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Antimicrobial Agents and Chemotherapy, June 1998, p. 1447-1453, Vol. 42, No. 6
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Screening for Novel Antimicrobials from Encoded Combinatorial Libraries by Using a Two-Dimensional Agar Format

Joy L. Silen, Amy T. Lu, Dennis W. Solas, Medini A. Gore, Derek Maclean, Nikil H. Shah, Jill M. Coffin, Naseema S. Bhinderwala, Yongwen Wang, Ken T. Tsutsui, Gary C. Look,dagger David A. Campbell, Ron L. Hale, Marc Navre, and Camille R. DeLuca-Flaherty*

Affymax Research Institute, Santa Clara, California 95051

Received 10 September 1997/Returned for modification 18 December 1997/Accepted 1 April 1998

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.

* Corresponding author. Mailing address: Biochemistry Department, Affymax Research Institute, 3410 Central Expressway, Santa Clara, CA 95051. Phone: (408) 522-5861. Fax: (408) 481-0522. E-mail: camille_deluca-flaherty{at}affymax.com.

dagger Present address: MetaXen, Inc., Palo Alto, CA 94304.

Antimicrobial Agents and Chemotherapy, June 1998, p. 1447-1453, Vol. 42, No. 6
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.




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