title: An o-nitrobenzyl scaffold for peptide ligation: synthesis and applications.
abstract: Chemical ligation approaches facilitate the chemoselective assembly of unprotected peptides in aqueous solution. Here, two photolabile auxiliaries are described that enlarge the applicability of native chemical ligation to non-cysteine targets. The auxiliaries, designed to allow reaction with thioester peptides, generate an amide bond between the two initial fragments. The o-nitrobenzyl tertiary benzylamide that is formed at the ligation junction can be transformed into a native amide group under mild photolysis conditions. The veratryl auxiliary was found to be excessively labile during peptide purification and ligation. However, the auxiliary based on the o-nitrobenzyl group shows all the necessary properties for a general application in routine peptide and protein synthesis. In addition, the auxiliary linked to the N-terminus can be efficiently photolyzed, suggesting a new approach for the generation of photocaged amines. Synthesis, solid phase introduction onto peptide chains, ligation properties and photolysis in water are described, and a careful study of compatibility of the method with potentially fragile peptide side chains is reported.
authors.affiliation: Istituto di Chimica del Riconoscimento Molecolare, CNR, Milano, Italy. chiara.marinzi@icrm.cnr.it
authors.forename: Chiara
authors.initials: C
authors.lastname: Marinzi
authors.forename: John
authors.initials: J
authors.lastname: Offer
authors.forename: Renato
authors.initials: R
authors.lastname: Longhi
authors.forename: Philip E
authors.initials: PE
authors.lastname: Dawson
mesh_terms: D009578:Nitrobenzenes / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D010782:Photolysis; D012996:Solutions / Q000737:chemistry
chemical_list: D009578:Nitrobenzenes; D010455:Peptides; D012996:Solutions