A. James Link

Professor of Chemical and Biological Engineering
Phone: 
609-258-7191
Email Address: 
ajlink@Princeton.EDU
Assistant: 
Office Location: 
207 Hoyt Laboratory
Degrees: 

Ph.D.,Chemical Engineering, California Institute of Technology, 2006

M.S., Chemical Engineering, California Institute of Technology, 2002

BSE, Chemical Engineering, Princeton University, 2000

Honors and Awards

  • Participant in German-American Frontiers of Science Symposium, 2016
  • Participant in NAE US/EU Frontiers of Engineering, 2014
  • Alfred P. Sloan Research Fellowship (Chemistry), 2013-2015
  • DuPont Young Professor, 2011
  • NSF CAREER Award, 2010
  • NIH Kirschstein/NRSA Fellowship, 2006
  • NSF Graduate Research Fellowship, 2000
  • Tau Beta Pi Fellowship, 2000

Affiliations

  • Associated Faculty, Andlinger Center for Energy and the Environment
  • Associated Faculty, Department of Chemistry
  • Associated Faculty, Department of Molecular Biology

Research Interests

Since its founding, the Link lab has been interested in applying the tools of protein engineering and bioconjugate chemistry to engineer peptides and proteins with conformational constraints. Conformational constraints within a polypeptide can lead to improvements in properties such as protease stability, thermostability, and binding affinity. With the development of bioorthogonal chemistry in the early 2000’s, the toolbox for conformational constraints expanded. We have used a combination of protein engineering and azide-alkyne click chemistry to carry out “protein stapling” on small proteins (Abdeljabbar et al. Chem. Comm. 2014). We have also used olefin metathesis chemistry to constrain short engineered peptides that function to turn on apoptosis in cells (Link and Zhang, US patent 9,464,125). We have also looked to nature for inspiration in strategies for conformationally constraining peptides. This has led to our program on lasso peptides, an ever expanding class of natural products defined by their slipknot-like topology. Our group started out working on the antimicrobial lasso peptide microcin J25 as an interesting substrate for engineering by directed evolution (Pan et al. JACS 2011) and with unnatural amino acids (Piscotta et al. Chem. Comm 2015). We became interested in the variety of different lasso peptides present in nature and developed the first algorithm for large-scale genome mining of lasso peptides (Maksimov et al. PNAS 2012). We continue to look to lasso peptides as a source of new antibiotics, interesting new enzymology, and even as building blocks for molecular machines.

Publications List: 
  1. Zong C, Wu MJ, Qin JZ, Link AJ: Lasso Peptide Benenodin-1 is a Thermally Actuated [1]Rotaxane Switch. Journal of the American Chemical Society 2017, 139: 10403-10409.
  2. Allen CD, Link AJ: Self-Assembly of Catenanes from Lasso Peptides. Journal of the American Chemical Society 2016, 138: 14214-14217.
  3. Maksimov MO, Link AJ: Discovery and Characterization of an Isopeptidase that Linearizes Lasso Peptides. Journal of the American Chemical Society 2013, 135: 12038-12047.
  4. Maksimov MO, Pelczer I, Link AJ: A Precursor-centric Genome Mining Approach for Lasso Peptide Discovery. Proceedings of the National Academy of Sciences, USA 2012, 109:15223-15228.
  5. Pan SJ, Link AJ: Sequence Diversity in the Lasso Peptide Framework: Discovery of Functional Microcin J25 Variants with Multiple Amino Acid Substitutions. Journal of the American Chemical Society 2011, 133:5016-5023.