3019-16-7Relevant academic research and scientific papers
Trisubstituted 1,3,5-Triazines: The First Ligands of the sY12-Binding Pocket on Chemokine CXCL12
Fenske, Tyler G.,Getschman, Anthony E.,Smith, Brian C.,Sprague, Daniel J.,Volkman, Brian F.
, p. 1773 - 1782 (2021/11/16)
CXCL12, a CXC-type chemokine, binds its receptor CXCR4, and the resulting signaling cascade is essential during development and subsequently in immune function. Pathologically, the CXCL12-CXCR4 signaling axis is involved in many cancers and inflammatory diseases and thus has sparked continued interest in the development of therapeutics. Small molecules targeting CXCR4 have had mixed results in clinical trials. Alternatively, small molecules targeting the chemokine instead of the receptor provide a largely unexplored space for therapeutic development. Here we report that trisubstituted 1,3,5-triazines are competent ligands for the sY12-binding pocket of CXCL12. The initial hit was optimized to be more synthetically tractable. Fifty unique triazines were synthesized, and the structure-activity relationship was probed. Using computational modeling, we suggest key structural interactions that are responsible for ligand-chemokine binding. The lipophilic ligand efficiency was improved, resulting in more soluble, drug-like molecules with chemical handles for future development and structural studies.
Triazine-Based Sequence-Defined Polymers with Side-Chain Diversity and Backbone-Backbone Interaction Motifs
Grate, Jay W.,Mo, Kai-For,Daily, Michael D.
supporting information, p. 3925 - 3930 (2016/03/19)
Sequence control in polymers, well-known in nature, encodes structure and functionality. Here we introduce a new architecture, based on the nucleophilic aromatic substitution chemistry of cyanuric chloride, that creates a new class of sequence-defined polymers dubbed TZPs. Proof of concept is demonstrated with two synthesized hexamers, having neutral and ionizable side chains. Molecular dynamics simulations show backbone-backbone interactions, including H-bonding motifs and pi-pi interactions. This architecture is arguably biomimetic while differing from sequence-defined polymers having peptide bonds. The synthetic methodology supports the structural diversity of side chains known in peptides, as well as backbone-backbone hydrogen-bonding motifs, and will thus enable new macromolecules and materials with useful functions.
