Chemical Synthesis of HMGA1a Proteins with Post-translational Modifications via Ser/Thr Ligation

被引：31

作者：

Li, Tianlu ^{[1
]}

Liu, Heng ^{[1
]}

Li, Xuechen ^{[1
]}

机构：

[1] Univ Hong Kong, State Key Lab Synthet Chem, Dept Chem, Pokfulam, Hong Kong, Peoples R China

来源：

ORGANIC LETTERS | 2016年 / 18卷 / 22期

关键词：

MEMBRANE-PROTEINS; NUCLEAR FUNCTION; CHEMISTRY; PEPTIDE; DOMAIN; DNA;

D O I：

10.1021/acs.orglett.6b03056

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The first chemical synthesis of nuclear protein HMGAla via Ser/Thr ligation is reported. Notably, Hmb (2-hydroxy-4-methoxybenzyl) exhibits crucial improvement of both the difficult coupling during solid phase peptide synthesis and the poor ligation encountered in protein synthesis. These efforts led to preparation of HMGAla analogs with well-defined phosphorylation and methylation patterns (9 synthetic proteins in total), thus overcoming the heterogeneous and 1) combinatory problems inherent to protein post-translational modifications (PTMs), and facilitating the study of the regulatory roles of such PTMs.

引用

页码：5944 / 5947

页数：4

共 32 条

[1] Pseudogene-mediated posttranscriptional silencing of HMGA1 can result in insulin resistance and type 2 diabetes [J].

Chiefari, Eusebio ;

Iiritano, Stefania ;

Paonessa, Francesco ;

Le Pera, Ilaria ;

Arcidiacono, Biagio ;

Filocamo, Mirella ;

Foti, Daniela ;

Liebhaber, Stephen A. ;

Brunetti, Antonio .

NATURE COMMUNICATIONS, 2010, 1

[2] Total chemical synthesis and electrophysiological characterization of mechanosensitive channels from Escherichia coli and Mycobacterium tuberculosis [J].

Clayton, D ;

Shapovalov, G ;

Maurer, JA ;

Dougherty, DA ;

Lester, HA ;

Kochendoerfer, GG .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (14) :4764-4769

[3]

Cleynen I, 2008, INT J ONCOL, V32, P289

[4] Lack of the architectural factor HMGA1 causes insulin resistance and diabetes in humans and mice [J].

Foti, D ;

Chiefari, E ;

Fedele, M ;

Iuliano, R ;

Brunetti, L ;

Paonessa, F ;

Manfioletti, G ;

Barbetti, F ;

Brunetti, A ;

Croce, CM ;

Fusco, A ;

Brunetti, A .

NATURE MEDICINE, 2005, 11 (07) :765-773

[5] Roles of HMGA proteins in cancer [J].

Fusco, Alfredo ;

Fedele, Monica .

NATURE REVIEWS CANCER, 2007, 7 (12) :899-910

[6] Functional relationship between high mobility group A1 (HMGA1) protein and insulin-like growth factor-binding protein 3 (IGFBP-3) in human chondrocytes [J].

Gasparini, Giorgio ;

De Gori, Marco ;

Paonessa, Francesco ;

Chiefari, Eusebio ;

Brunetti, Antonio ;

Galasso, Olimpio .

ARTHRITIS RESEARCH & THERAPY, 2012, 14 (05)

[7] Competition between HMG-I(Y), HMG-1 and histone H1 on four-way junction DNA [J].

Hill, DA ;

Reeves, R .

NUCLEIC ACIDS RESEARCH, 1997, 25 (17) :3523-3531

[8] A Helping Hand to Overcome Solubility Challenges in Chemical Protein Synthesis [J].

Jacobsen, Michael T. ;

Petersen, Mark E. ;

Ye, Xiang ;

Galibert, Mathieu ;

Lorimer, George H. ;

Aucagne, Vincent ;

Kay, Michael S. .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2016, 138 (36) :11775-11782

[9] Towards the total chemical synthesis of integral membrane proteins:: a general method for the synthesis of hydrophobic peptide-αthioester building blocks [J].

Johnson, Erik C. B. ;

Kent, Stephen B. H. .

TETRAHEDRON LETTERS, 2007, 48 (10) :1795-1799

[10] Backbone protection and its application to the synthesis of a difficult phosphopeptide sequence [J].

Johnson, T ;

Packman, LC ;

Hyde, CB ;

Owen, D ;

Quibell, M .

JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1996, (07) :719-728

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