Abstract
Lanthanide(III) ions can accelerate the hydrolysis of phosphomonoesters and phosphodiesters in neutral aqueous solution. In this paper, lanthanide-mediated dephosphorylation has been applied in aqueous media as an orthogonal cleavage condition that can be employed in conventional solid phase peptide synthesis (SPPS). A phosphorylated polymeric support for SPPS was developed using Boc chemistry. The cleavage of resin-bound phosphates was investigated with the addition of Eu(III), Yb(III), acid or base, a mixture of solvents or different temperatures. To demonstrate the utility of this approach for SPPS, a peptide sequence was synthesized on a phosphorylated polymeric support and quantitatively cleaved with lanthanide ions in neutral aqueous media. The protecting groups for side chains were retained during peptide cleavage using lanthanide ions. This new methodology provides a mild orthogonal cleavage condition of phosphoester as a linker during SPPS.
Highlights
The ligand complexes of some lanthanide(III) ions can mediate the hydrolysis of phosphomonoesters and phosphodiesters in aqueous or organic solutions [1,2,3,4,5,6]
To expand the choice of orthogonal deprotection and cleavage methods for solid phase peptide synthesis (SPPS), we investigated the use of a phosphoric ester as a peptide-resin linker and lanthanide(III)-mediated dephosphorylation in neutral aqueous media as a final peptide harvesting method
The phosphate loaded resin was very stable in 50% trifluoroacetic acid (TFA) in CH2Cl2, so we investigated the utility of this resin for Boc-SPPS (Scheme 1)
Summary
The ligand complexes of some lanthanide(III) ions can mediate the hydrolysis of phosphomonoesters and phosphodiesters in aqueous or organic solutions [1,2,3,4,5,6]. Boc-SPPS requires very strong acids to cleave the peptide from the resin, which limits strategies available for selective deprotection of specific side chains. To avoid these problems with acid- and base-labile chemistries, some linkers have been developed for SPPS that can be cleaved using reducing agents, UV light, ultrasonication or fluoride [17,18,19,20]. To expand the choice of orthogonal deprotection and cleavage methods for SPPS, we investigated the use of a phosphoric ester as a peptide-resin linker and lanthanide(III)-mediated dephosphorylation in neutral aqueous media as a final peptide harvesting method
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