One way to overcome the complexity of protein folding is to explore template-based assemblies. We have explored peptide-oligonucleotide conjugates (POCs) for <i>de novo </i>protein design using orthogonal self-assembly principles. For the initial proof-of-concept study we relied on a sequence derived from CoilVaLd32 which represents an ubiquitous protein motif that exists in 5-10% of all protein sequences. We herein report an efficient and high-yielding preparation of POCs by copper-free alkyne-azide cycloaddition reactions, and we show that ON triple helix-formation can be used to organize peptide strands leading to the formation of highly stable three-helix bundle protein-mimics. Next generation designs and structures are revealed together with alternative designs based on oligonucleotide conjugates of insulin.

Design and assembly of artificial proteins using nucleic acid hybridization

253rd National Meeting (2017)

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