Ester and hydroxamate analogues of methionyl and isoleucyl adenylates as inhibitors of methionyl-tRNA and isoleucyl-tRNA synthetases.
The structure activity relationship on a series of ester and hydroxamate analogues of methionyl and isoleucyl adenylate has been investigated through introducing linkers between the 1'-position of ribose and adenine surrogates as methionyl-tRNA, and isoleucyl-tRNA synthetase inhibitors, respectively. The results indicate that ester analogue 23 was found to be a potent inhibitor of Escherichia coli methionyl-tRNA synthetase, and its interaction with the active site was proposed by a molecular modeling study.
Lee
J
J
Laboratory of Medicinal Chemistry, College of Pharmacy, Seoul National University, Kwanak-Ku, South Korea. jeewoo@snu.ac.kr
Kang
S U
SU
Kim
S Y
SY
Kim
S E
SE
Kang
M K
MK
Jo
Y J
YJ
Kim
S
S
D000241:Adenosine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D000249:Adenosine Monophosphate / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D001665:Binding Sites / Q000502:physiology; D004926:Escherichia coli; D004952:Esters / Q000138:chemical synthesis; D006877:Hydroxamic Acids / Q000138:chemical synthesis; D007532:Isoleucine / Q000138:chemical synthesis; D007533:Isoleucine-tRNA Ligase / Q000037:antagonists & inhibitors*; D008715:Methionine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D008718:Methionine-tRNA Ligase / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D013329:Structure-Activity Relationship
D004952:Esters; D006877:Hydroxamic Acids; D007532:Isoleucine; C011501:methioninyl adenylate; D000249:Adenosine Monophosphate; D008715:Methionine; D008718:Methionine-tRNA Ligase; D007533:Isoleucine-tRNA Ligase; D000241:Adenosine