Search for: All records

The ligation of sterically demanding peptidyl sites such as those involving Val–Val and Val–Pro linkages has proven to be extremely challenging with conventional NCL methods that rely on exogenous thiol additives. Herein, we report an efficient β-thiolactone-mediated additive-free NCL protocol that enables the establishment of these connections in good yield. The rapid NCL was followed by in situ desulfurization. Reaction rates between β-thiolactones and conventional thioesters towards NCL were also investigated, and direct aminolysis was ruled out as a possible pathway. Finally, the potent cytotoxic cyclic-peptide axinastatin 1 has been prepared using the developed methodology. 

Abstract A new family of hydrazone modified cytidine phosphoramidite building block was synthesized and incorporated into oligodeoxynucleotides to construct photoswitchable DNA strands. TheE‐Zisomerization triggered by the irradiation of blue light with a wavelength of 450 nm was investigated and confirmed by¹H NMR spectroscopy and HPLC in the contexts of both nucleoside and oligodeoxynucleotide. The light activatedZform isomer of this hydrazone‐cytidine with a six‐member intramolecular hydrogen bond was found to inhibit DNA synthesis in the primer extension model by usingBstDNA polymerase. In addition, the hydrazone modification caused the misincorporation of dATP together with dGTP into the growing DNA strand with similar selectivity, highlighting a potential G to A mutation. This work provides a novel functional DNA building block and an additional molecular tool that has potential chemical biology and biomedicinal applications to control DNA synthesis and DNA‐enzyme interactions using the cell friendly blue light irradiation.