title: 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.
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing, 100029, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.forename: Fangfang
authors.initials: F
authors.lastname: Zhao
authors.forename: Yunan
authors.initials: Y
authors.lastname: Huang
authors.forename: Xueyuan
authors.initials: X
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Renzhong
authors.initials: R
authors.lastname: Qiao
authors.forename: Yufen
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D004591:Electrophoresis, Polyacrylamide Gel; D018625:Microscopy, Atomic Force; D010455:Peptides / Q000737:chemistry*; D011073:Polyamines / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D010455:Peptides; D011073:Polyamines; C017645:polyaspartate; D004247:DNA