title: Evaluation of COMU as a coupling reagent for in situ neutralization Boc solid phase peptide synthesis.
abstract: Benzotriazole-based coupling reagents have dominated the last two decades of solid phase peptide synthesis. However, a growing interest in synthesizing complex peptides has stimulated the search for more efficient and low-cost coupling reagents, such as COMU which has been introduced as a nonexplosive alternative to the classic benzotriazole coupling reagents. Here, we present a comparative study of the coupling efficiency of COMU with the benzotriazole-based HBTU and HCTU for use in in situ neutralization Boc-SPPS. Difficult sequences, such as ACP(65-74), Jung-Redeman 10-mer, and HIV-1 PR(81-99), were used as model target peptides on polystyrene-based resins, as well as polyethylene glycol-based resins. Coupling yields obtained using fast in situ Boc-SPPS cycles were determined with the quantitative ninhydrin test as well as via LC-MS analysis of the crude cleavage products. Our results demonstrate that COMU coupling efficiency was less effective compared to HBTU and HCTU with HCTU ≥ HBTU > COMU, when polystyrene-based resins were employed. However, when the PEG resin was employed in combination with a safety catch amide (SCAL) linker, more comparable yields were observed for the three coupling reagents with the same ranking HCTU ≥ HBTU > COMU.
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St Lucia, 4072, Australia.
authors.forename: Claudia U
authors.initials: CU
authors.lastname: Hjørringgaard
authors.forename: Andreas
authors.initials: A
authors.lastname: Brust
authors.forename: Paul F
authors.initials: PF
authors.lastname: Alewood
mesh_terms: D003432:Cross-Linking Reagents; D005563:Formic Acid Esters; D012117:Resins, Synthetic; D060327:Solid-Phase Synthesis Techniques / Q000379:methods*
chemical_list: D003432:Cross-Linking Reagents; D005563:Formic Acid Esters; D012117:Resins, Synthetic; C000345:t-butyloxycarbonyl group