zhipeng Yu, Lok Yin Ho and Qing Lin*
Rapid, Photoactivatable Turn-On Fluorescent Probes Based On an Intramolecular Photoclick Reaction
J. Am. Chem. Soc., 2011, 133, 11912-11915.


33. Reyna K. V. Lim and Qing Lin*
Photoinducible Bioorthogonal Chemistry: A Spatiotemporally Controllable Tool to Visualize and Perturb Proteins in Live Cells
Acc. Chem. Res., 2011, 44, 828-839.


32. Zhipeng Yu, Lok Yin Ho, Zhiyong Wang and Qing Lin*
Discovery of New Photoactivatable Diaryltetrazoles for Photoclick Chemistry via 'Scaffold Hopping'”
Bioorg. Med. Chem. Lett., 2011, 21, 5033-5036.


31. Michael M. Madden, Avinash Muppidi, Zhenyu Li, Xiaolong Li, Jiandong Chen,* and Qing Lin*
Synthesis of Cell-Permeable Stapled Peptide Dual Inhibitors of the p53-Mdm2/Mdmx Interactions via Photoinduced Cycloaddition
Bioorg. Med. Chem. Lett., 2011, 21, 1472-1475.


30. Wenjiao Song and Qing Lin*
In Vitro and In Vivo Screening: Methods of High-throughput Screening
in Protein Surface Recognition: Approaches for Drug Discovery, Giralt, E., Peczuh, M., Salvatella, X. Ed. Wiley-VCH, 2011, 251-271.


29. Zhipeng Yu, Reyna K. V. Lim, and Qing Lin*
"Synthesis of Macrocyclic Tetrazoles for a Photoinduced, Bioorthogonal 1,3-Dipolar Cycloaddition Reaction"
Chem. Eur. J., 2010, 16, 13325-13329.

28. Jiangyun Wang*, Wei Zhang, Wenjiao Song, Yizhong Wang, Zhipeng Yu, Jiasong Li, Minhao Wu, Lin Wang, Jianye Zang, and Qing Lin*
"A Biosynthetic Route to Photoclick Chemistry on Protein"
J. Am. Chem. Soc., 2010, 132, 14812-14818.


27. Reyna K. V. Lim and Qing Lin*
"Azirine Ligation: Fast and Selective Protein Conjugation via Photoinduced Azirine-Alkene Cycloaddition"
Chem. Commun., 2010, 46, 7993-7995.


26. Wenjiao Song, Yizhong Wang, Zhipeng Yu, Claudia I. Rivera Vera, Jun Qu, and Qing Lin*
"A Metabolic Alkene Reporter for Spatiotemporally Controlled Imaging of Newly Synthesized Proteins in Mammalian Cells"
ACS Chem. Biol., 2010, 5, 875-885. (Cover Article)
Evaluated by Faculty of 1000 Biology as "Must Read", October 14, 2010


25. Wenjiao Song, Zhipeng Yu, Michael M. Madden, and Qing Lin*
"A Bioorthogonal Chemistry Strategy for Probing Protein Lipidation in Live Cells"
Mol. Biosys., 2010, 6, 1576-1578.


24. Reyna K. V. Lim and Qing Lin*
"Bioorthogonal Chemistry: Recent Progress and Future Directions"
Chem. Commun., 2010, 46, 1589-1600. (Feature Article)


23. Reyna K. V. Lim and Qing Lin*
"Bioorthogonal Chemistry: A Covalent Strategy for the Study of Biological Systems"
Science China: Chemistry, 2010, 53, 61-70.


22. Shao-Liang Zheng, Yizhong Wang, Zhipeng Yu, Qing Lin*, and Philip Coppens
"Direct Observation of a Photoinduced Nonstabilized Nitrile Imine Structure in the Solid State"
J. Am. Chem. Soc., 2009, 131, 18036-18037.


21. Michael M. Madden, Claudia I. Rivera Vera, Wenjiao Song, and Qing Lin*
"Facile Synthesis of Stapled, Structurally Reinforced Peptide Helices via A Photoinduced Intramolecular 1,3-Dipolar Cycloaddition Reaction"
Chem. Commun., 2009, 5588-5590.


20. Yizhong Wang and Qing Lin*
"Synthesis and Evaluation of Photoreactive Tetrazole Amino Acids"
Org. Lett., 2009, 3570-3573.


19. Yizhong Wang, Wenjiao Song, Wen J. Hu, and Qing Lin*
"Fast Alkene Functionalization In Vivo by Photoclick Chemistry: HOMO-Lifting of Nitrile Imine Dipoles"
Angew. Chem. Int. Ed., 2009, 48, 5330-5333.

Highlighted in Nature Chemical Biology , August 2009 issue.



18. Qing Lin*, and Reyna K. V. Lim
"Traceless Native Protein Labeling In Mice"
Nat. Chem. Biol., 2009, 5, 275-276. (News & Views Article)


17. Yizhong Wang , Wen J. Hu , Wenjiao Song , Reyna K. V. Lim and Qing Lin*
"Discovery of Long-Wavelength Photoactivatable Diaryltetrazoles for Bioorthogonal 1,3-Dipolar Cycloaddition Reactions"
Org. Lett., 2008, 10 (17), pp 3725–3728.


16. Wenjiao Song, Yizhong Wang, Jun Qu, and Qing Lin*
"Selective Functionalization of a Genetically Encoded Alkene-Containing Protein via “Photoclick Chemistry” in Bacterial Cells"
J. Am. Chem. Soc., 2008, 130, 9654-9655.

