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Examining Several Strategies for the Chemical Synthesis of Phosphorylated Histone H3 Reveals the Effectiveness of the Convergent Approach
Author(s) -
Jbara Muhammad,
Maity Suman Kumar,
Brik Ashraf
Publication year - 2020
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201900257
Subject(s) - histone h3 , chemistry , phosphorylation , histone , acetylation , native chemical ligation , thiazolidine , convergent synthesis , biochemistry , microbiology and biotechnology , dna , chemical synthesis , stereochemistry , biology , in vitro , gene
Phosphorylation of Ser57 of the histone H3 was suggested to interact with the acetylated Lys56 of histone H3 and possibly affect DNA replication. Yet the exact role of Ser57 remains unknown due to difficulties in obtaining phosphorylated H3 at Ser57. Herein, we present the challenges and the solutions in the first total chemical synthesis of phosphorylated and unphosphorylated histone H3 analogues utilizing hydrazide‐based native chemical ligation approach coupled with palladium‐mediated thiazolidine decaging chemistry to provide each one of these analogues in highly efficient manner. We envision this synthesis would set the ground to elucidating the role of the phosphorylation and its cross‐talk with acetylation mark in H3 in the DNA damage response.