Variation of Tetrahydrofurans in Thyclotides Enhances Oligonucleotide Binding and Cellular Uptake of Peptide Nucleic Acids

被引：5
作者：
Zheng, Hongchao [1 ]
Clausse, Victor [1 ]
Amarasekara, Harsha [1 ]
Mazur, Sharlyn J. [2 ]
Botos, Istvan [3 ]
Appella, Daniel H. [1 ]
机构：
[1] NIDDK, Synthet Bioact Mol Sect, Lab Bioorgan Chem LBC, NIH, Bethesda, MD 20892 USA
[2] NCI, Lab Cell Biol, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA
[3] NIDDK, Lab Mol Biol, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA
来源：
JACS AU | 2023年 / 3卷 / 07期
关键词：
thyclotide; peptide nucleic acids (PNAs); bindingproperties; cell uptake; X-ray crystal structure; backbone modification; miR-21; inhibition; preorganization; ANTISENSE OLIGONUCLEOTIDES; CRYSTAL-STRUCTURE; PNA; DNA; DELIVERY; RECOGNITION; HELIX; THERMODYNAMICS; STABILITY; HYDRATION;
D O I：
10.1021/jacsau.3c00198
中图分类号：
O6 [化学];
学科分类号：
0703 ;
摘要：
Selectiveincorporation of conformational constraintsinto thyclotidescan be used to modulate their binding to complementary oligonucleotides,increase polarity, and optimize uptake into HCT116 cells without assistancefrom moieties known to promote cell uptake. The X-ray structure andbiophysical studies of a thyclotide-DNA duplex reveal thatincorporation of tetrahydrofurans into an aegPNAbackbone promotes a helical conformation that enhances binding tocomplementary DNA and RNA. Selective incorporation of tetrahydrofuransinto the aegPNA backbone allows polarity to be increasedincrementally so that uptake into HCT116 cells can be optimized. Theenhanced binding, polarity, and cellular uptake properties of thyclotideswere used to demonstrate effective inhibition of microRNA-21 in HCT116cells.
引用
收藏
页码：1952 / 1964
页数：13
相关论文
共 50 条
  • [41] Chemical structure requirements and cellular targeting of microRNA-122 by peptide nucleic acids anti-miRs
    Torres, Adrian G.
    Fabani, Martin M.
    Vigorito, Elena
    Williams, Donna
    Al-Obaidi, Naowras
    Wojciechowski, Filip
    Hudson, Robert H. E.
    Seitz, Oliver
    Gait, Michael J.
    NUCLEIC ACIDS RESEARCH, 2012, 40 (05) : 2152 - 2167
  • [42] Cγ-Aminopropylene peptide nucleic acid (amp-PNA): chiral cationic PNAs with superior PNA:DNA/RNA duplex stability and cellular uptake
    Kumar, Pramod
    Jain, Deepak R.
    TETRAHEDRON, 2015, 71 (21) : 3378 - 3384
  • [43] Incorporating 2-Thiouracil into Short Double-Stranded RNA-Binding Peptide Nucleic Acids for Enhanced Recognition of A-U Pairs and for Targeting a MicroRNA Hairpin Precursor
    Ong, Alan Ann Lerk
    Toh, Desiree-Faye Kaixin
    Krishna, Manchugondanahalli S.
    Patil, Kiran M.
    Okamura, Katsutomo
    Chen, Gang
    BIOCHEMISTRY, 2019, 58 (32) : 3444 - 3453
  • [44] Programming the Cellular Uptake of Physiologically Stable Peptide-Gold Nanoparticle Hybrids with Single Amino Acids
    Yang, Hong
    Fung, Shan-Yu
    Liu, Mingyao
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2011, 50 (41) : 9643 - 9646
  • [45] Uptake by human glioma cell lines and biological effects of a peptide-nucleic acids targeting miR-221
    Eleonora Brognara
    Enrica Fabbri
    Elena Bazzoli
    Giulia Montagner
    Claudio Ghimenton
    Albino Eccher
    Cinzia Cantù
    Alex Manicardi
    Nicoletta Bianchi
    Alessia Finotti
    Giulia Breveglieri
    Monica Borgatti
    Roberto Corradini
    Valentino Bezzerri
    Giulio Cabrini
    Roberto Gambari
    Journal of Neuro-Oncology, 2014, 118 : 19 - 28
  • [46] Luminescent Conjugates between Dinuclear Rhenium Complexes and Peptide Nucleic Acids (PNA): Synthesis, Photophysical Characterization, and Cell Uptake
    Mari, Cristina
    Panigati, Monica
    D'Alfonso, Laura
    Zanoni, Ivan
    Donghi, Daniela
    Sironi, Laura
    Collini, Maddalena
    Maiorana, Stefano
    Baldoli, Clara
    D'Alfonso, Giuseppe
    Licandro, Emanuela
    ORGANOMETALLICS, 2012, 31 (16) : 5918 - 5928
  • [47] Conjugation of spermine enhances cellular uptake of the stapled peptide-based inhibitors of p53-Mdm2 interaction
    Muppidi, Avinash
    Li, Xiaolong
    Chen, Jiandong
    Lin, Qing
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2011, 21 (24) : 7412 - 7415
  • [48] Cell-Penetrating Peptides and Peptide Nucleic Acid-Coupled MRI Contrast Agents: Evaluation of Cellular Delivery and Target Binding
    Mishra, Ritu
    Su, Wu
    Pohmann, Rolf
    Pfeuffer, Josef
    Sauer, Martin G.
    Ugurbil, Kamil
    Engelmann, Joern
    BIOCONJUGATE CHEMISTRY, 2009, 20 (10) : 1860 - 1868
  • [49] A novel Chk1-binding peptide that enhances genotoxic sensitivity through the cellular redistribution of nuclear Chk1
    Kim, Kwang Seok
    Choi, Kyu Jin
    Bae, Sangwoo
    INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, 2016, 38 (05) : 1490 - 1498
  • [50] Drug-Loaded Polymeric Spherical Nucleic Acids: Enhancing Colloidal Stability and Cellular Uptake of Polymeric Nanoparticles through DNA Surface-Functionalization
    Banga, Resham J.
    Krovi, Sal Archana
    Narayan, Suguna P.
    Sprangers, Anthony J.
    Liu, Guoliang
    Mirkin, Chad A.
    Nguyen, SonBinh T.
    BIOMACROMOLECULES, 2017, 18 (02) : 483 - 489
12345