Light-Cleavable Rapamycin Dimer as a Universal Optical Trigger for Protein Dimerization
نویسندگان
چکیده
The synthetic scheme is shown in Supporting Figure S1 and the NMR spectra of new compounds are shown in Supporting Figures S2-S3. In short, rapamycin was acylated with the N-succinimidyl carbonate 1 according to a literature procedure that enables selective modification of the C40 position, yielding the caged rapamycin monomer 2 in 45% yield. This yield is comparable to other reported modifications of rapamycin. The tethered triple bond in 2 was then used in a highly efficient double [3+2] cycloaddition reaction with 1,4-diazidobutane in the presence of CuSO4, sodium ascorbate, and tris[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]amine (TBTA), delivering the rapamycin dimer dRap in 85% yield.
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