Organic chemistry allows for the modification and chemical preparation of protein analogues for various studies. The thiolate side chain of the Cys residue has been a key functionality in these ventures. In order to generate complex molecular targets, there is a particular need to incorporate orthogonal protecting groups of the thiolated amino acids to control the directionality of synthesis and modification site. Here, we demonstrate the tuning of palladium chemoselectivity in aqueous medium for on-demand deprotection of several Cys-protecting groups that are useful in protein synthesis and modification. These tools allow the preparation of highly complex analogues as we demonstrate in the synthesis of the copper storage protein and selectively modified peptides with multiple Cys residues. We also report the synthesis of an activity-based probe comprising ubiquitinated histone H2A and its incorporation into nucleosomes and demonstrate its reactivity with deubiquitinating enzyme to generate a covalent nucleosome–enzyme complex.
|State||Published - 1 Dec 2018|
Bibliographical noteFunding Information:
This study was partially supported by the United States-Israel Binational Science Foundation, BSF 2014029 (A.B. and C.W.). A.B. holds The Jordan and Irene Tark Academic Chair. M. J. thanks the Israel Council of Higher Education for a fellowship under the outstanding doctoral student’s program and BSF for a Rahamimoff travel grant.
© 2018, The Author(s).