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Dr. Raphael Franzini

Raphael Franzini, Ph.D.

Academic Information

Departments College of Pharmacy , Associate Professor - Medicinal Chemistry

Academic Office Information


Research Interests

  • DNA-encoded libraries: Streamlining drug discovery
  • Dissociative Bioorthogonal Chemistry: Activating drugs and probes on demand


DNA-encoded libraries: Streamlining drug discovery

One of the key steps in developing a new drug is to identify molecules that bind to a putative therapeutic target. However, there is a near-unlimited number of possible molecules and to identify the right one is a formidable challenge.

One approach to achieve this goal is to tag compounds with DNA strands whose sequence encodes for the structure of each compounds. In this way it is possible to use target proteins immobilized on surfaces as baits to fish for compounds that bind to this protein. Sequencing the attached DNA codes then allows to identify the corresponding molecules. In fact, this approach provides a semi-quantitative estimation of the target affinity of each compound in the library.

Such DNA-encoded libraries are nowadays used routinely in drug discovery at pharmaceutical companies. However, the prospect of this method remains largely untapped in academic medicinal chemistry efforts because of the costs associated with generating large library platforms and the validation of multiple hit compounds. We aim to overcome this problem by generating libraries that are structurally designed with specific protein families in mind. In this way, we can achieve consistent screening success at a fraction of the costs of large one-fit-all DNA-encoded library platforms.

Using such libraries, we were able to discover high potency hit compounds for several enzymes with speed and cost-efficiency unachievable by conventional methods. In parallel, we aim to further our understanding of how to synthesize and design such library and to develop algorithms for extracting important structural data from such library screens.

Examples of results from DNA-encoded chemical library screens

Examples of results from DNA-encoded chemical library screens. The x/y-axes define the building blocks of a specific compound and thus each sphere is a unique structure. The z-axis indicates the number of obtained sequences after a screen, which is further visually enhanced by the color and size of the sphere. The number of sequences is an indicator of target affinity.
Triple-orthogonal protein labeling using chemistry developed in our group

Triple-orthogonal protein labeling using chemistry developed in our group

Dissociative Bioorthogonal Chemistry: Activating drugs and probes on demand

Reactions between non-biological reagents that occur readily in biological systems without being disturbed by it are called bioorthogonal. Numerous bioorthogonal reactions have been developed with a focus on reactions that link two molecules together. Although less well established, bioorthogonal reactions that dissociate and release a molecule could find widespread applications in molecular tools for biological research, the development of diagnostics, and the design of innovative therapeutics.

A key focus of the Franzini group is the development of such reactions that can release molecules inside cells or living organisms. Reactions thus discovered will then be applied to the development of tools to study cellular processes and new targeted therapeutics for cancer therapy.


Please email Dr. Raphael Franzini for inquiries or information. 


FAR Page

Research Lab

College of Pharmacy

Education History

Graduate Training EPFL
M Sc, Molecular and Biological Chemistry
Stanford University
Ph D, Organic Chemistry - Research group of Prof Eric Kool
Postdoctoral Fellowship ETH Zurich
Postdoctoral Fellow- Research group of Prof Dario Neri

Selected Publications

Journal Article

  1. "Mechanisms and Substituent Effects of Metal-Free Bioorthogonal Reactions" T. Deb, J. Tu, R. M. Franzini. Chem. Rev., 2021, in press. [Article]

  2. "Integrating DNA-encoded Chemical Libraries with Virtual Combinatorial Library Screening: Optimizing a PARP10 Inhibitor" M. Lemke, H. Ravenscroft, N. J. Rueb, D. Kireev, D. Ferraris, R. M. Franzini. Bioorg. Med. Chem. Letts., 2020, 30, 127464. [Article]

  3. "A Stable Precursor for Bioorthogonally Removable 3-Isocyanopropyloxycarbonyl (ICPrc) Protecting Groups" J. Tu, M. Xu, R. M. Franzini. Synlett, 2020, 31, 1701-1704. [Article]

    More Selected Publications