The cover illustrates the issue topic «Merging Allosteric and Active Site Binding Motifs: De novo Generation of Target Selectivity and Potency via Natural-Product-Derived Fragments»
The synergy of natural-product-derived fragments with structure-based design has been validated as a powerful technique for the efficient de novo discovery of potent and selective lead molecules for modulating therapeutically relevant targets. The front cover picture shows the structural and functional transformation of an RNA nucleobase into aprotease inhibitor employing matrix metalloproteinase 13 (MMP-13) as the protein template.The natural-product-derived fragment uracil has been utilized as a molecular seed for a genuine de novo structure-based approach to highly selective, potent and ligandefficient MMP-13 inhibitors by targeting allosteric and active site binding motifs at the same time. For further details, see the Communication by Rainer Riedl et al. on p. 451 ff.
Sarah Schmitz, SCS