Unveiling sultam in drug discovery: spotlight on the underexplored scaffold.

Decades ago, the application of cyclic sulfonamide (sultam) and its derivatives primarily focused on their antibacterial properties. However, recent years have seen a shift in research attention towards exploring their potential as anticancer, anti-inflammatory, antidiabetic, and antiviral agents. Despite this broadening scope, only a few sultam drugs have made it to the commercial market, as much of the research on sultams remains in the discovery phase. This class of compounds holds significant promise and remains pertinent in pharmaceutical research. Due to sultam's relevance and growing importance in drug discovery, this review paper aims to consolidate and examine the biological activities of sultam derivatives ranging from 4 to 8-membered ring structures.

Optimizing the Semisynthesis towards glycosylated interferon-ß-polypeptide by utilizing bacterial protein expression and chemical modification.

The synthesis of a sufficient amount of homogeneous glycoprotein is of great interest because natural glycoproteins show considerable heterogeneity in oligosaccharide structures, making the studies on glycan structure-function relationship difficult. Herein, we report optimized methods that can accelerate the semisynthesis of homogeneous glycoproteins based on recombinant expression and chemical conversion. Peptide thioesters and peptides with Cys residues at their N-terminals are necessary intermediates to perform native chemical ligation. We successfully performed thioesterification for a peptide prepared in E. coli via Cys-cyanylation at its C-terminal followed by hydrazinolysis and acidic thiolysis. These optimized conditions could tolerate an acid labile Thz protected Cys at the N-terminal of a peptide-hydrazide and specific cyanylation of the C-terminal Cys to yield a peptide thioester. To reduce the amount of precious oligosaccharide that is required in the conventional SPPS method, an improved liquid phase glycopeptide coupling was also optimized in a good yield (46% over four steps). Lastly, chemoselective protection of the internal cysteines and activation of the N-terminal cysteine were optimized toward a long peptide prepared in E. coli. By using these strategies, a full-length interferon-ß glycosyl polypeptide as a model was successfully obtained.