Metal-Free DNA Linearized Nuclease Based on PASP–Polyamine Conjugates

Abstract

Genome manipulation controlled by small metal complexes has attracted extensive interest because of their potential application in the fields of molecular biotechnology and drug development. However, their medicinal application is still limited due to the distinct toxicity of the free radicals generated by partial metal complexes based on oxidative cleaving processes. Thus, it is still a challenge for us to use metal free agent to cleave DNA. In this work, we showed that a family of polyamine-grafted PASP (poly(aspartic acid)) conjugates is able to rapidly induce DNA cleavage in the absence of metal ions, and obtain a high-yield linearization product via a hydrolytic path. From the results of detailed control experiments, it was revealed that the formation of polyamine cation/phosphate anion pair and free ungrafted nucleophilic groups would be the key factors to improve DNA linearization. Constructing polyamine conjugates based on short peptide such as polyamine-grafted PASP, as achieved here, could provide an attractive strategy for developing mild and efficient artificial nucleases as well as researching catalytic mechanisms on DNA chemistry.

Complexation behaviors of hyperbranched cationic glycogen derivatives with plasmid DNA revealed by resonance light scattering and circular dichroism spectroscopy

“…Similar diverse effects of cationic polymers on pDNA conformation have been reported previously . In addition, the absence of CD signals over 310–400 nm suggested the absence of minor groove binding between the DMAPA‐Glyp‐2.8 derivative and pDNA .…”

Branched Amphiphilic Cationic Oligopeptides Form Peptiplexes with DNA: A Study of Their Biophysical Properties and Transfection Efficiency

“…As previously reported the branched peptides bis(h 9 :h 5 )-K-K 4 -peptides form capsules in water and act as hollow nano-carriers for small solutes [26][27][28] Delivering of small interfering RNAs (siRNA) into cells is a selective method to degrade messenger RNA (mRNA) and therefore inhibit the expression of a specific protein. siRNA therapeutics has grown rapidly and there are several clinical trials ongoing or planned 47 .…”

Aromatic Modification of Low Molecular Weight PEI for Enhanced Gene Delivery

“…As shown in Figure 2, with the addition of OEI-W10 , the molar ellipticities of DNA at 245 nm and 279 nm were distinctly suppressed from a w / w of 0.6 together with a certain quantity of red shift. We speculate that the signal change might be ascribed to the intercalation of indole rings into the DNA base pairs [16,41]. On the other hand, other polycations just led to a slight red shift but no obvious suppression of molar ellipticity.…”