Article
Chemistry, Multidisciplinary
Nitin A. Patil, Varsha J. Thombare, Rong Li, Xiaoji He, Jing Lu, Heidi H. Yu, Hasini Wickremasinghe, Kavya Pamulapati, Mohammad A. K. Azad, Tony Velkov, Kade D. Roberts, Jian Li
Summary: Peptide-Peptide Nucleic Acid (PNA) conjugates have shown potential in developing novel antisense antimicrobials. The efficiency of Cys-CINA conjugation was investigated for synthesizing peptide-PNA conjugates, which demonstrated improved antimicrobial activity against multidrug-resistant Gram-negative bacteria.
FRONTIERS IN CHEMISTRY
(2022)
Article
Nanoscience & Nanotechnology
Huiying Xu, Chong Liao, Shifu Liang, Bang-Ce Ye
Summary: Exosomes are natural delivery vehicles with features like low immunogenicity, excellent biocompatibility, and migration capability. This study developed a novel peptide-equipped exosomes platform that can improve cellular uptake efficiency and deliver nucleic acids effectively, showing potential for personalized cancer medicine.
ACS APPLIED MATERIALS & INTERFACES
(2021)
Article
Pharmacology & Pharmacy
Mohadeseh Dastpeyman, Ramin Sharifi, Azin Amin, John A. Karas, Brittany Cuic, Yijun Pan, Joseph A. Nicolazzo, Bradley J. Turner, Fazel Shabanpoor
Summary: This study demonstrates that integrating endosomal escape domains with CPPs can improve the intracellular delivery efficiency of ASOs, and enhance the efficiency of BBB-permeability and CNS activity of systemically administered ASOs.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2021)
Article
Chemistry, Analytical
Toshitsugu Fujita, Shoko Nagata, Hodaka Fujii
Summary: Blocking PCR is a method to selectively inhibit the amplification of wild-type DNA while amplifying mutated DNA by using a nucleotide sequence complementary to a blocker. Our study demonstrates that an oligoribonucleotide (ORN) can effectively suppress the extension of target DNA by Taq DNA polymerases. This method has been successfully applied for real-time ORNi-PCR and one-step real-time reverse transcriptionORNi-PCR to detect single-nucleotide mutations in DNA and RNA in a sequence-specific manner, providing technical insights for further improvement of blocking PCR.
ANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Chengxi Li, Alex J. Callahan, Kruttika S. Phadke, Bryan Bellaire, Charlotte E. Farquhar, Genwei Zhang, Carly K. Schissel, Alexander J. Mijalis, Nina Hartrampf, Andrei Loas, David E. Verhoeven, Bradley L. Pentelute
Summary: This study reports an efficient technology that utilizes a fully automated fast-flow instrument to manufacture cell-penetrating peptide-conjugated peptide nucleic acids (PPNAs), which improves cellular uptake. The synthesized PPNAs showed improved activity in splice-correction and antiviral assays. This technology has the potential to be used for further investigation of PPNA candidates as antiviral agents.
ACS CENTRAL SCIENCE
(2022)
Article
Chemistry, Multidisciplinary
Carly K. Schissel, Somesh Mohapatra, Justin M. Wolfe, Colin M. Fadzen, Kamela Bellovoda, Chia-Ling Wu, Jenna A. Wood, Annika B. Malmberg, Andrei Loas, Rafael Gomez-Bombarelli, Bradley L. Pentelute
Summary: The study demonstrates that deep learning can decipher design principles to generate highly active biomolecules, such as Mach proteins, which are capable of delivering antisense cargo efficiently without toxicity in mice. This approach combines high-throughput experimentation with a deep-learning method inspired by directed evolution, representing molecular structures as topological fingerprints.
Review
Cell Biology
Umme Sabrina Haque, Toshifumi Yokota
Summary: Antisense oligonucleotide-based therapeutics have great potential for treating human disorders, while the efficient delivery to target cells remains a challenge. Cell-penetrating peptides (CPPs), especially DG9 peptide, show promise in enhancing the cellular uptake and intracellular delivery of oligonucleotide-based drugs. Several studies have demonstrated the potential of DG9-conjugated PMOs in treating DMD and SMA in animal models.
Article
Biochemistry & Molecular Biology
Greta Linden, Harshavardhan Janga, Matthias Franz, Andrea Nist, Thorsten Stiewe, Bernd Schmeck, Olalla Vazquez, Leon N. Schulte
Summary: This study successfully utilized cell penetrating peptide chemistry to enable the loss-of-function phenotyping of regulatory RNAs in primary human blood-derived cells. The results showed that PNA-R8 was effective at a lower concentration than previously believed and highlighted the important role of microRNA-155 in fine control of human phagocyte immunity.
