A new approach to the chemical synthesis of keto-proteins.
To increase the versatility of protein-conjugation, an orthogonal protection strategy is described, which enables the efficient synthesis of keto-proteins bearing a reactive ketone functionality using Boc, Fmoc, and chemical ligation methodologies. A 1,3-dithiolane group was used to protect the ketone function of levulinate- and pyruvate-derivatized peptides during solid-phase synthesis, acidolytic cleavage, and purification. When required, the 1,3-dithiolane group could be cleanly removed using aqueous silver or mercuric solutions to regenerate the reactive keto-protein at ambient temperature. The liberated keto-protein was chemoselectively conjugated in situ to an aminooxy-derivatized monodisperse polymer.
Tumelty
David
D
Gryphon Therapeutics, 600 Gateway Boulevard, South San Francisco, CA 94080, USA.
Carnevali
Maia
M
Miranda
Les P
LP
D000595:Amino Acid Sequence; D018946:Chemokine CCL5 / Q000138:chemical synthesis; D002851:Chromatography, High Pressure Liquid; D007659:Ketones / Q000138:chemical synthesis*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis; D011506:Proteins / Q000138:chemical synthesis*
D018946:Chemokine CCL5; D007659:Ketones; D010446:Peptide Fragments; D011506:Proteins