Limiting Assumptions in the Design of Peptidomimetics.
Preclinical Research Limiting the flexibility of organic compounds to enhance their affinity and selectivity for targeting a macromolecule involved in molecular recognition has become a well-developed paradigm in medicinal chemistry. While the role of reverse-turn motifs as peptidomimetics has received the most attention, β-sheets and helices are also important motifs for protein/protein interactions. The more complicated problem of mimicking the interacting surface of noncontiguous epitopes will not be considered in this review. This limited overview focuses on efforts to use amino acid synthons as secondary-structure mimetics as well as providing examples of peptidomimetic design focused on nonpeptide synthetic chemistry in contrast. In particular, the rationale of optimal design criteria for mimicry and the many naïve violations of those criteria made in its pursuit are emphasized. Drug Dev Res 78 : 245-267, 2017. © 2017 Wiley Periodicals, Inc.
['Marshall|Garland R|GR|', 'Ballante|Flavio|F|']
D015195:Drug Design D006801:Humans D008958:Models, Molecular D057786:Peptidomimetics D011485:Protein Binding D013329:Structure-Activity Relationship
beta-sheet mimetics helix mimetics reverse-turn mimetics semi-rigid analogs