Current Topics in Medicinal Chemistry - Volume 18, Issue 7, 2018

Backbone-cyclized peptides and peptidomimetics integrate the biological activity and pharmacological features necessary for successful research tools and therapeutics. In general, these structures demonstrate improved maintenance of bioactive conformation, stability and cell permeability compared to their linear counterparts, while maintaining support for a variety of side chain chemistries. We explain how backbone cycliz Read More

Protein-protein Interactions (PPIs) are particularly important for controlling both physiologic and pathologic biological processes but are difficult to target due to their large and/or shallow interaction surfaces unsuitable for small molecules. Linear peptides found in nature interact with some PPIs, and protein active regions can be used to design synthetic peptide compounds for inhibition of PPIs. However, linear peptides are limited Read More

The concept of a peptidomimetic was coined about forty years ago. Since then, enormous effort and interest have been devoted to mimic the properties of peptides with small molecules or pseudopeptides. The present report aims to review different approaches described in the past to succeed in this goal. Basically, there are two different approaches to design peptidomimetics: a medicinal chemistry approach, where p Read More

The long-lasting impetus to design novel modes of macrocyclization, and their implementation into a wide range of bioactive peptides, originates from their contributions to the restriction of conformational space and the stabilization of preferential bioactive conformations that support higher efficacy and binding affinity to cognate macromolecular targets, improved specificity and lowering susceptibility to enzymatic degradati Read More

Anomalous protein-protein interactions (PPIs) have been correlated to a variety of disease states, such as cancer, infectious disease, neurological disorders, diabetes, endocrine disorders and cardiovascular disease. Stapled peptides are an emerging intervention for these PPIs due to their improved structural rigidity and pharmacokinetic properties relative to unstapled peptides. This review details the most recent advances Read More

Cyclic peptide scaffolds are key components of signal transduction pathways in both prokaryotic and eukaryotic organisms since they act as chemical messengers that activate or inhibit specific cognate receptors. In prokaryotic organisms these peptides are utilized in non-essential pathways, such as quorum sensing, that are responsible for virulence and pathogenicity. In the more evolved eukaryotic systems, cyclic Read More