Structure-activity relationship studies of salubrinal lead to its active biotinylated derivative.
The synthesis and structure-activity relationships (SAR) of salubrinal, a small molecule that protects cells from apoptosis induced by endoplasmic reticulum (ER) stress, are described. It is revealed that the trichloromethyl group greatly contributes to the activity. Based on the SAR results, salubrinal was converted into a biotinylated derivative which retains activity and can be used as a biological tool for target identification.
Long
Kai
K
State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, China.
Boyce
Michael
M
Lin
He
H
Yuan
Junying
J
Ma
Dawei
D
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019921:Biotinylation; D002470:Cell Survival / Q000187:drug effects; D002934:Cinnamates / Q000138:chemical synthesis* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016716:PC12 Cells; D020011:Protective Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
D002934:Cinnamates; D020011:Protective Agents; C496827:salubrinal; D013890:Thiourea