A Triazole Bioisostere‐Based Approach to Understanding Ceramide Amide Bond Conformation and Function
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.
Authors
- Seonghun Kim
- Hyun Ju Yoo (ORCID: https://orcid.org/0000-0003-2617-444X)
- Sang Kook Lee (ORCID: https://orcid.org/0000-0002-4306-7024)
- Eun Hee Koh (ORCID: https://orcid.org/0000-0003-3829-0384)
- Jaeho Han (ORCID: https://orcid.org/0009-0009-9437-425X)
- Hyunji Lee (ORCID: https://orcid.org/0000-0001-8463-5078)
- Jae Hyun Kim (ORCID: https://orcid.org/0000-0001-8600-5950)
- Mi Jeong Kim (ORCID: https://orcid.org/0000-0003-1610-7649)
Institutions
- Ulsan College (KR)
- Kyungsung University (KR)
- Seoul National University (KR)
- Asan Medical Center (KR)
- New Generation University College (ET)
- University of Ulsan (KR)
- Chung-Ang University (KR)
Publication Details
- Journal
- Chemistry - An Asian Journal
- Published
- 2025-11-14
- DOI
- https://doi.org/10.1002/asia.202500925
- Primary Topic
- Sphingolipid Metabolism and Signaling
- Type
- article
- Field-Weighted Citation Impact
- 0.00