Supramolecular chemistry using synthetic cavitands provides enormous untapped potential for reversibly modulating, modifying, and controlling protein conformation and oligomerization states. The melding of cavitand-mediated molecular recognition with peptide-based recognition offers new avenues for supramolecular control of biologically important processes, as well as construction of synthetic miniproteins and the presentation of structured molecular recognition motifs. CB[n]s are promising candidates for these applications due to their high affinity and selectivity and lack of cytotoxicity.<br/>Recently we discovered new short peptide sequences that dimerize in an antiparallel fashion <i>via</i> double supramolecular complexation with cucurbit[8]uril (CB[8]) to form 2+2 complexes. Our short term goal to verify the oligomerization state and investigate the structure and thermodynamic behavior of these peptide-CB[8] complexes in detail is under way. Further, we are carrying out studies to uncover the critical determinants of molecular recognition/dimer formation, to optimize binding affinities, and to develop orthogonal dimerization domains. Our long-term goal is to develop them into a versatile assembly motif with potential applications including as platforms for antibody-like molecular recognition, supramolecular catalysis, and modular dimerization domains for protein assembly.

Cucubit[8]-uril mediated peptide dimerization

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.