The advent of monoclonal antibodies (mAbs) was a breakthrough in the treatment of cancer, including the use of Rituximab for the treatment of non-Hodgkin’s lymphoma and chronic lymphocytic lymphoma, as well as the use of Trastuzumab for the treatment of HER2+ breast cancer. mAbs can exert their therapeutic effect via several different pathways, one of which is through the induction of complement-dependent cytolysis (CDC) that leads to the formation of membrane attack complex (MAC) pores on the tumour cell surface which result in lysis and death. However, many cancer cells overexpress CD59, a small GPI‑anchored protein, that restricts the formation of MAC, thereby inhibiting induction of CDC and playing a role in the development of resistance against mAbs therapy. Therefore, there is a clinical need to develop potent inhibitors of CD59 as adjuvants to mAbs in order to restore the CDC effect on cancer cells. A diverse library of monocyclic thioether peptides was screened against CD59 using mRNA display technology, which lead to the identification of six cyclic peptides which are nanomolar affinity ligands for CD59. This project aims to optimise the initial hits through determination of the structure-activity relationship (SAR) for the peptide hits, two of which are presented here. Alanine scanning derivatives of both peptides were synthesised using Fmoc SPPS. Subsequently, their affinities for CD59 were assessed using SPR, enabling identification of key residues in the peptide sequences which are essential for binding as well as residues suitable for modification with a fluorophore or bioorthogonal handle. Based on the SAR studies, chemical tools for CD59 have been developed this include: Trastuzumab-peptide conjugate, Photocrosslinking peptide, dimer peptide, fluorescent peptide, and tailed peptide. The results presented here demonstrate progress toward the development of potent, cell-active peptide-based inhibitors of CD59 which may serve as adjuvants to mAbs in cancer therapy.