Racemisierungsfreie Fragmentkondensation C‐terminaler Pseudoprolinpeptide an der Festphase

Heinlein, Christian; Silva, Daniel Varón; Tröster, Andrea; Schmidt, Jan Philipp; Gross, Angelina; Unverzagt, Carlo

doi:10.1002/ange.201101270

Cited by 13 publications

(9 citation statements)

References 31 publications

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“…Since N‐glycosylation requires the consensus sequence Asn‐Xaa‐Ser/Thr, we considered pseudoproline tripeptides Fmoc‐Asp(STmob)‐Xaa‐Ser/Thr(Ψ me,me pro)‐OH ( 9 ) (Figure ) as building blocks for SPPS. The C‐terminal pseudoproline not only prevents racemization of the Ser/Thr residue during fragment coupling but is also known to efficiently suppress Asi formation during SPPS . Since both the Tmob group and the pseudoproline are removed during global deprotection under acidic conditions, tripeptides of type 9 should meet all requirements for application in Fmoc‐SPPS.…”

Section: Methodsmentioning

confidence: 99%

A Tripeptide Approach to the Solid‐Phase Synthesis of Peptide Thioacids and N‐Glycopeptides

Schöwe

Keiper

Unverzagt

et al. 2019

Chemistry A European J

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A general and robust method for the incorporation of aspartates with a thioacid side chain into peptides has been developed. Pseudoproline tripeptides served as building blocks for the efficient fluorenylmethyloxycarbonyl (Fmoc) solid‐phase synthesis of thioacid‐containing peptides. These peptides were readily converted to complex N‐glycopeptides by using a fast and chemoselective one‐pot deprotection/ligation procedure. Furthermore, a novel side reaction that can lead to site‐selective peptide cleavage using thioacids (CUT) was discovered and studied in detail.

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Section: Methodsmentioning

confidence: 99%

A Tripeptide Approach to the Solid‐Phase Synthesis of Peptide Thioacids and N‐Glycopeptides

Schöwe

Keiper

Unverzagt

et al. 2019

Chemistry A European J

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“…An initial manual synthesis with standard building blocks on 2Cl‐Trt‐PS resin did not yield the 1–35 peptide due to incomplete Fmoc deprotection and difficult couplings. However, the racemization‐free solid phase segment condensation approach (Scheme a) using glycopeptide segment 14–24 with a C‐terminal pseudoproline yielded the desired SapD 1–35 thioester 5 after cleavage from the resin and in situ thioesterification . Among the resins tested 2Cl‐Trt‐ChemMatrix resin gave the highest purity and yields (24 % of 5 ).…”

Section: Methodsmentioning

confidence: 99%

“…However, the racemization‐free solid phase segment condensation approach (Scheme a) using glycopeptide segment 14–24 with a C‐terminal pseudoproline yielded the desired SapD 1–35 thioester 5 after cleavage from the resin and in situ thioesterification . Among the resins tested 2Cl‐Trt‐ChemMatrix resin gave the highest purity and yields (24 % of 5 ). Thus this resin was used for the automated assembly of the 14–35 peptide (Scheme b, resin 6 ) followed by coupling with segment 3 .…”

Section: Methodsmentioning

confidence: 99%

Synthetic Glycoforms Reveal Carbohydrate‐Dependent Bioactivity of Human Saposin D

et al. 2017

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The main glycoforms of the hydrophobic lysosomal glycoprotein saposin D( SapD) were synthesized by native chemical ligation. An approach for the challenging solid-phase synthesis of the fragments was developed. Three SapD glycoforms were obtained following ag eneral and robust refolding and purification protocol. Acrystal structure of one glycoform confirmed its native structure and disulfide pattern. Functional assays revealed that the lipid-binding properties of three SapD glycoforms are highly affected by the single sugar moiety of SapD showing ad ependency of the size and the type of Nglycan.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under http://dx.

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“…In the case of thioester B3 , polar resins were required for efficient incorporation of the oligosaccharide‐Asn building block 19 . B3 was synthesized on PEGA resin/safety catch double linker20 (18 %) and on ChemMatrix resin/2Cl‐trityl linker21 with an optimized in situ thioesterification (32 %). The glycopeptide B4 , activated as a benzimidazolone,22 was obtained in 26 % yield on a PEGA resin.…”

Section: Methodsmentioning

confidence: 99%

Semisynthesis of Biologically Active Glycoforms of the Human Cytokine Interleukin 6

Reif¹,

Siebenhaar²,

Tröster³

et al. 2014

Angewandte Chemie

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Human interleukin 6 (IL‐6) is a potent cytokine with immunomodulatory properties. As the influence of N‐glycosylation on the in vivo activities of IL‐6 could not be elucidated so far, a semisynthesis of homogeneous glycoforms of IL‐6 was established by sequential native chemical ligation. The four cysteines of IL‐6 are convenient for ligations and require only the short synthetic glycopeptide 43–48. The Cys‐peptide 49–183 could be obtained recombinantly by cleavage of a SUMO tag. The fragment 1–42 was accessible by the simultaneous cleavage of two inteins, leading to the 1–42 thioester with the native N‐terminus. Ligation and refolding studies showed that the inherently labile AspPro bond 139–140 was detrimental for the sequential C‐ to N‐terminal ligation. A reversed ligation sequence using glycopeptide hydrazides gave full‐length IL‐6 glycoproteins, which showed full bioactivity after efficient refolding and purification.

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Racemisierungsfreie Fragmentkondensation C‐terminaler Pseudoprolinpeptide an der Festphase

Cited by 13 publications

References 31 publications

A Tripeptide Approach to the Solid‐Phase Synthesis of Peptide Thioacids and N‐Glycopeptides

A Tripeptide Approach to the Solid‐Phase Synthesis of Peptide Thioacids and N‐Glycopeptides

Synthetic Glycoforms Reveal Carbohydrate‐Dependent Bioactivity of Human Saposin D

Semisynthesis of Biologically Active Glycoforms of the Human Cytokine Interleukin 6

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