Abstract
Over the past decades, peptide-based drugs have gained increasing interest in a wide range of treatment applications, primarily becauseof high potency and selectivity, as well as good efficacy, tolerability, and safety often achieved with peptides. Attempts to target postsynaptic density protein of 95 (PSD-95) PSD-95/Discs large/Zonula occludens-1 (PDZ) domains, which mediate the formation of a ternary complex with the N-methyl-D-aspartate (NMDA) receptor and neuronal nitric oxide synthase (nNOS) responsible for excitotoxicity in ischemic stroke, by high-affinity small molecules have failed in the past. In this chapter, we focus on the discovery of peptide-based drugs targeting PSD-95, using AVLX-144 as an example, from the synthesis, over binding assays to its target, to further in vitro experiments based on the development of AVLX-144, a potential stroke treatment, which is planned to enter clinical trials in 2020.
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