Convergent Solid‐Phase Synthesis of N‐Glycopeptides Facilitated by Pseudoprolines at Consensus‐Sequence Ser/Thr Residues

Ullmann, Vera; Rädisch, Marisa; Boos, Irene; Freund, Jutta; Pöhner, Claudia; Schwarzinger, Stefan; Unverzagt, Carlo

doi:10.1002/ange.201204272

Cited by 36 publications

(29 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…6). The SPPS synthesis provided polypeptide 11; installation of a temporary pseudoproline group at the Glu 38 -Thr 39 position (see underline) served to effectively suppress undesired aspartimide formation at the allyl-protected Asp 37 residue (30,31). Selective Pd(0)-catalyzed deallylation, followed by Lansbury aspartylation (32, 33) with chitobiose, afforded glycopeptide 12.…”

Section: Synthesis Of Glycosylated Gm-csf Analogsmentioning

confidence: 99%

Synthesis of granulocyte–macrophage colony-stimulating factor as homogeneous glycoforms and early comparisons with yeast cell-derived material

Zhang

Johnston

Shieh

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Significance As biologically active glycoproteins are increasingly investigated as potential therapeutic agents, there is a growing demand for the development of strategies for the synthesis of homogeneous, single-glycoform constructs for the purposes of rigorous evaluation. Currently, most glycoproteins are accessed through recombinant methods as complex mixtures of glycoforms. Granulocyte–macrophage colony-stimulating factor (GM-CSF) is an important glycoprotein therapeutic, used to stimulate the immune system following bone-marrow transplant and chemotherapy. GM-CSF is also being explored as a potential immunoadjuvant for anticancer vaccines. We have completed a chemical synthesis of homogeneous, single-glycoform GM-CSF. Through adaptation of this modular synthetic route, it will be possible to gain access to a menu of single-glycoform GM-CSF congeners for a wide range of biological studies.

show abstract

Section: Synthesis Of Glycosylated Gm-csf Analogsmentioning

confidence: 99%

Synthesis of granulocyte–macrophage colony-stimulating factor as homogeneous glycoforms and early comparisons with yeast cell-derived material

Zhang

Johnston

Shieh

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Under the same SPPS protocols, fragment F2 (Cys23-Tyr65, 3) was isolated in only 9% yield due to a high level of aspartimide formation. Application of the Asp (OMpe) derivative (Fmoc-(O-3-methyl-pent-3-yl)aspartic acid, commercially available) (36) and a strategically placed pseudoproline dipeptide at Ile57-Ser58 increased the isolated yield following RP-HPLC to 35% (37,38). Following subjection of peptide fragments 2 and 3 to kinetic ligation buffer [6 M guanidinium hydrochloride (Gnd), 200 mM phosphate buffer, 20 mM tris(2-carboxyethyl)phosphine (TCEP), pH 7.2] (34), formation of the ligated product 4 was confirmed by liquid chromatography-mass spectrometry (LC-MS) (Fig.…”

Section: Resultsmentioning

confidence: 99%

Chemical synthesis of the ATAD2 bromodomain

Creech

Paresi

2014

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Due to the emerging importance of the bromodomain binding region in the study of epigenetic effectors and the vast implications for a wide variety of human disease, the bromodomain region of human ATPase family AAA+ (ATPases associated with diverse cellular activities) domain-containing protein 2 (ATAD2) was targeted for chemical synthesis. The ATAD2 bromodomain (130 aa) was divided into five strategic fragments to be assembled using native chemical ligation with a focus on maximal convergency and efficiency. The fragments were assembled with one cysteine and three thioleucine ligations, unveiling the native alanine and leucine amino acids at the ligation points following metal-free dethiylation. Synthetic highlights of the study are a photolabile dimethoxynitrobenzyl-protected glutamic acid side chain used to impede hydrolysis of the C-terminal Glu-thioester, a thiazolidine-protected thioleucine, and an efficient assembly of three fragments in a single reaction vessel with dual-mode kineticstandard chemical ligation. With a focus on material throughput and convergency, the five peptide fragments were assembled into the native ATAD2 bromodomain region with a total of three HPLC events in 8% overall yield from the fragments.solid-phase peptide synthesis | desulfurization | peptide retrosynthesis

show abstract

“…Die Kupplung von (4) an die Peptide (5) und (7) erfolgte nach einer modifizierten Lansbury‐Aspartylierung. Hierbei verhinderte ein — anstelle des in der Konsensussequenz enthaltenen Thr‐162 — eingeführtes Pseudoprolin die Aspartimid‐Bildung ausgehend von (7) 25,26. Die Verknüpfung der Glycopeptide (6) und (8) gelang dann durch native chemische Ligation.…”

Section: Antivirale Strategienunclassified

Biochemie und Molekularbiologie 2013

2014

Nachr Chem

View full text Add to dashboard Cite

show abstract

Convergent Solid‐Phase Synthesis of N‐Glycopeptides Facilitated by Pseudoprolines at Consensus‐Sequence Ser/Thr Residues

Cited by 36 publications

References 46 publications

Synthesis of granulocyte–macrophage colony-stimulating factor as homogeneous glycoforms and early comparisons with yeast cell-derived material

Synthesis of granulocyte–macrophage colony-stimulating factor as homogeneous glycoforms and early comparisons with yeast cell-derived material

Chemical synthesis of the ATAD2 bromodomain

Biochemie und Molekularbiologie 2013

Contact Info

Product

Resources

About