title: Screening for novel antimicrobials from encoded combinatorial libraries by using a two-dimensional agar format.
abstract: A sensitive lawn-based format has been developed to screen bead-tethered combinatorial chemical libraries for antimicrobial activity. This method has been validated with beads linked to penicillin V via a photocleavable chemical linker in several analyses including a spike-and-recover experiment. The lawn-based screen sensitivity was modified to detect antibacterial compounds of modest potency, and a demonstration experiment with a naive combinatorial library of over 46,000 individual triazines was evaluated for antibacterial activity. Numerous hits were identified, and both active and inactive compounds were resynthesized and confirmed in traditional broth assays. This demonstration experiment suggests that novel antimicrobial compounds can be easily identified from very large combinatorial libraries of small, nonpeptidic compounds.
authors.affiliation: Affymax Research Institute, Santa Clara, California 95051, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Silen
authors.forename: A T
authors.initials: AT
authors.lastname: Lu
authors.forename: D W
authors.initials: DW
authors.lastname: Solas
authors.forename: M A
authors.initials: MA
authors.lastname: Gore
authors.forename: D
authors.initials: D
authors.lastname: MacLean
authors.forename: N H
authors.initials: NH
authors.lastname: Shah
authors.forename: J M
authors.initials: JM
authors.lastname: Coffin
authors.forename: N S
authors.initials: NS
authors.lastname: Bhinderwala
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: K T
authors.initials: KT
authors.lastname: Tsutsui
authors.forename: G C
authors.initials: GC
authors.lastname: Look
authors.forename: D A
authors.initials: DA
authors.lastname: Campbell
authors.forename: R L
authors.initials: RL
authors.lastname: Hale
authors.forename: M
authors.initials: M
authors.lastname: Navre
authors.forename: C R
authors.initials: CR
authors.lastname: DeLuca-Flaherty
mesh_terms: D001412:Bacillus subtilis / Q000187:drug effects*; D008826:Microbial Sensitivity Tests / Q000379:methods*; D010782:Photolysis; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D014227:Triazines