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Chemical Biology

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Chemical Biology

Coordinator
Rita Ventura

Other lecturers
Birgit Wiltschi, Rita Ventura and Ana Cecília Afonso Roque

Objectives
The objective of this CU is to expose the students to a significantly broad, yet not exhaustive view of one of the

methodological areas that has spurred many of the recent forward leaps of Biology, both in the ability to interrogate it and to manipulate its function. At the end of this CU students should have recognized and assimilated the new possibilities that emerge when biological problems are tackled by the articulate use of knowledge arising from different areas like synthetic and natural product chemistry, pharmacology, biochemistry and structural biochemistry. In this context, teaching is centered on some of the essential tools of Chemical Biology (CB) and its objective is to form a way of thinking and researching Biology, which is crucial to consolidate at the entry of a PhD program.
From the vast area of real and conceptual aspects of CB this CU will focus on topics judged to have higher immediate impact and broader formative profile.  

Syllabus

1. Molecular recognition and binding

Analyzing molecular recognition and binding;

2. Drug design, discovery and resistance

Optimization of lead-target interactions

3. Self-assembling bio-inspired systems

Supramolecular interactions involved in peptide/protein self-assembly

Protein in vitro evolution for recognition or function (Catalysis)

Minimal and artificial versions of enzymes. Functional assays.

4. Chemical methods to synthesize DNA, RNA for diagnostics and therapeutics.

Synthesis of oligonucleotides and incorporation of non-natural nucleotides;

siRNA and rybozymes.

5. Chemical methods to synthesize proteins and peptides

Incorporation of non-natural amino acids.

Design and Applications of “de novo” proteins

6. Bioconjugates and for in vivo and. Protein-drug conjugates

Biocompatible click reactions and bioorthogonal reactions.

7. Labelling Strategies for Cell Biology

8. Artificial Nanoparticles, their synthesis and functionalisation

Evaluation
The evaluation of each student will be based on both the quality and intensity of his/her participation in such discussions.

Main Bibliography

  • Essentials of Glycobiology, Third Edition 3rd Edition by Ajit Varki (Editor), Richard D. Cummings (Editor), Jeffrey D. Esko (Editor), Pamela Stanley (Editor), Gerald Hart (Editor), Markus Aebi (Editor), Alan G. Darvill (Editor), Taroh Kinoshita (Editor), Nicolle H. Packer (Editor), Cold Spring Harbor Laboratory Press (2017)

  • Chemical Biology: From Small Molecules to Systems Biology and Drug Design, 1–3, Eds. S.L. Schreiber, T.M. Kapoor and G. Wess, Wiley VCH (2007) .

  • Miller, A. & Tanner, J. Essentials of Chemical Biology-Structure and Dynamics of Biological Macromolecules. Wiley VCH (2008).

  • Waldmann, H. & Janning, P. Petra Chemical Biology: Learning through case studies. Wiley VCH (2009).

  • Roque, A. C. A. Ed. Ligand Macromolecular Interactions in Drug Discovery. Humana Press (2010).

  • Targeting Protein-Protein Interaction by Small Molecules, Lingyan Jin, Weiru Wang, Guowei Fang

  • Annual Review of Pharmacology and Toxicology 2014 54:1, 435-456.

  • Liu CC, Schultz PG: Adding new chemistries to the genetic code. Annu Rev Biochem 2010, 79:413-444.

  • Sletten, E. M. and Bertozzi, C. R.: From Mechanism to Mouse: A Tale of Two Bioorthogonal Reactions Acc.s of Chem. Res. 2011, 44, 666–676.

  • Systems Biology and Systems Chemistry: New Directions for Drug Discovery Brown, J. B.; Okuno, Y. Chemistry & Biology 2012, 19 (1), 23–28.

  • Zhang, Y.; Park, K.; Suazo, K. F.; Distefano, M. D. Recent progress in enzymatic protein labelling techniques and their applications, Chem. Soc. Rev., 2018, 47, 9106.

  • Rodriguez-Rivera, F. P.; Zhou, X.; Julie A. Theriot, J. A.; Bertozzi, C. A. Visualization of mycobacterial membrane dynamics in live cells, J. Am. Chem. Soc. 2017, 139, 3488.

 

 

 

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