8 Synthetic Methodology in Chemical Biology

Richard C. Brewster and Stephen Wallace

Institute of Quantitative Biology, Biochemistry and Biotechnology, School of Biological Sciences, University of Edinburgh, Edinburgh, UK

8.1 Introduction

Chemical biology is a diverse field encompassing a wide range of techniques and processes. One challenging area in this field is the study of biomolecules in their native environments to determine structure, function and dynamics.

This chapter looks to introduce some of the different approaches to biomolecule modification in this field. The first section will look at in vitro methods, starting with an introduction to peptide synthesis and how these peptides can be ligated to produce synthetic proteins. We will then consider some of the different chemical reactions for modifying endogenous amino acids on proteins in vitro.

The second section will discuss the use of bioorthogonal reactions for protein modification in vivo. We will look at how design principles can be used to improve reaction kinetics in vivo and how the judicious choice of a reaction manifold can lead to improved properties in single cells and whole animals. We will then provide an overview of different methods for the introduction of new functional groups into living cells using both metabolic and synthetic biology approaches.

Finally, a case study will consider the field of histone post‐translational modifications (PTMs). Three very different methods for incorporating ...

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