title: Design, synthesis and structure-activity relationship of novel Relacin analogs as inhibitors of Rel proteins.
abstract: Rel proteins in bacteria synthesize the signal molecules (p)ppGpp that trigger the Stringent Response, responsible for bacterial survival. Inhibiting the activity of such enzymes prevents the Stringent Response, resulting in the inactivation of long-term bacterial survival strategies, leading to bacterial cell death. Herein, we describe a series of deoxyguanosine-based analogs of the Relacin molecule that inhibit in vitro the synthetic activity of Rel proteins from Gram positive and Gram negative bacteria, providing a deeper insight on the SAR for a better understanding of their potential interactions and inhibitory activity. Among the inhibitors evaluated, compound 2d was found to be more effective and potent than our previously reported Relacin.
authors.affiliation: Institute for Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Ezequiel
authors.initials: E
authors.lastname: Wexselblatt
authors.forename: Ilana
authors.initials: I
authors.lastname: Kaspy
authors.forename: Gad
authors.initials: G
authors.lastname: Glaser
authors.forename: Joshua
authors.initials: J
authors.lastname: Katzhendler
authors.forename: Eylon
authors.initials: E
authors.lastname: Yavin
mesh_terms: D034301:Deinococcus / Q000737:chemistry; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004151:Dipeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004926:Escherichia coli / Q000737:chemistry; D015394:Molecular Structure; D020569:Proto-Oncogene Proteins c-rel / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D013329:Structure-Activity Relationship
chemical_list: D004151:Dipeptides; D020569:Proto-Oncogene Proteins c-rel; C580565:relacin; D003849:Deoxyguanosine
keywords: (p)ppGpp; Antibacterial; Purine; RelA; Stringent Response