OER - Kỹ thuật hóa học; Công nghệ sinh học - Thực phẩm; Công nghệ môi trường
Duyệt OER - Kỹ thuật hóa học; Công nghệ sinh học - Thực phẩm; Công nghệ môi trường theo Tác giả "Abegg, Daniel"
Ấn phẩm
Solid Phase Synthesis of Fluorosulfate Containing Macrocycles for Chemoproteomic Workflows
Macrocyclic peptides are attractive for chemoproteomic applications due to their modular
synthesis and potential for high target selectivity. We describe a solid phase synthesis method
for the efficient generation of libraries of small macrocycles that contain an electrophile and
alkyne handle. The modular synthesis produces libraries that can be directly screened using
simple SDS-PAGE readouts and then optimal lead molecules applied to proteomic analysis. We
generated a library of 480 macrocyclic peptides containing the weakly reactive fluorosulfate
(OSF) electrophile. Initial screening of a subset of the library containing each of the various
diversity elements identified initial molecules of interest. The corresponding positional and
confirmational isomers were then screened to select molecules that showed specific protein
labeling patterns that were dependent on the probe structure. The most promising hits were
applied to standard chemoproteomic workflows to identify protein targets. Our results
demonstrate the feasibility of rapid, on-resin synthesis of diverse macrocyclic electrophiles to
generate new classes of covalent ligands.