Edited by Renee Tsolis
Keywords:Phosphothreonine lyase Mitogen-activated protein kinase Cross-linking Dehydroalanine Inhibit Effector a b s t r a c tThe phosphothreonine lyases OspF and SpvC irreversibly inactivate host dual-phosphorylated mitogen-activated protein kinases (MAPKs) [pThr-X-pTyr motif] through b-elimination. We found that dual-phosphorylated (pSer-X-pTyr) MAPK substrate peptides and their resulting catalytic products cross-link to OspF and SpvC. Mass spectrometry results revealed that these linkages form between lysine, which acts as a general base, and dehydroalanine (Dha) on catalytic products. The nucleophilic addition efficiency is dependent on the K136 residue being in a deprotonated state. Peptide cross-linking inhibits the activity of SpvC and blocks the inactivation of MAPK signaling by SpvC. Small compounds mimicking these sequences may act as phosphothreonine lyase inhibitors.
A series of bicyclic furo[2,3-d]pyrimidine nucleosides conjugated with N-diisopropylphosphoryl amino acids were synthesized from 2′-deoxy-5-iodouridine. The key step is its cross coupling with the 5-phthalimido-1-pentyne under Sonogashira reaction condition. 5-Endo-dig electrophilic cyclization catalyzed by AgNO3 is used to afford the furo[2,3-d]pyrimidines.
1,2,3-Triazole linked carbohydrate and podophyllotoxin were synthesized in high yield and selectivity. The CuI-catalyzed Huisgen’s [2+3] cycloaddition of azides and alkynes was proved to be powerful tool for constructing podophyllotoxin derivatives.
In this paper, we report an efficient total synthesis of 5-deoxytoyocamycin, which was isolated from microbial sources with excellent antitumor activity. Our synthetic strategy uses 1,2,3-triacetate-5-deoxyribose as the starting material and Vorbrüggen glycosylation as the key step.
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