Orthogonal Cleavage of the HMPB Linker from Solid Support Using HFIP
The Pentelute Lab aims to invent new chemistry for the efficient and selective modification of proteins, to ‘hijack’ these biological machines for efficient drug delivery into cells and to create new machines to rapidly and efficiently manufacture peptides and proteins.
Pentelute Lab, Chemistry, MIT, Chemistry Department, Boston, Cambridge, Biology, Peptides, Peptide, Proteins, Science, Rapid, Brad Pentelute, Brad,
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Orthogonal Cleavage of the HMPB Linker from Solid Support Using HFIP
Orthogonal Cleavage of the HMPB Linker from Solid Support Using HFIP
Michael DesgagnéDennis A. Kutateladze, Bradley L. Pentelute*
Abstract
Hexafluoroisopropanol (HFIP) is widely used as a hydrogen-bond-donor solvent. Here we demonstrate that 4-(4-hydroxymethyl-3-methoxyphenoxy)butyric acid (HMPB), a commonly used linker for generating C-terminal carboxylic acid peptides, cleaves from the solid support at HFIP concentrations as low as 20% in dichloromethane. The resulting yields are comparable to concentrated trifluoroacetic acid cleavage conditions. This reactivity is attributed to an added resonance structure, enabled by a p-methoxy substituent, which potentially stabilizes the benzylic carbocation intermediate during cleavage.
Category
2025, Publications
