Active site directed inhibitors of replication-specific bacterial DNA polymerases

Bioorganic and Medicinal Chemistry Letters

Volumn 15, Issue 3, 2005, Pages 729-732

  Wright, George E ^a   Brown, Neal C ^a   Xu, Wei Chu ^a   Long, Zheng Yu ^a   Zhi, Chengxin ^a   Gambino, Joseph J ^a   Barnes, Marjorie H ^b   Butler, Michelle M ^b  

^a GLSYNTHESIS INC   (United States)

^b MICROBIOTIX INC   (United States)

Author keywords

Antibacterial; Broad spectrum; Competitive inhibitors; DNA polymerase; Replication

Indexed keywords

DNA DIRECTED DNA POLYMERASE GAMMA; DNA POLYMERASE; DNA POLYMERASE IIIC; DNA POLYMERASE IIIE; GUANINE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; COMPETITIVE INHIBITION; CONTROLLED STUDY; DRUG POTENCY; ENZYME ACTIVE SITE; ENZYME INHIBITION; GRAM NEGATIVE BACTERIUM; GRAM POSITIVE BACTERIUM; NONHUMAN;

BACTERIAL PROTEINS; BINDING SITES; BINDING, COMPETITIVE; DNA POLYMERASE III; DNA REPLICATION; DNA-DIRECTED DNA POLYMERASE; GRAM-NEGATIVE BACTERIA; GRAM-POSITIVE BACTERIA; GUANINE; HUMANS; KINETICS; STRUCTURE-ACTIVITY RELATIONSHIP; URACIL;

BACTERIA (MICROORGANISMS);

EID: 12444330868     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2004.11.016     Document Type: Article

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12. Recombinant pol IIIC and pol IIIE of Bacillus subtilis (B.s.) were prepared according to R. Hammond, M. Barnes, S. Mack, J. Mitchener, and N. Brown Gene 98 1991 29 and Ref. 5, respectively. E. coli (E.c.) pol IIIE was the three subunit core enzyme purchased from Enzyco. The enzymes were assayed with activated calf thymus DNA according to the method described by
13. i values) were obtained directly in a truncated assay lacking the competitor dGTP (Wright, G. E.; Brown, N. C. Biochim. Biophys. Acta 1976, 432, 37), or conventionally by variation of the concentration of dGTP
14. 3, stirred for 0.5 h, and concentrated. Water was added and the suspension was filtered, giving the 4-iodobutyl intermediate (93%). A solution of the 4-iodobutyl intermediate and excess morpholine in MeCN was stirred at rt for 18 h. Concentration and crystallization of the residue from MeOH gave 4j (71%). Yields and properties of all new compounds are in Supporting Information
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