Acid-Mediated Prevention of Aspartimide Formation in Solid Phase Peptide Synthesis

Michels, Tillmann; Dölling, R.; Haberkorn, Uwe; Mier, Walter

doi:10.1021/ol3007925

Cited by 64 publications

(62 citation statements)

References 20 publications

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“…24,25 Although N-hydroxylamine derivatives such as HOBt are known to be effective as buffers, we found it particularly economical to use formic acid, as reported by Mier. 26 Changing the deprotection solution from 80/20 DMF/piperidine to 80/19/1 DMF/piperidine/HCOOH for all deblock steps following aspartate incorporation, aspartimide formation was prevented without any obvious decrease in Fmoc deprotection efficiency.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of multivalent glycopeptide conjugates that mimic an HIV epitope

et al. 2016

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Recently, we reported a directed evolution method which enabled us to discover sequences of glycopeptides that bind with picomolar affinity to HIV antibody 2G12 and are of interest as HIV vaccine candidates. In this manuscript, we describe the syntheses of several of these large (~11–12 kDa) glycopeptides by a combination of fast flow peptide synthesis and click chemistry. We also discuss the optimization of their attachment to carrier protein CRM197, affording antigenic and immunogenic conjugates ready for animal vaccination.

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Section: Resultsmentioning

confidence: 99%

Synthesis of multivalent glycopeptide conjugates that mimic an HIV epitope

et al. 2016

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“…Since deprotection by hydrolysis in basic conditions led to aspartimide formation and resulted in a mixture of both the carboxylic acid ( 15 ) and primary amide side chain ( 14 b ), addition of formic acid (1.4 equiv., 0.2 equiv. with respect to LiOH) was mandatory to avoid this side reaction 25…”

Section: Resultsmentioning

confidence: 99%

Suzuki–Miyaura Diversification of Amino Acids and Dipeptides in Aqueous Media

et al. 2015

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The Suzuki-Miyaura derivatisation of free amino acids, peptides and proteins is an attractive area with much potential utility for medicinal chemistry and chemical biology. Here we report the modification of unprotected and Boc-protected aromatic amino acids and dipeptides in aqueous media, enabling heteroarylation and vinylation. We systematically investigate the impact of the peptide backbone and adjacent amino acid residues upon the reaction. Our studies reveal that whilst asparagine and histidine hinder the reaction, by utilising dppf, a ferrocene-based bidentate phosphine ligand, cross-coupling of halophenylalanine or halotryptophan adjacent to such a residue could be enabled. Our studies reveal dppf to have good compatibility with all unprotected, proteinogenic amino acid side chains.

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“…Using microwave-SPPS and piperazine (5% piperazine with 0.1 M HOBt in DMF), the amount of aspartimide by-products observed during the synthesis of H-VYWTSPFMKLIHEQCNRADG-NH 2 was reduced from 32% to 3% [58]. More recently, it was demonstrated that the addition of Oxyma [77] and acids such as formic acid [78] to the Fmoc cleavage solution could also suppress the formation of aspartimide by-products. For example, in the presence of formic acid (5 vol.% to piperidine), aspartimide formation , was reduced by around 90% [78].…”

Section: Methods For the Synthesis Of Long/difficult Peptidesmentioning

confidence: 99%

“…More recently, it was demonstrated that the addition of Oxyma [77] and acids such as formic acid [78] to the Fmoc cleavage solution could also suppress the formation of aspartimide by-products. For example, in the presence of formic acid (5 vol.% to piperidine), aspartimide formation , was reduced by around 90% [78].…”

Section: Methods For the Synthesis Of Long/difficult Peptidesmentioning

confidence: 99%

New Methods for Chemical Protein Synthesis

Guan

Chaffey

Zeng

2014

Topics in Current Chemistry

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Chemical protein synthesis is a useful tool to generate pure proteins which are otherwise difficult to obtain in sufficient amounts for structure and property analysis. Additionally, because of the precise and flexible nature of chemical synthesis, it allows for controllable variation of protein sequences, which is valuable for understanding the relationships between protein structure and function. Despite the usefulness of chemical protein synthesis, it has not been widely adopted as a tool for protein characterization, mainly because of the lack of general and efficient methods for the preparation and coupling of peptide fragments and for the folding of polypeptide chains. To address these issues, many new methods have recently been developed in the areas of solid-phase peptide synthesis, peptide fragment assembly, and protein folding. Here we review these recent technological advances and highlight the gaps needing to be addressed in future research.

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Acid-Mediated Prevention of Aspartimide Formation in Solid Phase Peptide Synthesis

Cited by 64 publications

References 20 publications

Synthesis of multivalent glycopeptide conjugates that mimic an HIV epitope

Synthesis of multivalent glycopeptide conjugates that mimic an HIV epitope

Suzuki–Miyaura Diversification of Amino Acids and Dipeptides in Aqueous Media

New Methods for Chemical Protein Synthesis

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