A new series of synthetic protein transduction domain mimics (PTDMs) was designed based on key parameters of Pep-1 and TAT. These novel PTDMs were significantly more active than either Pep-1 or TAT alone. Importantly, they form non-covalent complexes with their protein-based cargo enabling more rapid discovery of intracellular protein delivery function. To better understand the importance of guanidine and phenyl groups segregation along the backbone both membrane interactions and cellular internalization studies were conducted. The results showed that functional group segregation impacts activity. Their ability to deliver active peptides, proteins, and antibodies into primary T-cells was exploited. More recently, insight on PTDM-cargo binding has been developed by combining several techniques. This study gives new design guidelines for the development of PTDMs.<br/>

Non-covalent protein complexes for intracellular delivery of functional cargo

256th National Meeting (2018)

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