A Comprehensive Review on Current Advances in Peptide Drug Development and Design

By Andy Chi-Lung Lee, J. Harris, Kum Khanna, Ji-Hong Hong. International Journal of Molecular Sciences, 2019

564 citations recorded by the source corpus.

Protein–protein interactions (PPIs) execute many fundamental cellular functions and have served as prime drug targets over the last two decades. Interfering intracellular PPIs with small molecules has been extremely difficult for larger or flat binding sites, as antibodies cannot cross the cell membrane to reach such target sites. In recent years, peptides smaller size and balance of conformational rigidity and flexibility have made them promising candidates for targeting challenging binding interfaces with satisfactory binding affinity and specificity. Deciphering and characterizing peptide–protein recognition mechanisms is thus central for the invention of peptide-based strategies to interfere with endogenous protein interactions, or improvement of the binding affinity and specificity of existing approaches. Importantly, a variety of computation-aided rational designs for peptide therapeutics have been developed, which aim to deliver comprehensive docking for peptide–protein interaction interfaces. Over 60 peptides have been approved and administrated globally in clinics. Despite this, advances in various docking models are only on the merge of making their contribution to peptide drug development. In this review, we provide (i) a holistic overview of peptide drug development and the fundamental technologies utilized to date, and (ii) an updated review on key developments of computational modeling of peptide–protein interactions (PepPIs) with an aim to assist experimental biologists exploit suitable docking methods to advance peptide interfering strategies against PPIs.

Subfields: Molecular Biology, Radiology, Nuclear Medicine and Imaging

View Paper: https://www.semanticscholar.org/paper/e28bf03727d51b23c5ccf54b353e50727567e118

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In Radiology, Nuclear Medicine and Imaging

Citations in the corpus

Improving peptide-protein docking with AlphaFold-Multimer using forced sampling (2021, background): “Up to 40% of protein-protein interactions are considered peptide-protein interactions, with many of these responsible for vital functions such as cell life-cycle regulation (Lee et al., 2019).”
Harnessing protein folding neural networks for peptide–protein docking (2021, background): “They also serve as a starting point for the design of strong and stable peptidomimetics (12,13).”
Recent advances in Alzheimer’s disease: mechanisms, clinical trials and new drug development strategies (2024, background): “Although large and ﬂ at PPI interfaces may be more conducive to peptide and protein drug targeting, 75,583,584 small molecule inhibitors also play a role in some AD-related PPIs due to their unique advantages.”