Studies have shown that depending on the substitution pattern, microtubule (MT)-targeting 1,2,4-triazolo[1,5-a]pyrimidines (TPDs) can produce different cellular responses in mammalian cells that may be due to these compounds interacting with distinct binding sites within the MT structure. Selected TPDs are also potently bioactive against the causative agent of human African trypanosomiasis, Trypanosoma brucei, both in vitro and in vivo. So far, however, there has been no direct evidence of tubulin engagement by these TPDs in T. brucei. Therefore, to enable further investigation of anti-trypanosomal TPDs, a TPD derivative amenable to photoaffinity labeling (PAL) was designed, synthesized, and evaluated in PAL experiments using HEK293 cells and T. brucei. The data arising confirmed specific labeling of T. brucei tubulin. In addition, proteomic data revealed differences in the labeling profiles of tubulin between HEK293 and T. brucei, suggesting structural differences between the TPD binding site(s) in mammalian and trypanosomal tubulin.
- Keywords
- African trypanosomiasis, Trypanosoma brucei, microtubules, photoaffinity labeling, seventh site, triazolopyrimidines, vinca site,
- MeSH
- HEK293 Cells MeSH
- Humans MeSH
- Proteomics MeSH
- Pyrimidines chemistry MeSH
- Mammals metabolism MeSH
- Trypanocidal Agents * chemistry MeSH
- Trypanosoma brucei brucei * metabolism MeSH
- Trypanosomiasis, African * drug therapy MeSH
- Tubulin metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Pyrimidines MeSH
- Trypanocidal Agents * MeSH
- Tubulin MeSH
