Discovery, affinity maturation and multimerization of small molecule ligands against human tyrosinase and tyrosinase-related protein 1
Marco Catalano, Gabriele Bassi, Giulia Rotondi, Lyna Khettabi, María G. Dichiara, Patrizia Murer, Jörg Scheuermann, Montserrat Soler‐López, Dario Neri
Abstract
selections with DNA-encoded libraries, we discovered novel ligands capable of binding to both hTYR and hTYRP1. More potent ligands were obtained by multimerizing Thiamidol™ moieties, leading to homotetrameric structures that avidly bound to melanoma cells, as revealed by flow cytometry. These findings suggest that melanoma lesions may, in the future, be targeted not only by monoclonal antibody reagents but also by small organic ligands.
Topics & Concepts
TyrosinaseMelanomaChemistryContext (archaeology)MelaninMolecular biologyDNASmall moleculeBiochemistryEnzymeBiologyCancer researchPaleontologymelanin and skin pigmentationMonoclonal and Polyclonal Antibodies ResearchChemical Synthesis and Analysis