Synthesis of modified proteins via functionalization of dehydroalanine

• Published in: Current opinion in chemical biology 2018-10, Vol.46, p.71-81
• Main Authors: Dadová, Jitka, Galan, Sébastien RG, Davis, Benjamin G
• Format: Article
• Language: English
• ISSN: 1367-5931; 1879-0402
• DOI: 10.1016/j.cbpa.2018.05.022

[Display omitted] •Dha in proteins is easily and flexibly accessible under mild conditions.•Dha reactivity is used in β,γ-C–S/Se/N/C bond-formation and allows ‘zero scar’ protein mutagenesis.•Chemical mutagenesis allows functional study of PTMs in nucleosome, kinome, proteasome.•Precise, unnatural mutagenesis allows dissection of enzyme mechanism.•Direct side-chain reprogramming enables convergent synthetic protein biology. Dehydroalanine has emerged in recent years as a non-proteinogenic residue with strong chemical utility in proteins for the study of biology. In this review we cover the several methods now available for its flexible and site-selective incorporation via a variety of complementary chemical and biological techniques and examine its reactivity, allowing both creation of modified protein side-chains through a variety of bond-forming methods (C–S, C–N, C–Se, C–C) and as an activity-based probe in its own right. We illustrate its utility with selected examples of biological and technological discovery and application.