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Postligation-Desulfurization: A General Approach for Chemical Protein Synthesis

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Protein Ligation and Total Synthesis II

Part of the book series: Topics in Current Chemistry ((TOPCURRCHEM,volume 363))

Abstract

Native chemical ligation, involving regioselective and chemoselective coupling of two unprotected peptide segments, enabled the synthesis of polypeptide with more than 200 amino acids. However, cysteine was indispensable in this synthetic technique in its initial format, which limited its further application. Thus, considerable effort has been put into breaking the restriction of cysteine-containing ligation. As a consequence, postligation-desulfurization, concerning thiol-mediated ligation followed by desulfurization, was developed. This review describes the development and recent progress on the chemical synthesis of peptides and proteins encompassing postligation-desulfurization at alanine, valine, lysine, threonine, leucine, proline, arginine, aspartic acid, glutamate, phenylalanine, glutamine, and tryptophan.

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Abbreviations

Ac:

Acetyl

AFGP:

Antifreeze glycoprotein

Ala:

Alanine

Alloc:

Allyloxycarbonyl

Arg:

Arginine

Asp:

Aspartic acid

Boc:

tert-Butyloxycarbonyl

CXCR:

Chemokine receptor

Cys:

Cysteine

DBU:

1,8-Diazabicyclo[5.4.0]undec-7-ene

DIAD:

Diisopropyl azodicarboxylate

DIBAL-H:

Diisobutylaluminum hydride

DIPEA:

Ethyldiisopropylamine

DMAP:

4-Dimethylaminopyridine

DMF:

N,N-Dimethylformamide

DMSO:

Dimethyl sulfoxide

EDC:

N-(3-Dimethylanino propyl)-N′-ethylcarbodiimide

Fmoc:

Fluorenylmethyloxycarbonyl

Gln:

Glutamine

Glu:

Glutamic acid

Gn:

Guanidine

HEPES:

2-[4-(2-Hydroxyethyl)-1-peperazinyl]ethanesulfonic acid

HMDS:

Bis(trimethylsilyl)amide

HOOBt:

Hydroxy-3,4-dihydro-4-oxo-1,2,3-benzotriazine

hPTHrP:

Human parathyroid hormone-related protein

KHMDS:

Potassium 1,1,1,3,3,3-hexamethyldisilazane

LC-MS:

Liquid chromatography-mass spectrometry

Leu:

Leucine

Lys:

Lysine

mCPBA:

meta-Chloroperoxybenzoic acid

MESNa:

Sodium-2-mercaptoethane sulfonate

Met:

Methionine

MMTS:

(S)-Methyl methanethiosulfonate

MPAA:

Mercaptophenylacetic acid

Ms:

Methanesulfonyl

NCL:

Native chemical ligation

NMM:

N-Methylmorpholine

NVOC:

o-Nitroveratryloxycarbonyl

Pen:

Penicillamine

Phe:

Phenylalanine

PhFl:

9-Phenylfluroenyl

Pro:

Proline

PyBOP:

Benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate

rt:

Room temperature

Ser:

Serine

SPPS:

Solid phase peptide synthesis

tBu:

tert-Butyl

TBAF:

Tetra-n-butylammonium fluoride

TBS:

tert-Butyldimethylsilyl

TCEP:

Tris(2-carboxyethyl)phosphine

TFA:

Trifluoroacetic acid

TFE:

Trifluoroethanol

TFET:

Trifluoroethanethiol

THF:

Tetrahydrofuran

Thr:

Threonine

TIS:

Triisopropylsilane

TMSE:

Trimethylsilylethyl

Tris:

Tri(hydroxymethyl)aminomethane

Trp:

Tryptophan

Trt:

Trityl

Ts:

4-Toluenesulfonyl

Ub:

Ubiquitin

UV:

Ultraviolet

VA-044:

2,2′-Azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride

Val:

Valine

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Acknowledgments

We are grateful for financial support by the National Natural Science Foundation of China (21272082, 21402055, 21402056, 21472054), the Specialized Research Fund for the Doctoral Program of Higher Education (20120142120092), the Recruitment Program of Global Youth Experts of China, the State Key Laboratory of Bio-organic and Natural Products Chemistry (SKLBNPC13425), and Huazhong University of Science and Technology (2014ZZGH015), the Fundamental Research Funds for the Central Universities (Project 2014QC007).

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Authors and Affiliations

  1. Department of Chemistry, College of Science, Huazhong Agricultural University, Wuhan, 430070, China

    Jimei Ma

  2. School of Pharmacy, Huazhong University of Science and Technology, Wuhan, 430030, China

    Jing Zeng & Qian Wan

  3. Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China

    Qian Wan

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  1. Jimei Ma
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  2. Jing Zeng
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Correspondence to Qian Wan .

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Editors and Affiliations

  1. Department of Chemistry, Tsinghua University, Beijing, China

    Lei Liu

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Ma, J., Zeng, J., Wan, Q. (2014). Postligation-Desulfurization: A General Approach for Chemical Protein Synthesis. In: Liu, L. (eds) Protein Ligation and Total Synthesis II. Topics in Current Chemistry, vol 363. Springer, Cham. https://doi.org/10.1007/128_2014_594

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