PPG Peptide Nucleic Acids that Promote DNA Guanine Quadruplexes

被引:6
作者
Englund, Ethan A. [1 ]
Gupta, Pankaj [1 ]
Micklitsch, Christopher M. [1 ]
Onyshchenko, Mykola I. [2 ]
Remeeva, Evgenia [2 ]
Neumann, Ronald D. [2 ]
Panyutin, Igor G. [2 ]
Appella, Daniel H. [1 ]
机构
[1] NIDDK, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA
[2] NIH, Ctr Clin, DHHS, Bethesda, MD 20892 USA
基金
美国国家卫生研究院;
关键词
DNA recognition; G-quadruplexes; nucleic acids; nucleobases; peptide nucleic acids; DUPLEX DNA; STRAND INVASION; HUMAN GENOME; PNA; SEQUENCE; OLIGODEOXYRIBONUCLEOTIDES; STABILIZATION; SPECIFICITY; INHIBITORS; STABILITY;
D O I
10.1002/cbic.201402224
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Recent studies have shown that guanine-rich (G-rich) sequences with the potential to form quadruplexes might play a role in normal transcription as well as overexpression of oncogenes. Chemical tools that allow examination of the specific roles of G-quadruplex formation in vivo, and their association with gene regulation will be essential to understanding the functions of these quadruplexes and might lead to beneficial therapies. Properly designed peptide nucleic acids (PNAs) can invade G-rich DNA duplexes and induce the formation of a G-quadruplex in the free DNA strand. Replacing guanines in the PNA sequence with pyrazolo[3,4-d]pyrimidine guanine (PPG) nucleobases eliminates G-quadruplex formation with PNA and promotes invasion of the target DNA.
引用
收藏
页码:1887 / 1890
页数:4
相关论文
共 40 条
[1]   N2-Benzyloxycarbonylguan-9-yl acetic acid derivatives as HIV-1 reverse transcriptase non-nucleoside inhibitors with decreased loss of potency against common drug-resistance mutations. [J].
Adebambo, Kassim F. ;
Zanoli, Samantha ;
Thomas, Michael G. ;
Cancio, Reynel ;
Howarth, Nicola M. ;
Maga, Giovanni .
CHEMMEDCHEM, 2007, 2 (10) :1405-1409
[2]   Peptide nucleic acid-anthraquinone conjugates: strand invasion and photoinduced cleavage of duplex DNA [J].
Armitage, B ;
Koch, T ;
Frydenlund, H ;
Orum, H ;
Batz, HG ;
Schuster, GB .
NUCLEIC ACIDS RESEARCH, 1997, 25 (22) :4674-4678
[3]   Targeting G-quadruplexes in gene promoters: a novel anticancer strategy? [J].
Balasubramanian, Shankar ;
Hurley, Laurence H. ;
Neidle, Stephen .
NATURE REVIEWS DRUG DISCOVERY, 2011, 10 (04) :261-275
[4]   Superior duplex DNA strand invasion by acridine conjugated peptide nucleic acids [J].
Bentin, T ;
Nielsen, PE .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2003, 125 (21) :6378-6379
[5]  
Biffi G, 2014, NAT CHEM, V6, P75, DOI [10.1038/NCHEM.1805, 10.1038/nchem.1805]
[6]  
Biffi G, 2013, NAT CHEM, V5, P182, DOI [10.1038/NCHEM.1548, 10.1038/nchem.1548]
[7]   STRUCTURE AND FUNCTION OF TELOMERES [J].
BLACKBURN, EH .
NATURE, 1991, 350 (6319) :569-573
[8]   DNA secondary structures: stability and function of G-quadruplex structures [J].
Bochman, Matthew L. ;
Paeschke, Katrin ;
Zakian, Virginia A. .
NATURE REVIEWS GENETICS, 2012, 13 (11) :770-780
[9]   PD-loop: A complex of duplex DNA with an oligonucleotide [J].
Bukanov, NO ;
Demidov, VV ;
Nielsen, PE ;
Frank-Kamenetskii, MD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (10) :5516-5520
[10]   Quadruplex DNA: sequence, topology and structure [J].
Burge, Sarah ;
Parkinson, Gary N. ;
Hazel, Pascale ;
Todd, Alan K. ;
Neidle, Stephen .
NUCLEIC ACIDS RESEARCH, 2006, 34 (19) :5402-5415