Abstract: Provided herein are oligonucleotides, trimeric peptides, and peptide-oligonucleotide-conjugates. Also provided herein are methods of treating a muscle disease in a subject in need thereof, comprising administering to the subject oligonucleotides, trimeric peptides, and peptide-oligonucleotide-conjugates described herein. A synthetic method provides for the generation of a library of cell-penetrating peptides conjugated to an antisense oligonucleotide, and a machine learning-based generator-predictor-optimizer loop for the generation of novel peptide sequences capable of enhanced delivery of oligonucleotide cargo from the library of conjugates.

Abstract: The disclosure provides platinum(IV) prodrug perfluoroaryl peptide conjugates that can be used to treat cell proliferative disorders, such as those associated with malignant tumor cells. The conjugates can improve the delivery of platinum(IV) prodrugs to glioma cells.