title: Site-selective protein-modification chemistry for basic biology and drug development.
abstract: Nature has produced intricate machinery to covalently diversify the structure of proteins after their synthesis in the ribosome. In an attempt to mimic nature, chemists have developed a large set of reactions that enable post-expression modification of proteins at pre-determined sites. These reactions are now used to selectively install particular modifications on proteins for many biological and therapeutic applications. For example, they provide an opportunity to install post-translational modifications on proteins to determine their exact biological roles. Labelling of proteins in live cells with fluorescent dyes allows protein uptake and intracellular trafficking to be tracked and also enables physiological parameters to be measured optically. Through the conjugation of potent cytotoxicants to antibodies, novel anti-cancer drugs with improved efficacy and reduced side effects may be obtained. In this Perspective, we highlight the most exciting current and future applications of chemical site-selective protein modification and consider which hurdles still need to be overcome for more widespread use.
authors.affiliation: Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology Zürich (ETH Zürich), Vladimir Prelog Weg 1-5/10, CH-8093 Zürich, Switzerland.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Krall
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal.
authors.forename: Filipa P
authors.initials: FP
authors.lastname: da Cruz
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.
authors.forename: Omar
authors.initials: O
authors.lastname: Boutureira
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal.|Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.
authors.forename: Gonçalo J L
authors.initials: GJ
authors.lastname: Bernardes
mesh_terms: D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D011506:Proteins / Q000737:chemistry*
chemical_list: D011506:Proteins