Parallel synthesis and splicing redirection activity of cell-penetrating peptide conjugate libraries of a PNA cargo

• Published in: Organic & biomolecular chemistry Vol. 11; no. 43; p. 7621
• Main Authors: Deuss, Peter J, Arzumanov, Andrey A, Williams, Donna L, Gait, Michael J
• Format: Journal Article
• Language: English
• Published: England 21-11-2013
• Subjects: Cell-Penetrating Peptides - chemical synthesis; Cell-Penetrating Peptides - chemistry; Cell-Penetrating Peptides - metabolism; Chromatography, High Pressure Liquid; HeLa Cells; Humans; Molecular Conformation; Peptide Library; Peptide Nucleic Acids - chemistry; Peptide Nucleic Acids - metabolism; RNA Splicing - genetics; RNA, Messenger - genetics; RNA, Messenger - metabolism
• ISSN: 1477-0539
• DOI: 10.1039/c3ob41659c

A novel method for the parallel synthesis of peptide-biocargo conjugates was developed that utilizes affinity purification for fast isolation of the conjugates in order to avoid time consuming HPLC purification. The methodology was applied to create two libraries of cell-penetrating peptide (CPP)-PNA705 conjugates from parallel-synthesized peptide libraries. The conjugates were tested for their ability to induce splicing redirection in HeLa pLuc705 cells. The results demonstrate how the novel methodology can be applied for screening purposes in order to find suitable CPP-biocargo combinations and further optimization of CPPs.