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.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Mann, Meagan K.

Contributors dc:contributor

• Katzenellenbogen, John A.

• Chemistry, Biochemistry

Language dc:language

eng

Identifier

(MiAaPQ)AAI3337858

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/84317