Article
Chemistry, Multidisciplinary
Pramod M. Sabale, Mateusz Imiolek, Pierre Raia, Sofia Barluenga, Nicolas Winssinger
Summary: This study presents a hybrid strategy based on short PNA-peptide conjugates to constrain peptide fragments into an enforced alpha-helical conformation. Through native chemical ligation, a mixture of peptide fragments can be combinatorially ligated and used directly in affinity selection against a target of interest, as demonstrated with a focused library targeting the p-53/MDM2 interaction.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Engineering, Biomedical
Hui Shao, Jin Zhou, Xiaoqian Lin, Yue Zhou, Yumeng Xue, Weili Hong, Xubo Lin, Xiaoling Jia, Yubo Fan
Summary: Developing new antimicrobial agents to combat drug-resistant pathogens and biofilms is an urgent task. Cationic antimicrobial peptides (AMPs) have potential due to their unique membrane rupture mechanism, but their high toxicity and low stability limit their application. In this study, a biomimetic strategy was used to construct cationic peptide-conjugated liposomes, inspired by cell-penetrating peptides (CPPs), to enhance antibacterial efficacy and biosafety. Computational simulation and experimental investigations identified the optimal peptide-conjugated liposomes, which showed enhanced antibacterial efficacy without compromising cytotoxicity. This bio-inspired design could contribute to the development of next-generation antimicrobials.
Article
Biochemical Research Methods
Martina Traykovska, Katya B. Popova, Robert Penchovsky
Summary: This study developed novel chimeric antisense oligonucleotides targeting glmS riboswitch and nagA mRNA to inhibit the growth of Staphylococcus aureus by blocking bacterial metabolic pathways. The specific targeting of glmS riboswitch was found to be sufficient to inhibit the bacterial growth, making it a promising target for antibacterial drug development using antisense oligonucleotides.
ACS SYNTHETIC BIOLOGY
(2021)
Article
Microbiology
Corina Abt, Lisa Marie Gerlach, Jana Bull, Anette Jacob, Bernd Kreikemeyer, Nadja Patenge
Summary: Research found that hydrophobic counterion PyB can facilitate the translocation of CPP-antisense PNAs across bacterial membrane, thus enhancing its antimicrobial activity, but PyB does not significantly affect the antimicrobial activity of CPP-conjugated PNAs in Streptococcus pneumoniae.
Article
Chemistry, Multidisciplinary
Luis Moreira, Nuno M. Guimaraes, Sara Pereira, Rita S. Santos, Joana A. Loureiro, Rui M. Ferreira, Ceu Figueiredo, Maria C. Pereira, Nuno F. Azevedo
Summary: Liposomes loaded with nucleic acid mimics (NAMs)-modified oligonucleotides (LipoNAMs) were evaluated for delivering antisense oligonucleotides (ASOs) in Escherichia coli. Different surface modifications, such as methoxyPEG coating and conjugation of antibodies, were tested to improve delivery efficiency and selectivity. Antibody coupling to PEGylated liposomes significantly enhanced the delivery of ASOs in E. coli, providing potential alternative routes for the treatment of bacterial infections.
JOURNAL OF CONTROLLED RELEASE
(2023)
Article
Biochemistry & Molecular Biology
Alireza Japoni Nejad, Nader Shahrokhi, Peter E. Nielsen
Summary: In this study, a series of PNA-BPP conjugates targeting CRAB strains were designed and synthesized. These compounds demonstrated potent antimicrobial activity against CRAB, exhibiting complete growth inhibition at 1-2x MIC and sensitivity in 12 isolates. Additionally, the conjugates showed no bacterial membrane disruption activity and no cellular toxicity in HepG2 cells, indicating potential as precision designer antibiotics for specific treatment of CRAB infections.
Article
Biotechnology & Applied Microbiology
Vinay G. Joshi, Kantaraja Chindera, Manish Bais, Basavaraj Sajjanar, Ashok K. Tiwari, Satish Kumar
Summary: PNA is a chimeric molecule with advantages over natural antisense nucleic acid molecules, but faces challenges in cellular delivery due to its charge-neutral nature. The proposed novel RATH-2 peptide-based non-covalent PNA delivery mechanism showed promising results in cellular delivery and therapeutic application in antiviral intervention.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2021)
Article
Chemistry, Medicinal
Izabela Siekierska, Maciej Lukaszewicz, Remigiusz Worch, Marzena Jankowska-Anyszka, Karolina Piecyk
Summary: Aryloxy triester phosphoramidate methodology is widely used in prodrug approaches for therapeutic nucleosides. In this study, we applied this methodology to synthesize bioactive 5'-mRNA cap analogues and tested their enzymatic activation, inhibitory properties, and membrane translocation properties.