Chemical Synthesis and Biological Function of Lipidated Proteins

Yang, Aimin; Zhao, Lei

doi:10.1007/128_2014_582

Cited by 13 publications

(7 citation statements)

References 116 publications

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“…MTG is easily accessible and displays sufficient reactivity.O ur streamlined synthesis of ubiquitin (85 %i solated yield, 30 mg scale) demonstrates that this strategy has the potential toe fficiently generate large-scale high-quality proteins.R acemic Xray crystallography was employed to characterize the synthetic ubiquitin. We hope that the utility of this one-pot NCL-MFD approachc an be demonstrated in the chemical synthesis of post-translational modifiedp roteins [30,36] (e.g.,glycosylatedproteins, [37] lipidated proteins, [38] ubiquitinated proteins, [39] and histone derivatives) [40] in future studies.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of l‐ and d‐Ubiquitin by One‐Pot Ligation and Metal‐Free Desulfurization

Huang

Chen

Gao

et al. 2016

Chemistry A European J

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Native chemical ligation combined with desulfurization has become a powerful strategy for the chemical synthesis of proteins. Here we describe the use of a new thiol additive, methyl thioglycolate, to accomplish one-pot native chemical ligation and metal-free desulfurization for chemical protein synthesis. This one-pot strategy was used to prepare ubiquitin from two or three peptide segments. Circular dichroism spectroscopy and racemic protein X-ray crystallography confirmed the correct folding of ubiquitin. Our results demonstrate that proteins synthesized chemically by streamlined 9-fluorenylmethoxycarbonyl (Fmoc) solid-phase peptide synthesis coupled with a one-pot ligation-desulfurization strategy can supply useful molecules with sufficient purity for crystallographic studies.

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Section: Resultsmentioning

confidence: 99%

Synthesis of l‐ and d‐Ubiquitin by One‐Pot Ligation and Metal‐Free Desulfurization

Huang

Chen

Gao

et al. 2016

Chemistry A European J

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“…Ther esulting carboxylate group of the side-chain-prenylated Cys residue is subsequently methylated by the enzyme isoprenylcysteine carboxymethyltransferase enzyme,R ab (Ras-related in brain) geranylgeranyl transferase (GGTase-II or Rab-GGTase) employs GGpp as as ubstrate to specifically transfer either one or two geranylgeranyl groups.T he C-terminal prenylation motifs that are found within the family of Rab proteins are mostly CC and CXC but also include CCX, CCXX, and CXX. [9,19] Af ourth type of protein prenyltransferase called GGTase3 has very recently been discovered and is responsible for geranylgeranylating the ubiquitin ligase FBXL2, thereby linking it to the membrane and allowing polyubiquitylation of membraneanchored proteins. [20] It similarly modifies SNARE proteins, such as Ykt6, which is ap rerequisite for proper assembly of the Golgi SNARE complex.…”

Section: Prenylationmentioning

confidence: 99%

Chemical Synthesis and Semisynthesis of Lipidated Proteins

et al. 2022

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Lipidation is a ubiquitous modification of peptides and proteins that can occur either co‐ or post‐translationally. An array of different lipid classes can adorn proteins and has been shown to influence a number of crucial biological activities, including the regulation of signaling, cell–cell adhesion events, and the anchoring of proteins to lipid rafts and phospholipid membranes. Whereas nature employs a range of enzymes to install lipid modifications onto proteins, the use of these for the chemoenzymatic generation of lipidated proteins is often inefficient or impractical. An alternative is to harness the power of modern synthetic and semisynthetic technologies to access lipid‐modified proteins in a pure and homogeneously modified form. This Review aims to highlight significant advances in the development of lipidation and ligation chemistry and their implementation in the synthesis and semisynthesis of homogeneous lipidated proteins that have enabled the influence of these modifications on protein structure and function to be uncovered.

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“…Die C-terminalen Prenylierungsmotive,d ie in der Familie der Rab-Proteine gefunden wurden, sind meistens CC und CXC,a ber auch CCX, CCXX und CXX. [9,19] Eine vierte Art einer Prenyltransferase mit dem Namen GGTase3 wurde erst vor kurzem entdeckt und ist fürdie Geranylgeranylierung der Ubiquitin-Ligase FBXL2 verantwortlich, wodurch diese sich an die Membran anlagert und die Polyubiquitylierung von membranverankerten Proteinen ermçglicht. [20] In ähnlicher Weise modifiziert es SNARE-Proteine wie Ykt6, was eine Voraussetzung fürd en korrekten Aufbau des Golgi-SNARE-Komplexes ist.…”

Section: Prenylierungunclassified

Chemische Synthese und Semisynthese von lipidierten Proteinen

Hanna¹,

Kriegesmann

Dowman

et al. 2022

Angewandte Chemie

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Lipidierung ist eine ubiquitäre Modifikation von Peptiden und Proteinen, die entweder co‐ oder posttranslational auftreten kann. Für die Vielzahl von Lipidklassen wurde gezeigt, dass diese viele entscheidende biologische Aktivitäten, z. B. die Regulierung der Signalweiterleitung, Zell‐Zell‐Adhäsion sowie die Anlagerung von Proteinen an Lipid‐Rafts und Phospholipidmembranen, beeinflussen. Während die Natur Enzyme nutzt, um Lipidmodifikationen in Proteine einzubringen, ist ihre Nutzung für die chemoenzymatische Herstellung von lipidierten Proteinen häufig ineffizient. Eine Alternative ist die Kombination moderner synthetischer und semisynthetischer Techniken, um lipidierte Proteine in reiner und homogen modifizierter Form zu erhalten. Dieser Aufsatz erörtert Fortschritte in der Entwicklung der Lipidierungs‐ und Ligationschemie und deren Anwendung in der Synthese und Semisynthese homogen lipidierter Proteine, die es ermöglichen, den Einfluss dieser Modifikationen auf die Proteinstruktur und ‐funktion zu untersuchen.

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Chemical Synthesis and Biological Function of Lipidated Proteins

Cited by 13 publications

References 116 publications

Synthesis of l‐ and d‐Ubiquitin by One‐Pot Ligation and Metal‐Free Desulfurization

Synthesis of l‐ and d‐Ubiquitin by One‐Pot Ligation and Metal‐Free Desulfurization

Chemical Synthesis and Semisynthesis of Lipidated Proteins

Chemische Synthese und Semisynthese von lipidierten Proteinen

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