Supramolecular Multiplexes from Collagen Mimetic Peptide-PNA(GGG)3 Conjugates and C-rich DNA: pH-induced reversible switching from triplex-duplex to triplex-i-motif

• Published in: Biomaterials science
• Main Authors: More, Shahaji Hanumantrao, Schmutz, Marc, Jierry, Loïc, Ganesh, Krishna
• Format: Journal Article
• Language: English
• Published: 14.11.2024
• ISSN: 2047-4830; 2047-4849; 2047-4849
• DOI: 10.1039/D4BM00955J

Peptides are well known to form nanoparticles while DNA duplexes, triplexes and tetraplexes form rigid nanostructures. Covalent conjugation of peptides to DNA/RNA produces hybrid self-assembling features and may lead to interesting nano assemblies distinct from that of individual components. Herein, we report a collagen mimetic peptide incorporating lysine in backbone and its alkylamino side chains are radially conjugated with G-rich PNA [Collagen-(PNA-GGG)3]. In presence of complementary C-rich DNA (dCCCTTTCCC) at neutral pH the collagen mimetic triplexes are interconnected by PNA-GGG:DNA-CCC duplexes, leading to larger assemblies of nanostructures. Upon decreasing the pH to 4.5, the dissociation of triplex-duplex assembly releases the protonated C-rich DNA which immediately folds into i-motif. Raising the pH to neutral 7.2, the i-motif unfolds into linear DNA that reforms the PNA-GGG:DNA-CCC duplex interconnecting the collagen triplexes. The pH-induced switching of assembly and disassembly is reversible over a few cycles. The hybrid collagen-(PNAGGG)3:DNA-C3T3C3 triplex-duplex and the individual components of the assembly including i-motif have been characterized by UV and CD melting, fluorescence, TEM and gel electrophoresis. The pH induced reversible switching was established by changes in CD and fluorescence properties. Peptide-DNA conjugates are finding enormous applications in both biology and material science ranging from therapeutics and drug delivery to diagnostics and molecular switches The prototype ensemble of triplex peptide-PNA conjugate and its duplex with DNA described here has the potential for elaboration into rationally designed systems by varying the PNA/DNA sequences to trap functional ligands/drugs for release in pH-controlled environments