title: Synthesis and comparative properties of two amide-generating resin linkers for use in solid phase peptide synthesis.
abstract: 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.
authors.affiliation: Department of Chemistry, University of Chicago, Chicago, IL 60615, USA. dengprotein@uchicago.edu
authors.forename: Fang-Kun
authors.initials: FK
authors.lastname: Deng
authors.forename: Kalyaneswar
authors.initials: K
authors.lastname: Mandal
authors.forename: Sam
authors.initials: S
authors.lastname: Luisier
authors.forename: Stephen B H
authors.initials: SB
authors.lastname: Kent
mesh_terms: D000577:Amides / Q000737:chemistry*; D001559:Benzhydryl Compounds / Q000138:chemical synthesis / Q000737:chemistry; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis*
chemical_list: C030545:4-methylbenzhydrylamine resin; D000577:Amides; D001559:Benzhydryl Compounds; D010455:Peptides; C004531:benzhydrylamine