Bind&Bite: covalently stabilized heterodimeric coiled-coil peptides for the site-selective, cysteine-free chemical modification of proteins.

Autor:	Beutel J; Department of Chemistry and Pharmacy, University of Erlangen-Nürnberg (FAU) Erlangen Germany jutta.eichler@fau.de.; Institut Virion-Serion GmbH Würzburg Germany., Tannig P; Institute of Clinical and Molecular Virology, University of Erlangen-Nürnberg (FAU) Erlangen Germany., Di Vincenzo R; Institute of Clinical and Molecular Virology, University of Erlangen-Nürnberg (FAU) Erlangen Germany., Schumacher T; Institut Virion-Serion GmbH Würzburg Germany., Überla K; Institute of Clinical and Molecular Virology, University of Erlangen-Nürnberg (FAU) Erlangen Germany., Eichler J; Department of Chemistry and Pharmacy, University of Erlangen-Nürnberg (FAU) Erlangen Germany jutta.eichler@fau.de.
Jazyk:	angličtina
Zdroj:	RSC chemical biology [RSC Chem Biol] 2023 Aug 08; Vol. 4 (10), pp. 794-803. Date of Electronic Publication: 2023 Aug 08 (Print Publication: 2023).
DOI:	10.1039/d3cb00122a
Abstrakt:	Ensuring site-selectivity in covalent chemical modification of proteins is one of the major challenges in chemical biology and related biomedical disciplines. Most current strategies either utilize the selectivity of proteases, or are based on reactions involving the thiol groups of cysteine residues. We have modified a pair of heterodimeric coiled-coil peptides to enable the selective covalent stabilization of the dimer without using enzymes or cysteine moieties. Fusion of one peptide to the protein of interest, in combination with linking the desired chemical modification to the complementary peptide, facilitates stable, regio-selective attachment of the chemical moiety to the protein, through the formation of the covalently stabilized coiled-coil. This ligation method, which is based on the formation of isoeptide and squaramide bonds, respectively, between the coiled-coil peptides, was successfully used to selectively modify the HIV-1 envelope glycoprotein. Covalent stabilization of the coiled-coil also facilitated truncation of the peptides by one heptad sequence. Furthermore, selective addressing of individual positions of the peptides enabled the generation of mutually selective coiled-coils. The established method, termed Bind&Bite, can be expected to be beneficial for a range of biotechnological and biomedical applications, in which chemical moieties need to be stably attached to proteins in a site-selective fashion. Competing Interests: J. B. and T. S. are employees of Institut Virion-Serion GmbH. P. T., R. D. V., K. Ü. and J. E. declare no conflict of interest. (This journal is © The Royal Society of Chemistry.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu