朝着同型促红细胞生成素迈进：通过“丙氨酸”连接化学合成 Ala1-Gly28 糖肽结构域。
Toward homogeneous erythropoietin: chemical synthesis of the Ala1-Gly28 glycopeptide domain by "alanine" ligation.
机构信息
Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, New York 10065, USA.
出版信息
J Am Chem Soc. 2009 Apr 22;131(15):5438-43. doi: 10.1021/ja808707w.
Abstract
The Ala(1)-Gly(28) glycopeptide fragment (28) of EPO was prepared by chemical synthesis as a single glycoform. Key steps in the synthesis include attachment of a complex dodecasaccharide (7) to a seven amino acid peptide via Lansbury aspartylation, native chemical ligation to join peptide 19 with the glycopeptide domain 18, and a selective desulfurization at the ligation site to reveal the natural Ala(19). This glycopeptide fragment (28) contains both the requisite N-linked dodecasaccharide and a C-terminal (alpha)thioester handle, the latter feature permitting direct coupling with a glycopeptide fragment bearing N-terminal Cys(29) without further functionalization.
摘要
EPO 的 Ala(1)-Gly(28)糖肽片段（28）通过化学合成制备为单一糖型。合成中的关键步骤包括通过 Lansbury 天冬氨酸酰化将复杂的十二聚糖（7）连接到七肽上，通过天然化学连接将肽 19 与糖肽结构域 18 连接，以及在连接点选择性脱硫以揭示天然 Ala(19)。该糖肽片段（28）既含有必需的 N-连接十二聚糖，又含有 C 末端（α）硫酯柄，后者的特征是可以直接与带有 N 末端 Cys(29)的糖肽片段偶联，而无需进一步功能化。
相似文献
1
Toward homogeneous erythropoietin: chemical synthesis of the Ala1-Gly28 glycopeptide domain by "alanine" ligation.
J Am Chem Soc. 2009 Apr 22;131(15):5438-43. doi: 10.1021/ja808707w.
2
Toward homogeneous erythropoietin: fine tuning of the C-terminal acyl donor in the chemical synthesis of the Cys29-Gly77 glycopeptide domain.
J Am Chem Soc. 2009 Apr 22;131(15):5432-7. doi: 10.1021/ja808705v.
3
Toward homogeneous erythropoietin: non-NCL-based chemical synthesis of the Gln78-Arg166 glycopeptide domain.
J Am Chem Soc. 2009 Apr 22;131(15):5424-31. doi: 10.1021/ja808704m.
4
Chemical synthesis of erythropoietin glycoforms for insights into the relationship between glycosylation pattern and bioactivity.
Sci Adv. 2016 Jan 15;2(1):e1500678. doi: 10.1126/sciadv.1500678. eCollection 2016 Jan.
5
Probing the stability of nonglycosylated wild-type erythropoietin protein via reiterative alanine ligations.
Proc Natl Acad Sci U S A. 2012 May 8;109(19):7196-201. doi: 10.1073/pnas.1202762109. Epub 2012 Apr 12.
6
Total synthesis of erythropoietin through the development and exploitation of enabling synthetic technologies.
Angew Chem Int Ed Engl. 2013 Jan 7;52(2):505-7. doi: 10.1002/anie.201207906. Epub 2012 Nov 23.
7
Chemoenzymatic Synthesis of HIV-1 Glycopeptide Antigens.
Methods Mol Biol. 2020;2103:249-262. doi: 10.1007/978-1-0716-0227-0_17.
8
Chemical and Enzymatic Synthesis of Sialylated Glycoforms of Human Erythropoietin.
Angew Chem Int Ed Engl. 2021 Dec 1;60(49):25922-25932. doi: 10.1002/anie.202110013. Epub 2021 Nov 2.
9
Uncovering a latent ligation site for glycopeptide synthesis.
Angew Chem Int Ed Engl. 2008;47(29):5402-6. doi: 10.1002/anie.200801097.
10
Convenient synthesis of a sialylglycopeptide-thioester having an intact and homogeneous complex-type disialyl-oligosaccharide.
Carbohydr Res. 2006 Jul 24;341(10):1333-40. doi: 10.1016/j.carres.2006.04.037. Epub 2006 May 15.
引用本文的文献
1
Advances in the chemical synthesis of human proteoforms.
Sci China Life Sci. 2025 Apr 8. doi: 10.1007/s11427-024-2860-5.
2
The C-Terminal O-S Acyl Shift Pathway under Acidic Condition to Propose Peptide-Thioesters.
Molecules. 2016 Nov 17;21(11):1559. doi: 10.3390/molecules21111559.
3
The winding pathway to erythropoietin along the chemistry-biology frontier: a success at last.
Angew Chem Int Ed Engl. 2013 Jul 22;52(30):7646-65. doi: 10.1002/anie.201301666. Epub 2013 Jun 17.
4
Toward Homogeneous Erythropoietin: Application of Metal Free Dethiylation in the Chemical Synthesis of the Ala79-Arg166 Glycopeptide Domain.
Isr J Chem. 2011 Nov;51(8-9):968-976. doi: 10.1002/ijch.201100077.
5
Synthetic glycopeptides and glycoproteins with applications in biological research.
Beilstein J Org Chem. 2012;8:804-18. doi: 10.3762/bjoc.8.90. Epub 2012 May 30.
6
At last: erythropoietin as a single glycoform.
Angew Chem Int Ed Engl. 2012 Nov 12;51(46):11576-84. doi: 10.1002/anie.201206090. Epub 2012 Sep 25.
7
An advance in the chemical synthesis of homogeneous N-linked glycopolypeptides by convergent aspartylation.
Angew Chem Int Ed Engl. 2012 Nov 12;51(46):11571-5. doi: 10.1002/anie.201205038. Epub 2012 Sep 25.
8
Engineering of therapeutic polypeptides through chemical synthesis: early lessons from human parathyroid hormone and analogues.
J Am Chem Soc. 2012 Sep 12;134(36):15122-9. doi: 10.1021/ja306637u. Epub 2012 Aug 29.
9
Probing the stability of nonglycosylated wild-type erythropoietin protein via reiterative alanine ligations.
Proc Natl Acad Sci U S A. 2012 May 8;109(19):7196-201. doi: 10.1073/pnas.1202762109. Epub 2012 Apr 12.
10
Advances in proline ligation.
J Am Chem Soc. 2012 Feb 29;134(8):3912-6. doi: 10.1021/ja212182q. Epub 2012 Feb 15.
本文引用的文献
1
Toward homogeneous erythropoietin: fine tuning of the C-terminal acyl donor in the chemical synthesis of the Cys29-Gly77 glycopeptide domain.
J Am Chem Soc. 2009 Apr 22;131(15):5432-7. doi: 10.1021/ja808705v.
2
Toward homogeneous erythropoietin: non-NCL-based chemical synthesis of the Gln78-Arg166 glycopeptide domain.
J Am Chem Soc. 2009 Apr 22;131(15):5424-31. doi: 10.1021/ja808704m.
3
Oxo-ester mediated native chemical ligation: concept and applications.
J Am Chem Soc. 2008 Nov 26;130(47):15814-6. doi: 10.1021/ja804993y.
4
Native chemical ligation at valine: a contribution to peptide and glycopeptide synthesis.
Angew Chem Int Ed Engl. 2008;47(44):8521-4. doi: 10.1002/anie.200803523.
5
Native chemical ligation at valine.
Angew Chem Int Ed Engl. 2008;47(36):6807-10. doi: 10.1002/anie.200801590.
6
Uncovering a latent ligation site for glycopeptide synthesis.
Angew Chem Int Ed Engl. 2008;47(29):5402-6. doi: 10.1002/anie.200801097.
7
Cysteine-free peptide and glycopeptide ligation by direct aminolysis.
Angew Chem Int Ed Engl. 2008;47(23):4411-5. doi: 10.1002/anie.200705298.
8
New chemistry with old functional groups: on the reaction of isonitriles with carboxylic acids--a route to various amide types.
J Am Chem Soc. 2008 Apr 23;130(16):5446-8. doi: 10.1021/ja800612r. Epub 2008 Mar 28.
9
Chemical synthesis of a glycoprotein having an intact human complex-type sialyloligosaccharide under the Boc and Fmoc synthetic strategies.
J Am Chem Soc. 2008 Jan 16;130(2):501-10. doi: 10.1021/ja072543f. Epub 2007 Dec 18.
10
Free-radical-based, specific desulfurization of cysteine: a powerful advance in the synthesis of polypeptides and glycopolypeptides.
Angew Chem Int Ed Engl. 2007;46(48):9248-52. doi: 10.1002/anie.200704195.
Zotero 插件