title: Screening of N-alkyl-cyanoacetamido oximes as substitutes for N-hydroxysuccinimide.
abstract: Peptide-bond formation is a pivotal process in the synthesis of peptide oligomers. Among the various coupling methodologies described, carbodiimides combine strong acylation potency and smooth reaction conditions, and they are commonly used in the presence of N-hydroxylamine additives. In recent years, acidic oxime templates, mainly ethyl 2-cyano-2-(hydroxyimino) acetate (Oxyma), have emerged as highly reactive alternatives to the classic and explosive-prone benzotriazolic additives, 1-hydroxybenzotriazole (HOBt) and 1-hydroxy-7-azabenzotriazole (HOAt). However, to achieve certain biochemical targets, less reactive species, such as N-hydroxysuccinimide (HOSu) esters, are often required to obtain stability under aqueous conditions. In the present study, we report on a new family of water-soluble N-alkyl-cyanoacetamido oximes, most of which have proven useful in the construction of active carbonates for the introduction of fluorenylmethoxycarbonyl (Fmoc) with minimal impact of dipeptide impurities. We performed a direct comparison of these new N-alkyl-cyanoacetamido oximes with HOSu in order to evaluate their capacity to retain optical purity and their coupling efficiency in the assembly of bulky residues.
authors.affiliation: Department of Chemistry, Faculty of Science, University of Alexandria P.O. Box 246, Ibrahimia, 21321 Alexandria (Egypt) E-mail: aymanel_faham@hotmail.com.
authors.forename: Sherine N
authors.initials: SN
authors.lastname: Khattab
authors.affiliation: Department of Chemistry and Molecular Pharmacology, Institute for Research in Biomedicine Barcelona Science Park, Baldiri Reixac 10, 08028 Barcelona (Spain) E-mail: albericio@irbbarcelona.org ; CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine Barcelona Science Park, Baldiri Reixac 10, 08028 Barcelona (Spain).
authors.forename: Ramon
authors.initials: R
authors.lastname: Subirós-Funosas
authors.affiliation: Department of Chemistry, Faculty of Science, University of Alexandria P.O. Box 246, Ibrahimia, 21321 Alexandria (Egypt) E-mail: aymanel_faham@hotmail.com ; Department of Chemistry and Molecular Pharmacology, Institute for Research in Biomedicine Barcelona Science Park, Baldiri Reixac 10, 08028 Barcelona (Spain) E-mail: albericio@irbbarcelona.org ; Department of Chemistry, College of Science, King Saud University P.O.Box 2455, 11451 Riyadh (Kingdom of Saudi Arabia).
authors.forename: Ayman
authors.initials: A
authors.lastname: El-Faham
authors.affiliation: Department of Chemistry and Molecular Pharmacology, Institute for Research in Biomedicine Barcelona Science Park, Baldiri Reixac 10, 08028 Barcelona (Spain) E-mail: albericio@irbbarcelona.org ; CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine Barcelona Science Park, Baldiri Reixac 10, 08028 Barcelona (Spain) ; Department of Organic Chemistry, University of Barcelona Martí i Franqués 1-11, 08028 Barcelona (Spain) ; School of Chemistry, University of KwaZulu-Natal 4041 Durban (South Africa).
authors.forename: Fernando
authors.initials: F
authors.lastname: Albericio
keywords: N-hydroxysuccinimides; additives; oximes; peptide syntheses; peptide-bond formations