Synthesis at the Interface of Chemistry and Biology

Abstract

As the focus of synthesis increasingly shifts from its historical emphasis on molecular structure to function, improved strategies are required to efficiently generate small and large molecules, and even systems of molecules, with defined physical, chemical and biological properties. Given the remarkable array of functions carried out by the molecules found in living organisms, Mother Nature offers both inspiration and help in this regard through an approach to synthesis that seamlessly interfaces biology and chemistry. Here we illustrate the potential of this approach and overview some opportunities and challenges in the coming years.

A small molecule accelerates neuronal differentiation in the adult rat

“…A very recent study describes the identification of a proneurogenic small molecule that protects newborn hippocampal neurons from apoptosis (31). Moreover, a series of experimental small molecules that control the self-renewal and differentiation of stem and progenitor cells in vitro have been described (3,9,(32)(33)(34)(35)(36).…”

Probing Protein–Protein Interactions with a Genetically Encoded Photo‐crosslinking Amino Acid

“…Alternatively, photo-crosslinking moieties can be site-specifically introduced into proteins chemically or enzymatically, [12] or in response to nonsense codons by means of orthogonal amber suppressor tRNA/aminoacyl-tRNA synthetase pairs. [13] For example, amino acids containing benzophenone, diazirine, and aryl azide side chains have all been genetically encoded in prokaryotic and eukaryotic organisms, [14][15][16][17][18] and used to crosslink protein-protein and protein-DNA interactions in vitro and in living cells. [19][20][21][22][23] However, the size and photochemical reactivity of these photo-crosslinkers might not be ideal for a given site in a target protein of interest.…”

Comparing the Enantioselective Power of Steric and Electrostatic Effects in Transition‐Metal‐Catalyzed Asymmetric Synthesis

“…[37] This interchange between these effects is striking, and indicates possible directions for the development of better performing catalytic systems as the focus of chemistry is shifting from molecular structure to molecular function. [38] It is probably a weakness of our classification schemes that have induced to privilege more the easy to understand and quantify steric handle relative to the more complex electrostatic counterpart.…”