1 research outputs found
Synthesis and Incorporation into Cyclic Peptides of Tolan Amino Acids and Their Hydrogenated Congeners: Construction of an Array of A–B-loop Mimetics of the Cε3 Domain of Human IgE
The disruption of the human immunolobulin E–high
affinity
receptor I (IgE–FcεRI) protein–protein interaction
(PPI) is a validated strategy for the development of anti asthma therapeutics.
Here, we describe the synthesis of an array of conformationally constrained
cyclic peptides based on an epitope of the A–B loop within
the Cε3 domain of IgE. The peptides contain various tolan (i.e.,
1,2-biarylethyne) amino acids and their fully and partially hydrogenated
congeners as conformational constraints. Modest antagonist activity
(IC<sub>50</sub> ∼660 μM) is displayed by the peptide
containing a 2,2′-tolan, which is the one predicted by molecular
modeling to best mimic the conformation of the native A–B loop
epitope in IgE