Synthesis of Non-Steroidal Estrogen Receptor Proteolysis Targeting Chimeric Molecules (Protacs)
To make the PROTAC design more useful, a small molecule E3 ligase peptide mimic is desirable. The HIF-1alpha E3 ligase destruction sequence utilized in the PROTAC design requires a hydroxylated proline residue for recognition by the VCB E3 ligase. The synthesis of a tetrahydrofuran-based hydroxyproline analog was attempted with encouraging results. Upon completion of the synthesis, this analog can be attached to an ER ligand in place of the HIF-1alpha destruction sequence and tested as the first non-peptide based PROTAC.
University of Illinois - Urbana-Champaign
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University of Illinois at Urbana-Champaign