Synthesis of the N-Terminal N-Myristoylated and S-Palmitoylated Undetrigintapeptide of Endothelial NO-Synthase

Machauer, Rainer; Waldmann, Herbert

doi:10.1002/(sici)1521-3773(20000417)39:8<1449::aid-anie1449>3.0.co;2-a

Cited by 17 publications

(13 citation statements)

References 5 publications

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“…Given their relative ease of synthesis, there is an abundance of examples in the literature of short, myristoylated peptides that have been produced synthetically [125–127] . For example, Waldmann and co‐workers prepared eNOS 1–26 , N‐myristoylated and S‐palmitoylated at two positions using a combination of orthogonal enzyme‐labile, acid‐labile, and noble‐metal‐labile protecting groups in a fragment condensation approach [128] . However, this approach was low yielding (<1 %) and laborious, which led the group to develop a linear solid‐phase approach that made use of the Ellman‐sulfonamide resin linker (Scheme 3 A).…”

Section: Figurementioning

confidence: 99%

“…[55,123] Waldmann and co-workers prepared eNOS 1-26 ,N -myristoylated and S-palmitoylated at two positions using ac ombination of orthogonal enzyme-labile,a cid-labile,a nd noblemetal-labile protecting groups in af ragment condensation approach. [128] However,t his approach was low yielding (< 1%)a nd laborious,w hich led the group to develop al inear solid-phase approach that made use of the Ellmansulfonamide resin linker (Scheme 3A). [113] Specifically,t he authors expanded upon their solid-phase synthesis of resinbound palmitoylated eNOS 1-16 (1;S cheme 1A), with af inal Fmoc-deprotection and on-resin myristoylation with myristoyl chloride (Myr-Cl) to assemble the full-length resin-bound precursor 28.A fter alkylation of the resin linker (with iodoacetonitrile) and subsequent cleavage,t his strategy provided the target myristoylated and dipalmitoylated eNOS 1-26 peptide 29 in am uch-improved yield of 24 %a fter purification.…”

Section: Synthesis Of Myristoylated Peptides and Proteinsmentioning

confidence: 99%

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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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Section: Figurementioning

confidence: 99%

Section: Synthesis Of Myristoylated Peptides and Proteinsmentioning

confidence: 99%

Chemical Synthesis and Semisynthesis of Lipidated Proteins

et al. 2022

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“…Several solution-phase syntheses of Ras-derived peptides were reported earlier. − However, in general, solution phase synthesis is more challenging and time-demanding than the synthesis on solid support. The growing lipidated oligopeptide becomes increasingly insoluble in the reaction medium and causes problems with the subsequent coupling steps and the purification …”

Section: Synthesis Of Lipidated Peptidesmentioning

confidence: 99%

“…The growing lipidated oligopeptide becomes increasingly insoluble in the reaction medium and causes problems with the subsequent coupling steps and the purification. 57 2.2. Solid-Phase Synthesis of Lipidated Peptides.…”

Section: Synthesis Of Lipidated Peptidesmentioning

confidence: 99%

Synthesis of Lipidated Proteins

Mejuch

Waldmann

2016

Bioconjugate Chem.

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Protein lipidation is one of the major post-translational modifications (PTM) of proteins. The attachment of the lipid moiety frequently determines the localization and the function of the lipoproteins. Lipidated proteins participate in many essential biological processes in eukaryotic cells, including vesicular trafficking, signal transduction, and regulation of the immune response. Malfunction of these cellular processes usually leads to various diseases such as cancer. Understanding the mechanism of cellular signaling and identifying the protein-protein and protein-lipid interactions in which the lipoproteins are involved is a crucial task. To achieve these goals, fully functional lipidated proteins are required. However, access to lipoproteins by means of standard expression is often rather limited. Therefore, semisynthetic methods, involving the synthesis of lipidated peptides and their subsequent chemoselective ligation to yield full-length lipoproteins, were developed. In this Review we summarize the commonly used methods for lipoprotein synthesis and the development of the corresponding chemoselective ligation techniques. Several key studies involving full-length semisynthetic lipidated Ras, Rheb, and LC3 proteins are presented.

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“…farnesyl‐ or geranylgeranyl thioethers) ruling out the use of many established protecting groups. While the introduction of enzyme‐ and noble‐metal‐sensitive protecting groups3 provided efficient solutions to this synthetic problem additional degrees of freedom are urgently required if longer peptides and peptides incorporating amino acids with reactive side‐chain functionalities like NH 2 and SH groups have to be constructed 4. This problem is particularly apparent in the case of our target compound, the maleimido‐modified H‐Ras C‐terminus 1 a (Scheme ).…”

Section: Introductionmentioning

confidence: 99%

Acid-Labile Protecting Groups for the Synthesis of Lipidated Peptides

et al. 2001

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Lipidated peptides and their neolipoprotein derivatives are efficient tools for the investigation of biological processes in molecular detail. These compounds are often acid- and base-labile, and their synthesis requires the use of a combination of blocking groups that can be removed under very mild conditions. In this article we demonstrate that the Boc urethane and different trityl-type protecting groups can be cleaved selectively under acidic conditions that are mild enough to be compatible with the demands of lipopeptide synthesis. Thus, the Boc group was cleaved with TMS triflate in the presence of lutidine, and the methyltrityl (Mtt) and the methoxytrityl (Mmt) group were removed with 1% TFA in dichloromethane in the presence of triethylsilane as cation scavenger. Removal of the phenylfluorenyl group was achieved with up to 3% TFA in dichloromethane in the presence of triethylsilane at 0 degrees C. These protecting-group techniques were successfully applied in the synthesis of differently lipidated H-Ras peptides.

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Synthesis of the N-Terminal N-Myristoylated and S-Palmitoylated Undetrigintapeptide of Endothelial NO-Synthase

Cited by 17 publications

References 5 publications

Chemical Synthesis and Semisynthesis of Lipidated Proteins

Chemical Synthesis and Semisynthesis of Lipidated Proteins

Synthesis of Lipidated Proteins

Acid-Labile Protecting Groups for the Synthesis of Lipidated Peptides

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