Featured in C&EN Science & Technology Concentrates, July 14 Issue.
Highlighted in ACS Chemical Biology Spotlight, September 15 issue.
Highlighted in Angew. Chem. Int. Ed. 2009, 48, 1729-1731.



15. Wenjiao Song, Yizhong Wang, Jun Qu, Michael M. Madden, and Qing Lin*
"A Photoinducible 1,3-Dipolar Cycloaddition Reaction for Rapid, Selective Modification of Tetrazole-Containing Proteins"
Angew. Chem. Int. Ed., 2008, 47, 2832-2835.

Recommended by Faculty of 1000 Biology, March 25, 2008.
Highlighted in Angew. Chem. Int. Ed. 2009, 48, 1729-1731.



14. Michael M. Madden, Wenjiao Song, Paul G. Martell, Yong Ren, Jian Feng, and Qing Lin*
"Substrate Properties of Ubiquitin Carboxyl-Terminally Derived Peptide Probes for Protein Ubiquitination"
Biochemistry, 2008, 47, 3636-3644.


13. Yizhong Wang, Claudia Rivera Vera, and Qing Lin*
"Convenient Synthesis of Highly Functionalized Pyrazolines via Mild, Photoactivated 1,3-Dipolar Cycloaddition"
Org. Lett., 2007, 9, 4155-4158.


12. Jiazhi Sun, Michelle Blaskovich, Rishi K. Jain, Frederic L. Delarue, Daniel Paris, Steven Brem, Marguerite Wotocezk-Obadia, Qing Lin, Domenico Coppola, Kihang Choi, Michael Mullan, Andrew D. Hamilton and Saïd M. Sebti
"Blocking Angiogenesis and Tumorigenesis with GFA-116, a Synthetic Molecule that Inhibits Binding of Vascular Endothelial Growth Factor to its Receptor"
Cancer Res., 2004, 64, 3586-3592.

11. Qing Lin, Carlos F. Barbas III and Peter G. Schultz*
"Small Molecule Switches for Zinc Finger Transcription Factors"
J. Am. Chem. Soc., 2003, 125, 612-613.

10. Qing Lin and Andrew D. Hamilton*
"Design and synthesis of multiple-loop receptors based on a calix[4]arene scaffold for protein surface recognition"
C. R. Chimie, 2002, 5, 441-450.

9. Hyung Soon Park, Qing Lin, and Andrew D. Hamilton*
"Modulation of protein–protein interactions by synthetic receptors: Design of molecules that disrupt serine protease–proteinaceous inhibitor interaction"
PNAS, 2002, 99, 5105-5109.

8. Qing Lin, Fanyi Jiang, Peter G. Schultz* and Nathanael Gray*
"Design of Allele-Specific Protein Methyltransferase Inhibitors"
J. Am. Chem. Soc., 2001, 123, 11608-11613.

7. Yen Wei*, George L. McLendon*, Andrew D. Hamilton*, Martin A. Case, Cherie B. Purring, Qing Lin, Hyung Soon Park, Chang-Sun Lee and Tianning Yu
"Disruption of Protein-Protein Interactions: Design of A Synthetic Receptor that Blocks the Binding of Cytochrome c to Cytochrome c Peroxidase"
Chem. Commun., 2001, 1580-1581.

6. Michelle Blaskovich, Qing Lin, Frederic L. Delarue, Jiazhi Sun, Domenico Coppola, Hyung Soon Park, Andrew D. Hamilton and Saïd M. Sebti
"Design of GFB-111 a Platelet-Derived Growth Factor Binding Molecule with Anti-Angiogenic and Anti-Cancer Activity Against Human Tumors in Mice"
Nature Biotechnol., 2000, 18, 1065-1070.


5. Hyung Soon Park, Qing Lin and Andrew D. Hamilton*
"Protein Surface Recognition by Synthetic Receptors: A Route to Novel Sub-micromolar Inhibitors for α-Chymotrypsin"
J. Am. Chem. Soc., 1999, 121, 8-13.

4. Qing Lin, Hyung Soon Park, Yoshitomo Hamuro, and Andrew D. Hamilton*
"Protein Surface Recognition by Synthetic Receptors"
in Supramolecular Science: Where It Is and Where It Is Going, Ungaro, R., Dalcanale, E. Ed. Kluwer, Amsterdam, 1999, 197-204.

3. Andrew D. Hamilton, Hyung Soon Park, Qing Lin and Rishi Jain
"Towards Artificial Antibodies: Protein Surface Recognition by Synthetic Receptors"
in Peptides for the New Millennium, Fields, G.B.; Tam, J.P.; Barany, G. Eds., Kluwer, Dordrecht, 1999, 531-533.

2. Qing Lin, Hyung Soon Park, Yoshitomo Hamuro, Chang-Sun Lee and Andrew D. Hamilton*
"Protein surface recognition by synthetic agents: Design and structural requirements of a family of artificial receptors that bind to cytochrome C"
Biopolymers (Peptide Science), 1998, 47, 285-297.

1. Qing Lin, Steven J. Geib and Andrew D. Hamilton*
"1-Phenyl-1H-pyrrole-2,5-dicarboxylic acid derivatives asversatile hydrogen-bonding motifs for the formation of one-, two- andthree-dimensional networks in the solid state"
J. Chem. Soc., Perkin Trans. 2, 1998, 2109-2116.






icon 1 679 Natural Sciences Complex, Department of Chemistry, University at Buffalo, Buffalo NY 14260

icon 2 (716) 645-4254 Fax: (716) 645-6963

icon 3

One of the beautiful things about science is that it allows us to bumble along, getting it wrong time after time, and feel perfectly fine as long as we learn something each time.