Development of an oxazole-based cleavable linker for peptides.

We report the development of a new oxazole-based cleavable linker to release peptides from attached cargo. Oxazoles are stable to most reaction conditions, yet they can be rapidly cleaved in the presence of single-electron oxidants like cerium ammonium nitrate (CAN). An oxazole linker could be synthesized and attached to peptides through standard solid-phase peptide coupling reactions. Cleavage of these peptide-oxazole conjugates is demonstrated on a broad scope of peptides containing various natural and unnatural amino acids. These results represent the first example of a peptide-based linker that is cleaved through single-electron oxidation. The oxazole is also demonstrated to be a suitable linker for both the release of a peptide from a conjugated small molecule and the orthogonal release of cargo from a peptide containing multiple cleavable linkers. Oxazole linkers could serve as a promising tool for peptide screening platforms such as peptide-encoded libraries.

Biliary Intraepithelial Neoplasia With Gallbladder Adenoma and Cirrhosis: A Case Report.

Biliary intraepithelial neoplasia (BilIN) is a precursor lesion of cholangiocarcinoma that has been rarely reported. The present study reports a 56-year-old male with low-grade BilIN of the bile ducts and the cystic duct margin. Stent exchange endoscopy demonstrated an irregular, intraductal mass extending along the common bile duct, common hepatic duct, and hepatic duct bifurcation. The peribiliary mass was found to abut the right portal vein, inferior vena cava, and pancreatic head, and replaced the right hepatic artery. In addition, there was evidence of gallbladder adenoma managed with cholecystectomy and a right-lobed liver lesion and cirrhosis, which prompted the discussion of prophylactic liver transplantation. We emphasize the radiological features of BilIN and associated pathological findings through multiple imaging modalities. Consideration of this diagnosis is indicated in western countries and requires timely management based on available guidelines.