Amir Hoveyda

Biography

Amir Hoveyda is the director of the Catalysis in Chemical Synthesis laboratory at the Institute of Supramolecular Science and Engineering (ISIS) at the University of Strasbourg and French National Centre for Scientific Research (CNRS), and also the Patricia and Joseph T. ’49 Vanderslice Millennium Professor of Chemistry at Boston College in the United States. His research interests, while wide ranging, are centered on catalysis.

He has made notable contributions to the development of catalysts and catalytic strategies for stereoselective olefin metathesis as well as enantioselective conjugate additions, allylic substitutions and additions of modifiable moieties to challenging electrophiles (such as ketones and ketimines). The work by the Hoveyda group is characterized by extensive mechanistic investigations and use of the resulting technology and understanding to total synthesis of complex bioactive natural products. More recent areas of research include the development of catalytic multicomponent processes for precise framework editing of bioactive molecules, and design of new catalytic and bioorthogonal click processes.

Professor Hoveyda received his undergraduate degree at Columbia University and his PhD at Yale University. He was a National Institutes of Health (NIH) and an American Cancer Society postdoctoral fellow at Harvard University. He has received a United States NIH MERIT award (2005), the Yamada-Koga Prize (2010), the American Chemical Society (ACS) Award for Creative Work in Synthetic Organic Chemistry (2014), the Eni Award for Hydrocarbon Research (2014), and the ACS Herbert C. Brown Award for Creative Research in Synthetic Methods (2020). Professor Hoveyda is a co-founder of XiMo, AG (now a subsidiary of Verbio, AG).

Fellowship 2025

Dates - 01/09/2025-31/08/2027

Project summary

CATALYTIC STAPLING AND ROS-TRIGGERED DE-STAPLING OF PEPTIDES

Click chemistry has transformed every branch of chemistry, from chemical synthesis and materials research to biological chemistry and drug development. Nevertheless, major shortcomings remain unaddressed. There is a pressing need for new click reactions with the following features: (i) capable of connecting two fragments, regardless of their size and structure, through a pair of easy-to-install and robust functional groups; (ii) tolerant of a wide range of polar and protic moieties; (iii) proceed readily in aqueous media groups (both often deactivate/react with organometallic species), ensuring applicability in a biological setting; (iv) generate connectors that offer a crucial function, such as light sensitivity, binding ability and/or cleavability. There are no existing click reactions that directly generate controllably cleavable linkage; (v) are mutually orthogonal to the existing click reactions, allowing their use in combination. The proposed studies will deliver a click strategy that satisfies the above requirements.

The USIAS Fellowship will allow the Hoveyda group in Strasbourg to apply a click reaction recently developed by them, namely Cu(I)-catalyzed allene-ketone addition (CuAKA), for stapling of bioactive peptides. CuAKA can be used in water to functionalize peptides in their unprotected form and is mutually orthogonal to CuAAC (Cu(I)-catalyzed azide-alkyne cycloaddition) and SuFEx (sulfur-fluoride exchange), the two most widely used catalytic click reactions. Equally important, the linkages generated can be clipped, causing de-stapling by a process that is triggered by H₂O₂, a reactive oxygen species (ROS), the concentration of which is higher in a cancerous or diabetic cell. Accordingly, cyclic peptides of different ring sizes - a class of compounds of considerable interest in therapeutic science - will become easily accessible. What is more, these macrocycles, which are more robust and penetrate cell membranes more easily, can be de-stapled after entering an unhealthy cell to reveal a peptide’s more active linear form. Thus, overall, the approach will be applicable to applications in directed multi-drug delivery.