Synthesis of cyclic di-nucleotidic acids as potential inhibitors targeting diguanylate cyclase.
Five analogs of cyclic di-nucleotidic acid including c-di-GMP were synthesized and evaluated for their biological activities on Slr1143, a diguanylate cyclase of Synechocystis sp. Slr1143 was overexpressed from the recombinant plasmid which contained the gene of interest and subsequently purified by affinity chromatography. A new HPLC method capable of separating the compound and product peaks with good resolution was optimized and applied to the analysis of the compounds. Results obtained show that cyclic di-inosinylic acid 1b demonstrates a stronger inhibition on Slr1143 than c-di-GMP and is a potential inhibitor for biofilm formation.
Ching
Shi Min
SM
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543, Singapore.
Tan
Wan Jun
WJ
Chua
Kim Lee
KL
Lam
Yulin
Y
D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D018441:Biofilms / Q000187:drug effects; D002846:Chromatography, Affinity; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D029968:Escherichia coli Proteins; D019761:Phosphorus-Oxygen Lyases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011685:Purine Nucleotides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism; D046939:Synechocystis / Q000201:enzymology
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D011685:Purine Nucleotides; D011994:Recombinant Proteins; C554528:cyclic(3'-5')diinosylic acid; C062025:bis(3',5')-cyclic diguanylic acid; D019761:Phosphorus-Oxygen Lyases; C060720:diguanylate cyclase; D006152:Cyclic GMP