TOMBU and COMBU as Novel Uronium-Type Peptide Coupling Reagents Derived from Oxyma-B

Abstract

Abstract: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 OPEN ACCESSMolecules 2014, 19 18954 HBTU in terms of preserving chiral integrity and coupling yields, but slightly worse performance than COMU.

Easy parallel screening of reagent stability, quality control, and metrology in solid phase peptide synthesis (SPPS) and peptide couplings for microarrays

“…Although nuclear magnetic resonance (NMR) spectroscopy can establish reagent purity, the technique can miss certain impurities. As shown here, ultraviolet (UV) absorption spectroscopy reported previously with high performance liquid chromatography (HPLC) was not an index of the molecular integrity of COMU. Likewise, chromogenic reactions of COMU studied here in detail were not indicative of COMU stability either.…”

“…These factors become important because COMU can be purchased from several vendors, sometimes without purity data. Finally, there were contradictory reports regarding COMU solution stability under various storage conditions as discussed in detail later in this paper.…”

“…The screening data of COMU stability (Figure ) was supported by Tofteng et al who found that COMU dissolved in DMF and stored in open vials had a half life of 3 h, and after 24 h no peptide synthesis would occur. Jad et al confirmed that COMU solution stability in DMF was reduced by >50% after 4 h in a closed vessel. Stability further dropped to 3 and 0% after 24 and 48 h, respectively, confirming the data of Figure .…”

“…Ultraviolet absorption spectroscopy was used to monitor COMU during HPLC . The UV absorption maxima of COMU was 272 nm in DMF and NMP.…”

Peptide Coupling Reactions

“…In addition, Oxyma-B performs better as a racemization suppressor than Oxyma Pure and even better than HOAt in both stepwise and segment coupling in solid-and solution-phase peptide synthesis [28]. Lately,a new class of O-form uronium-type coupling reagents derived from Oxyma-B were introduced TOMBU and COMBU ( Figure 5) [29]. …”