iProXProteomicsHan WeiHomo Sapienshttp://www.iprox.org/page/project.html?id=IPX0017330000weihan548@126.comZhengzhou UniversityiProXfalseChemoproteomic profiling of SGPP-binding proteinsS-guanylation is an endogenous post translational modification that has been implicated as a specific autophagic signal, yet its molecular mechanism and the identity of its binding proteins remain largely unknown. Here, we developed the first diazirine based photoaffinity probe for S-guanylation (SGPP) to capture and identify its interacting proteins in living cells. The SGPP efficiently labeled target proteins in a time , concentration , and UV crosslinking dependent manner, as demonstrated by in gel fluorescence scanning. Competitive labeling with excess FBnG, a known AUTAC warhead, confirmed the specificity of the probe. Using a chemoproteomic workflow combining SGPP mediated photocrosslinking, affinity enrichment, and mass spectrometry, we identified candidate binding proteins in HeLa cellsThu May 21 00:00:00 BST 2026PXD0786619606