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- W4297129306 abstract "AbstractHistorically, peptide drug discovery has been very successful in the development of receptor-targeted medicines such as related to insulin and glucagon-like peptide 1 agonists as well as many other examples with respect to many receptors and other extracellular targets. In recent years, there has been significant progress to advance new peptide modalities focused especially on macrocyclic design and leveraging lead molecules from biological and/or chemical diversity approaches, including mRNA-display libraries, phage-display libraries, DNA-encoded synthetic libraries, and one-bead-one-compound synthetic libraries. Such work builds upon existing peptidomimetic and peptide analog optimization strategies involving a native cognate peptide (or protein fragment) and iterative structure-based design. Likewise, there has been incredible progress in structural biology and computational modeling that is contributing to peptide drug modalities, including linear and macrocyclic peptides as well as peptidomimetic analogs thereof. Collectively, this armamentarium of peptide modalities has contributed to the acceleration of breakthrough preclinical molecules. A greater understanding of drug-like properties to tackle an increasing number of intracellular targets (e.g., enzymes and protein–protein interactions) as well as deeper insights related to cell uptake mechanisms, including passive transport and both cationic and lipophilic partitioning models, is being achieved. This chapter exemplifies a few specific cases of intracellular targets and varying peptide drug modalities which illustrate success toward a new wave of novel peptide therapeutics.KeywordsCell-penetrating peptidesMacrocyclic peptidesPeptidomimeticsIntracellular targetsProteaseProteasomePhosphataseFarnesyl transferaseGTPaseSrc SH2XIAPMCL-1HIF-1αNEMOCFTRMDM2MDM4Proteinprotein interactions" @default.
- W4297129306 created "2022-09-27" @default.
- W4297129306 creator A5082655309 @default.
- W4297129306 date "2022-01-01" @default.
- W4297129306 modified "2023-09-30" @default.
- W4297129306 title "Emerging Peptide Drug Modalities for Intracellular Target Space" @default.
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- W4297129306 doi "https://doi.org/10.1007/978-3-031-04544-8_8" @default.
- W4297129306 hasPublicationYear "2022" @default.
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