Natural endogenously occurring peptides exhibit desirable medicinal properties, but are often limited in application by rapid proteolysis and inadequate membrane permeability. However, editing naturally occurring peptide sequences to develop peptidomimetic analogs created a promising class of therapeutics that can augment or inhibit molecular interactions. Here, we discuss a variety of chemical modifications, including l to d isomerization, cyclization, and unnatural amino acid substitution, as well as design strategies, such as attachment to cell-penetrating peptides, which are used to develop peptidomimetics. We also provide examples of approved peptidomimetics and discuss several compounds in clinical trials.
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| http://dx.doi.org/10.1016/j.drudis.2016.11.003 | DOI Listing |
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Article Synopsis
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- Thirteen peptoid analogues were synthesized with varying alkyl side chains to analyze their antibacterial properties, and only one, called Tosyl-Octyl-Peptoid (TOP), showed significant broad-spectrum bactericidal activity.
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