K-Oxyma: a Strong Acylation-Promoting, 2-CTC Resin-Friendly Coupling Additive (original) (raw)
Related papers
Oxime ligation in acetic acid: efficient synthesis of aminooxy-peptide conjugates
Journal of peptide science : an official publication of the European Peptide Society, 2017
Oxime ligation is a powerful tool in various bioconjugation strategies. Nevertheless, high reaction rates and quantitative yields are typically reported for aldehyde-derived compounds. In contrary, keto groups react much slower, with quantitative yields achieved at 5 h for low-molecular weight compounds and more than 15 h for polymers or dendrimers. In this communication, we report that oxime ligation proceeds rapidly with quantitative (>95%) conversion within 1.5-2 h in pure acetic acid. The practical utility of suggested technique is illustrated by the synthesis of peptide-steroid and peptide-polymer conjugates of model aminooxy-peptides. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.
Recent development in peptide coupling reagents
Journal of Saudi Chemical Society, 2011
Two decades of domination of benzotriazole-based chemistry stimulated the progress in peptide synthesis to a high level of effectiveness. However, the growing need for new and more complex peptide structures, particularly for biomedical studies and, very recently, for the large-scale production of peptides as drugs, required manufacturing peptide products by efficient synthetic strategies, at reasonably low prices. Therefore, the search for new, more versatile and low-cost reagents becomes a great challenge. Several comprehensive review articles summarized the great effort undertaken, but up to now, no versatile coupling reagent useful for both amide and ester bond formation, as well as for solution and solid-phase peptide synthesis has been yet developed. The most-widely used coupling reagents are carbodiimides on one hand and phosphonium and aminium salts on the other. Herein in this review article, we summarized the recent development in peptide coupling reagents during the last two decades.
Benzhydrylamine linker grafting: a strategy for the improved synthesis of C‐terminal peptide amides
Journal of Peptide Science, 2010
The standard p‐MBHA resin used during Boc‐chemistry synthesis of peptides carrying C‐terminal carboxamides is compromised by batch‐to‐batch variations in its performance. This can cause artificially ‘difficult’ couplings during peptide chain assembly, which may ultimately lead to failed syntheses given the inability to achieve acceptable coupling yields. To overcome these problems, we have developed a new approach by grafting a functionalized benzhydrylamine linker onto well‐characterized and well‐performing PAM resins. We combine optimized Boc‐chemistry, high‐performing PAM resins and new benzhydrylamine‐based linkers to achieve improved syntheses of peptide amides. Here we present the synthesis of two new benzhydrylamine linkers and their attachment to selected PAM resins. This novel solid support was evaluated through the synthesis of selected ‘difficult’ conotoxins and monitoring the coupling efficiency using quantitative ninhydrin assay. The results show a superior performance ...
Journal of Peptide Science, 2014
Stand-alone coupling reagents derived from bis(2-oxo-3-oxazolidinyl)phosphorodiamidic chloride show efficient performance in solution and SPPS. In particular, the Oxyma Pure (Luxembourg Biotech., Tel Aviv, Israel) derivative shows the additional advantage of being highly soluble in DMF and even fairly soluble in CH 3 CN, which can extend its use for the synthesis of complex peptides. These new stand-alone coupling reagents have the advantage of not bearing any counteranion such as PF 6 or BH 4 , whose presence can jeopardize the purification of final peptides prepared in solution.
TOMBU and COMBU as Novel Uronium-Type Peptide Coupling Reagents Derived from Oxyma-B
Molecules, 2014
Here we describe two novel uronium salts, TOMBU and COMBU, derived from the recently described Oxyma-B for use in peptide bond synthesis. These coupling reagents are more stable than COMU in DMF. Furthermore, using various peptide synthetic models in solution and solid-phase synthesis, we reveal that they show better performance than
Oxyma-based phosphates for racemization-free peptide segment couplings
Journal of peptide science : an official publication of the European Peptide Society, 2016
Glyceroacetonide-Oxyma [(2,2-dimethyl-1,3-dioxolan-4-yl)methyl 2-cyano-2-(hydroxyimino)acetate (1)] displayed remarkable physico-chemical properties as an additive for peptide-forming reactions. Although racemization-free amide-forming reactions have been established for N-urethane-protected α-amino acids with EDCI, 1, and NaHCO3 in water or DMF-water media, amide-forming reactions of N-acyl-protected α-amino acids and segment couplings of oligopeptides still require further development. Diethylphosphoryl-glyceroacetonide-oxyma (DPGOx 3) exhibits relative stability in aprotic solvents and is an effective coupling reagent for N-acyl-protected α-amino acids and oligo peptide segments. The conditions reported here is also effective in lactam-forming reactions. Unlike most of the reported coupling reagents, simple aqueous work-up procedures can remove the reagents and by-products generated in the reactions.
Journal of Peptide Science, 2010
Well-characterized resins of high purity are critical for effective solid phase peptide synthesis (SPPS). The quality of commercial (4-methyl)benzhydrylamine-resin (MBHA-resin), used for the synthesis of peptide amides, is not consistent and residual ketone functionalities are frequently present. Such ketone or aldehyde impurities lead to the formation of acylation-resistant deletion peptides in SPPS. To avoid these undesirable side reactions, we have optimized the preparation of two amide-generating linkers, which, in combination with aminomethyl-resin prepared directly from polystyrene resin, serve as alternatives to MBHA-resin for peptide amide synthesis. Then we have explored their comparative properties in SPPS. Use of sonication in reductive amination facilitated the synthesis of both benzhydrylamine (BHA) and MBHA linkers.