Author: Lombardi Research Lab

Over the past two decades, peptide drug discovery has experienced a remarkable renaissance, with organic chemistry and biotechnology emerging as pivotal tools for developing peptidomimetics that exhibit improved stability, specificity, and bioavailability compared to conventional peptides. This review systematically examines methodologies for modifying peptide backbones to achieve targeted properties, highlighting recent advances facilitated by modern…

Read More “NEW PAPER: Advances in Peptidomimetics for Next-Generation Therapeutics: Strategies, Modifications, and Applications” »

Jiaxu Li designed the nice cover for our article “Advancements in Loop Cyclization Approaches for Enhanced Peptide Therapeutics for Targeting Protein-Protein Interactions,” which was published in The Journal of Organic Chemistry in collaboration with Robin Shattock and Luke Granger.

De novo protein design has advanced such that many peptide assemblies and protein structures can be generated predictably and quickly. The drive now is to bring functions to these structures, for example, small-molecule binding and catalysis. The formidable challenge of binding and orienting multiple small molecules to direct chemistry is particularly important for paving the way to new functionalities.

This study focuses on mimicking peptide loops as a strategy for PPI inhibition, utilizing synthetic peptide loops for replicating critical binding regions. This work explores turn-inducing elements and highlights the importance of proline in promoting favorable conformations for lactamization, yielding high-purity cyclic peptides.