A Triazole Bioisostere-Based Approach to Understanding Ceramide Amide Bond Conformation and Function

초록

The amide bond of ceramide can adopt either a cis or trans conformation, but the biological relevance of this geometry remains unclear. We used 1,4- and 1,5-disubstituted 1,2,3-triazoles as conformationally restricted bioisosteres to investigate the functional consequences of amide bond geometry. Antiproliferative assays, sphingomyelin synthase 1 metabolite profiling, and molecular docking analyses all indicate that the trans conformation better reflects the biologically active state. These findings provide direct evidence that amide bond conformation plays a critical role in ceramide function. © 2025 Wiley‐VCH GmbH.

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