Tunable DNA Cleavage by Intercalating Peptidoconjugates

Abstract

The properties of a novel family of peptide-based DNA-cleavage agents are described. Examination of the DNA-cleavage activities of a systematic series of peptide-intercalator conjugates revealed trends that show a strong dependence on peptide sequence. Conjugates differing by a single residue displayed reactivities that varied over a wide range. The cleavage activity was modulated by the electrostatic or steric qualities of individual amino acids. Isomeric conjugates that differed in the position of the tether also exhibited different reactivities. The mechanism of DNA cleavage for these compounds was also probed and was determined to involve hydrogen-atom abstraction from the DNA backbone. Previous studies of these compounds indicated that amino acid peroxides were the active agents in the cleavage reaction; in this report, the chemistry underlying the reaction is characterized. The results reported provide insight into how peptide sequences can be manipulated to produce biomimetic compounds.

Transport of Molecular Cargo by Interaction with Virus‐Like Particle RNA

“…Intercalating dyes like thiazole orange are commonly used to stain nucleic acids or to bring functional components to nucleic acids for the purposes of labeling or cleavage. [40][41][42][43][44] Here we combine this property with two natural features of virus-like particles derived from the Leviviridae class of RNA bacteriophages:( 1) the substantial amounts of RNAe ntrained by these particles during normal recombinant expression and self-assembly and (2) the pores that exist at the six-fold symmetry axes of the icosahedral capsid shell. By attaching thiazole orange to molecules that can diffuse or thread through the capsid, we created structures that noncovalently anchor in the packaged RNA, making it easy to both load the nanoparticles with molecular cargo and to monitor their encapsidation and release.…”

Real time RNA transcription monitoring by Thiazole Orange (TO)-conjugated Peptide Nucleic Acid (PNA) probes: norovirus detection

“…LightUp_PNA was obtained by conjugating the N-terminal PNA sequence with 6-TO exanoic acid. 59 This reaction was performed by using the DIC/DhBTOH coupling protocol and with an extensive coupling time, since the reaction is slow on account of the high steric hindrance.…”

Photoinduced short-range electron transfer in DNA with fluorescent DNA bases: lessons from ethidium and thiazole orange as charge donors

“…For this purpose, it is crucial to covalently link thiazole orange to oligonucleotides. It was tethered to internucleotidic 79 or terminal 80,81 positions of oligonucleotides, to DNA-binding peptides 82,83 and to PNA. [84][85][86] Similar to ethidium, the thiazole orange chromophore exhibits an oxidation potential of E(To + /To 2+ ) = 1.4 V, 87 that together with E 00 = 2.4 V is not sufficient for the photoreduction of any of the DNA bases in order to initiate an electron transfer.…”