Examining Several Strategies for the Chemical Synthesis of Phosphorylated Histone H3 Reveals the Effectiveness of the Convergent Approach

Muhammad Jbara; Suman Kumar Maity; Ashraf Brik

doi:10.1002/ejoc.201900257

Examining Several Strategies for the Chemical Synthesis of Phosphorylated Histone H3 Reveals the Effectiveness of the Convergent Approach

Muhammad Jbara, Suman Kumar Maity, Ashraf Brik

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	3128-3132
Number of pages	5
Journal	European Journal of Organic Chemistry
Volume	2020
Issue number	21
DOIs	https://doi.org/10.1002/ejoc.201900257
State	Published - 8 Jun 2020
Externally published	Yes

Keywords

Chemical protein synthesis
Convergent synthesis
Histone 3
Palladium
Phosphorylation

ASJC Scopus subject areas

Physical and Theoretical Chemistry
Organic Chemistry

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10.1002/ejoc.201900257

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title = "Examining Several Strategies for the Chemical Synthesis of Phosphorylated Histone H3 Reveals the Effectiveness of the Convergent Approach",

abstract = "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.",

keywords = "Chemical protein synthesis, Convergent synthesis, Histone 3, Palladium, Phosphorylation",

author = "Muhammad Jbara and Maity, {Suman Kumar} and Ashraf Brik",

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year = "2020",

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AU - Jbara, Muhammad

AU - Maity, Suman Kumar

AU - Brik, Ashraf

PY - 2020/6/8

Y1 - 2020/6/8

N2 - 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.

AB - 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.

KW - Chemical protein synthesis

KW - Convergent synthesis

KW - Histone 3

KW - Palladium

KW - Phosphorylation

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DO - 10.1002/ejoc.201900257

M3 - Article

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SN - 1434-193X

VL - 2020

SP - 3128

EP - 3132

JO - European Journal of Organic Chemistry

JF - European Journal of Organic Chemistry

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Examining Several Strategies for the Chemical Synthesis of Phosphorylated Histone H3 Reveals the Effectiveness of the Convergent Approach

Abstract

Keywords

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