Principles, implementation, and application of biology-oriented synthesis (BIOS)

Abstract

Biology-oriented synthesis (BIOS) represents an alternative approach for the generation of compound collections for biological applications. In BIOS, biologically relevant and prevalidated scaffold structures, such as core structures of natural products or known drugs, are employed as scaffolds for the generation of compound collections with focused diversity. In this review, we discuss the underlying concept of the BIOS approach, and its practical implementation in library design and synthesis. To highlight its relevance for chemical biology applications, we finally present examples in which compound collections generated under the BIOS principle have been used to elucidate biological questions.

Recent Trends and Observations in the Design of High-Quality Screening Collections

“…This observation is in agreement with the BIOS concept advocated by Waldmann's group, stating that conserved chemical ring systems within natural products provide evolutionary prevalidated starting points for library design [22][23][24][25][26]. Based on such observations, a 'natural product-likeness' score [27] and several 'metabolite-likeness' scores [28][29][30] were recently introduced to prioritize molecules that share similar properties as natural metabolites.…”

“…A similar reasoning is underlying Waldmann's BIOS approach [22][23][24][25][26] that also claims that proteins with structurally highly similar ligand-binding domains are likely to bind similar ligands. A strategy that is even more abstracting from the overall protein structure is the concept of binding site similarity [86][87][88][89][90][91].…”

Advanced Screening to Identify Novel Pesticides

“…HTS technology is very simple and easy to understand, but it has some disadvantages such as the limitation of the combinatorial synthesis of low molecules and the utilization of a known screening system. In order to compensate the shortage of target oriented synthesis (TOS)-guided HTS, the "Diversed-Oriented Synthesis (DOS)" method (Burke and Schreiber 2004 ;Schreiber 2000 ) and the "Biology Oriented Synthesis (BIOS)" were developed (Wilk et al 2010 ) . In contrast to retrosynthetic TOS, DOS is a forward synthetic analysis.…”

Substituted derivatives of indole acetic acid as aldose reductase inhibitors with antioxidant activity: structure-activity relationship

“…Considering the ubiquity of indoles in a wide range of natural products, we believe that the common indole core may represent a natural product scaffold as a starting point for "biologically oriented synthesis" (Wilk et al 2010) of novel biology active agents, as indicated above.…”