In the contemporary paradigm concerning the emergence of therapy-resistant recurrent cancer, recent studies posit the existence of a limited population of self-renewing malignant progenitors known as cancer stem cells (CSCs). The presence of CSCs explains why tumors often relapse despite clinical remission with initial therapeutic interventions. Consequently, the development of innovative therapeutic modalities specifically tailored to target and eliminate CSCs represents a highly promising strategy for eradicating cancer without the risk of recurrence. In previous research, we successfully developed a synthetic peptoid-based ligand CL-1-19-1 that selectively binds to CSC over non-CSC. However, CL-1-19-1 did not exhibit any significant inhibitory effect on CSC properties. To enhance the CSC-eliminating capabilities of CL-1-19-1, we developed a novel approach by designing a “hunter-killer” peptoid-peptide conjugate. This conjugate combines CL-1-19-1 with a killer peptide sequence (KLAKLAK)2, known for its ability to induce apoptosis by disrupting the outer mitochondrial membrane. We will delve into this conjugate's specific induction of apoptotic cell death in CSCs and explore its therapeutic potential for eradicating CSCs in vivo.

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Jiyong Lee, Sean Butler, Dustin Patterson


Masters in Chemistry

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