Boron-containing aptamers to ATP

Boron neutron capture therapy (BNCT), an experimental treatment for certain cancers, destroys only cells near the boron; however, there is a need to develop highly specific delivery agents. As nucleic acid aptamers recognize specific molecular targets, we investigated the influence of boronated nucl...

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Vydáno v:Nucleic acids research Ročník 30; číslo 6; s. 1401 - 1407
Hlavní autor: Lato, S. M.
Médium: Journal Article
Jazyk:angličtina
Vydáno: England Oxford Publishing Limited (England) 15.03.2002
Oxford University Press
Témata:
Adenosine Triphosphate - analogs & derivatives
Adenosine Triphosphate - metabolism
aptamers
ATP
Base Sequence
Binding Sites
Boron
Boron - chemistry
Boron Neutron Capture Therapy
Directed Molecular Evolution
Molecular Sequence Data
Neoplasms - radiotherapy
Nucleic Acid Conformation
Nucleic acids
Oligoribonucleotides - chemistry
Oligoribonucleotides - metabolism
Sequence Alignment
ISSN:1362-4962, 0305-1048, 1362-4962
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Shrnutí:Boron neutron capture therapy (BNCT), an experimental treatment for certain cancers, destroys only cells near the boron; however, there is a need to develop highly specific delivery agents. As nucleic acid aptamers recognize specific molecular targets, we investigated the influence of boronated nucleotide analogs on RNA function and on the systematic evolution of ligands by exponential enrichment (SELEX) process. Substitution of guanosine 5'-(alpha-P-borano) triphosphate (bG) for GTP or uridine 5'-(alpha-P-borano) triphosphate (bU) for UTP in several known aptamers diminished or eliminated target recognition by those RNAs. Specifically, ATP-binding aptamers containing the zeta-fold, which appears in several selections for adenosine aptamers, became inactive upon bG substitution but were only moderately affected by bU substitution. Selections were carried out using the bG or bU analogs with C8-linked ATP agarose as the binding target. The selections with bU and normal NTP yielded some zeta-fold aptamers, while the bG selection yielded none of this type. Non-zeta aptamers from bU and bG populations tolerated the borano substitution and many required it. The borano nucleotide requirement is specific; bU could not be used in bG-dependent aptamers nor vice versa. The borano group plays an essential role, as yet undefined, in target recognition or RNA structure. We conclude that the bG and bU nucleotides are fully compatible with SELEX, and that these analogs could be used to make boronated aptamers as therapeutics for BNCT.
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To whom correspondence should be addressed. Tel: +1 812 856 4977; Fax: +1 812 855 8300; Email: dhburke@indiana.edu Present address:Susan M. Lato, NuGen Technologies, 821 Industrial Road, Unit A, San Carlos, CA 94070, USA
ISSN:1362-4962
0305-1048
1362-4962
DOI:10.1093/nar/30.6.1401