title: Synthesis of cyclic di-nucleotidic acids as potential inhibitors targeting diguanylate cyclase.
abstract: 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.
authors.affiliation: Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543, Singapore.
authors.forename: Shi Min
authors.initials: SM
authors.lastname: Ching
authors.forename: Wan Jun
authors.initials: WJ
authors.lastname: Tan
authors.forename: Kim Lee
authors.initials: KL
authors.lastname: Chua
authors.forename: Yulin
authors.initials: Y
authors.lastname: Lam
mesh_terms: 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
chemical_list: 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