title: A comparison of Boc and Fmoc SPPS strategies for the preparation of C-terminal peptide α-thiolesters: NY-ESO-1 ³⁹Cys-⁶⁸Ala-COSR.
abstract: The synthesis of a polypeptide derived from the cancer testis antigen NY-ESO-1 bearing a C-terminal α-thiolester is described. Employing tert-butyloxycarbonyl solid phase peptide synthesis the thiolester moiety was installed on-resin using a mercaptopropionic acid linker, thereby requiring no post synthetic manipulations and delivering the requisite α-thiolester polypeptide after cleavage from the resin with HF. Several 9-fluorenylmethyloxycarbonyl solid phase peptide synthesis approaches whereby the thiolester was required to be introduced in a post synthesis manner were examined concurrently. These comprised syntheses on two different "safety catch" linkers, an N-alkyl-N-acyl sulphonamide and an N-acyl benzimidazolone wherein the thiolester is generated from an activated precursor. The condensation of a mercaptan with the C-terminal carboxylate in a direct thiolesterification reaction was also examined. When using either of the three 9-fluorenylmethyloxycarbonyl-based approaches, the linear polypeptide could be assembled straightforwardly on the solid phase resin; however, a thiolesterification of the C-terminal carboxyl of the fully side chain protected peptide proved to be the most effective post-assembly method for the installation of the C-terminal thiolester.
authors: School of Chemical Sciences, The University of Auckland, 23 Symonds St, Auckland, 1010, New Zealand; Maurice Wilkins Center for Molecular Biodiscovery, The University of Auckland, Private Bag 92019,, Auckland, 1010, New Zealand; Institute for Innovation in Biotechnology, The University of Auckland, 3A Symonds St, Auckland, 1010, New Zealand.
authors: Paul W R
authors: PW
authors: Harris
authors: Margaret A
authors: MA
authors: Brimble
mesh_terms: D000595:Amino Acid Sequence; D006801:Humans; D010455:Peptides / Q000737:chemistry; D060327:Solid-Phase Synthesis Techniques; D013438:Sulfhydryl Compounds / Q000737:chemistry
chemical_list: D010455:Peptides; D013438:Sulfhydryl Compounds
keywords: Boc SPPS; Fmoc SPPS; NY-ESO-1; ligation; thiolesterification; thiolesters