Protein-protein interactions (PPIs) mediate a number of essential cellular processes and their implication in numerous diseased states - including HIV and cancer - makes them desirable targets for therapeutic intervention. It is however still unclear how to target them, considering their relative lack of defining features. A large proportion of PPIs however involve binding of an α-helix into a hydrophobic cleft on the other protein’s surface and a few key residues located along one helical face have been identified as a recurring and critical pattern for binding. Mimicking the helical core and replicating the spatial arrangement of these residues has therefore become a desirable strategy to abolish such interactions. Building on previous studies from the group, the work described in this thesis aimed to use an N-alkylated oligoamide scaffold to target α-helix mediated PPIs. In particular, the study focused on the assembly and screening of a library of oligobenzamides against two key oncogenic targets (p53/hDM2 and Noxa B/Mcl-1), with a view to setting the basis for a generic approach towards the selective inhibition of α-helix mediated PPIs. The model interactions for this study and their biological context are described in Chapter 1, as well as the different approaches that have emerged to achieve α-helix mimicry. An automated microwave assisted solid phase methodology has been developed which makes use of the Fmoc protection strategy and is reported in Chapter 2. The robustness of this methodology was demonstrated through the assembly of a library of 75 compounds. This library is described in Chapter 3, along with its biophysical assessment and preliminary cell assays. Chapter 4 describes the design and synthesis of oligoureas and their potential as helix mimetics was assessed against the p53/hDM2 PPI.