Papers by Christian Haase
In this thesis approaches for convergent synthesis of peptides have been developed. In the extend... more In this thesis approaches for convergent synthesis of peptides have been developed. In the extended native chemical ligation so far space demanding auxiliaries encumbered challenging condensations. Furthermore the required drastic acidolytic cleavage conditions were furthermore incompatible with many post-translational modifications. In the thesis a nouvelle less space demanding scaffold was scrutinized which allowed a milder basic cleavage. Therefore a small electron-accepting substituent was introduced that enabled the induction of an elimination reaction liberating the target peptide after the peptide ligation had taken place. Furthermore the applicability of the commercially available penicillamine as precursor of valine in the ligation-desulfurization strategy could be demonstrated. Finally the ligation with sequence internal cysteines was scrutinized. Herein it could be shown that certain peptides with cysteine in a distinctive position of the sequence preferable reacted in thioester-based condensation reactions.
Topics in Current Chemistry, 2006
Despite its omnipresence in nature, comparatively little is known about how glycosylation affects... more Despite its omnipresence in nature, comparatively little is known about how glycosylation affects the function and activity of proteins. To understand the role of protein glycosylation at the molecular level, it is important to have access to homogeneous glycoproteins and glycopeptides. Chemical synthesis is particularly suited to provide uniform glycoprotein material, thus playing a pivotal role for the advancement of glycobiology. This chapter summarizes the recent progress achieved in glycopeptide synthesis including new glycosylation methods, enzymatic transformations, chemoselective ligation and recombinant expression.
Tetrahedron Letters, 2012
Unwanted trifluoroacetylation occurred at the N-terminus of prolinyl peptides during detachment f... more Unwanted trifluoroacetylation occurred at the N-terminus of prolinyl peptides during detachment from the solid phase. This was observed when the N-a-Fmoc protecting group had been removed prior to the final TFA treatment. Subtly changing the SPPS protocol and incorporating Boc-in place of the Fmoc-protected proline as the N-terminal building block efficiently suppressed this side reaction.
Synlett, 2005
The reaction of γ-alkylidenebutenolides, readily available by cyclization of 1,3-bis-silyl enol e... more The reaction of γ-alkylidenebutenolides, readily available by cyclization of 1,3-bis-silyl enol ethers with oxalyl chloride, with amines in glacial acetic acid allows a convenient synthesis of 5-alkylidene-2,5-dihydropyrrol-2-ones. This method was applied to a formal total synthesis of the natural product pukeleimide A.
European Journal of Organic Chemistry, 2009
Thioester-mediated peptide coupling reactions are powerful tools in protein synthesis. The fragme... more Thioester-mediated peptide coupling reactions are powerful tools in protein synthesis. The fragment coupling occurs extremely fast at ligation sites that contain an N-terminal cysteine residue. This native chemical ligation involves a capture step that affixes the acyl component in the immediate vicinity of the N-terminal amino group. The subsequent intramolecular S,N-acyl transfer step proceeds via an entropically favored five-membered ring intermediate. In this study we investigated whether sequence internal cysteine residues that lead to the formation of macrocyclic intermediates are also able to accelerate the rate of thioester-based fragment couplings. It was the aim to identify distance requirements that enable internal cysteine-mediated ligation reactions to proceed at synthetically useful rates. It was found that appropriately positioned cysteine residues can induce up to 25-fold rate enhancements compared to a cysteine-lacking control peptide. Highest ligation rates and yields were obtained when the internal thiol amino acid was incorporated at the fifth or sixth position from the N-terminus of the C-terminal coupling segment. The findings reveal a correlation between the size of the macrocyclic ring intermediate and the ease of the peptide ligation. Internal cysteine ligation may provide the opportunity to shift amino acid cysteine bonds that are difficult to access through native chemical ligation (such as Pro–Cys bonds) by 4–5 amino acids to the N-terminus.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Chemistry - A European Journal, 2012
Angewandte Chemie International Edition, 2008
Angewandte Chemie International Edition, 2008
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Papers by Christian Haase