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Updated: Jun 2, 2026

High-Density DNA and RNA microarrays - Photolithographic Synthesis, Hybridization and Preparation of Large Nucleic Acid Libraries
Published on: August 12, 2019
Application of a sparse matrix design strategy to the synthesis of dos libraries
Lakshmi B Akella1, Lisa A Marcaurelle
1Chemical Biology Platform, The Broad Institute of Harvard and MIT, Cambridge Center, Massachusetts 02142, United States.
Abstract:
We have implemented an interactive and practical sparse matrix design strategy for the synthesis of DOS libraries, which facilitates the selection of diverse library members within a user-defined range of physicochemical properties while still maintaining synthetic efficiency. The utility of this approach is illustrated with the synthesis of an 8000-membered library of stereochemically diverse medium-sized rings accessible via a build/couple/pair DOS strategy. Diverse library members were selected from a virtual library by applying the maximum dissimilarity method, while the selection of similar analogs around each diverse product was ensured by picking near neighbors algorithmically based on fingerprint comparison. Adjustable filters on compound properties, which can be tailored to suit the needs of the target biology, facilitated subset selection from the synthetically accessible compounds.
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