This work presents the application of spiroligomers as inhibitors of protein-protein interactions. After the discovery of an acyl-transfer coupling reaction by Dr. Zachary Brown, a previous graduate student of Schafmeister group, the synthesis of highly functionalized spiroligomers that mimic the helical domain of p53 was undertaken before each molecule was tested for binding to HDM2, a natural binding partner of p53. A library of molecules was synthesized on solid support that altered the stereochemistry along the spiroligomer as well as the presented functional groups. It was determined that spiroligomers enter human liver cancer cells through passive diffusion and induces a biological response in both a dose- and time-dependent manner. The synthesis of additional spiroligomer analogues achieved low micromolar to high nanomolar range activity during screening in direct and competitive binding assays. In parallel to the project above, a series of spiroligomers that mimic the side chains of the leucine zipper region of Max were synthesized in an effort to disrupt the interaction of the protein with c-Myc. The series of compounds contained various stereocenter combinations and different functional groups as before but were made in solution before testing for inhibition. Initial binding assays resulted in low micromolar activity, however, secondary assays (ELISA and cellular assays) did not confirm the inhibitory effect of spiroligomers on the c-Myc/Max heterodimer. In summary, this work illustrates that spiroligomers are capable mimics of helical peptides and can induce a biological response. / Chemistry