Automated allyl cleavage for continuous-flow synthesis of cyclic and branched peptides.
An automated allyl cleavage scheme on a continuous-flow peptide synthesizer was used for the preparation of "head-to-tail" cyclic peptides, branched peptides, and multiple antigenic peptides. Standard allyl removal uses a suspended palladium catalyst. This approach is not feasible on a batch and continuous-flow peptide synthesizer due to problematic delivery of the insoluble palladium catalyst. Solvent conditions were examined and optimized to solubilize the catalyst, prevent undesired Fmoc deblocking and be compatible with sensitive amino acids (Trp and Met) and with glyco- and sulfopeptides. Protocols for a continuous-flow peptide synthesizer were modified using new conditions to carry out the allyl cleavage scheme for the facile preparation of complex peptides.
Kates
S A
SA
Millipore Corporation, Bedford, Massachusetts 01730.
Daniels
S B
SB
Albericio
F
F
D000498:Allyl Compounds / Q000737:chemistry*; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D005449:Fluorenes / Q000737:chemistry; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis*; D010456:Peptides, Cyclic / Q000138:chemical synthesis*; D012116:Resins, Plant
D000498:Allyl Compounds; D000596:Amino Acids; D005449:Fluorenes; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; D010455:Peptides; D010456:Peptides, Cyclic; D012116:Resins, Plant