Coding Recognition of the Dose-Effect Interdependence of Small Biomolecules Encrypted on Paired Chromatographic-Based Microassay Arrays

Abstract

The discovery of new small molecular entities in diverse compounds suffers from the lack of a correlation recognition method between bioactivity and molecular characteristics such as DNA base pairing recognition in biomacromolecules. Here, by mapping a sample's 2D-HPTLC fingerprint into microplates with a grid size approximated to that of the chromatographic spots to create paired chromatographic-based microassay arrays, on which the microarray-based differentially expressed chromatographic spots are allowed to develop and assemble into a self-consistent array distribution gradient of multi-attributes of each chromatographic component's own, we propose a screening strategy to self-recognize small biomolecules. Specifically, on the paired chromatographic-based microassay arrays with the chromatographic matrix removed and the chromatographic distribution consistent, bioassays and bioguided LC-ESI-MS tracing are performed naturally, the expressed array distribution gradients of the bioactivity strength vs. the digital-specific quasimolecular ion intensity derived from the same chromatographic component are auto-collimated, and generated a pair of dose-effect interdependent 2D codes encrypted by the chromatographic fingerprint characteristics. Therefore, the recognition of molecules attributed to bioactivity in diverse compounds is transformed into a constraint satisfaction problem, which is addressed through examining the dose-effect interdependence of the 2D code pair by array matching algorithm. This approach represents the paradigm shift in small molecule drug screening from bioassay traversing molecular diversity library item-by-item to self-correlation recognition of each compound's own multiple attributes through its characteristic chromatographic behavior. This research strategy was successfully applied to galangal, and practiced the high-throughput digital preliminary screening of small biomolecules in a natural product.