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Publication Abstract from PubMed

Helix mimicry provides probes to perturb protein-protein interactions (PPIs). Helical conformations can be stabilized by joining side chains of non-terminal residues (stapling) or via capping fragments. Nature exclusively uses capping, but synthetic helical mimics are heavily biased towards stapling. This study comprises: (i) creation of a searchable database of unique helical N-caps (ASX motifs, a protein structural motif with two intramolecular hydrogen-bonds between aspartic acid/asparagine and following residues); (ii) testing trends observed in this database using linear peptides comprising only canonical L-amino acids; and, (iii) novel synthetic N-caps for helical interface mimicry. Here we show many natural ASX motifs comprise hydrophobic triangles, validate their effect in linear peptides, and further develop a biomimetic of them, Bicyclic ASX Motif Mimics (BAMMs). BAMMs are powerful helix inducing motifs. They are synthetically accessible, and potentially useful to a broad section of the community studying disruption of PPIs using secondary structure mimics.

Bioinformatics leading to conveniently accessible, helix enforcing, bicyclic ASX motif mimics (BAMMs).,Mi T, Nguyen D, Gao Z, Burgess K Nat Commun. 2024 May 17;15(1):4217. doi: 10.1038/s41467-024-48323-z. PMID:38760359^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.