High-Affinity Nucleic-Acid-Based Receptors for Steroids.
ACS Chem Biol
; 12(12): 3103-3112, 2017 12 15.
Article
en En
| MEDLINE
| ID: mdl-29083858
ABSTRACT
Artificial receptors for hydrophobic molecules usually have moderate affinities and limited selectivities. We describe three new classes of high affinity hydrophobic receptors for nonaromatic steroids based on deoxyribonucleotides, obtained through five high stringency selections coupled with tailored counter-selections. The isolation of multiple classes of high affinity steroid receptors demonstrates the surprising breadth of moderately sized hydrophobic binding motifs (<40 nucleotides) available to natural nucleic acids. Studies of interactions with analogs indicate that two classes, four-way junctions and 4XGN motifs, comprise receptors with shapes that prevent binding of specific steroid conjugates used in counter-selections. Furthermore, they strongly prefer nonhydroxylated steroid cores, which is typical for hydrophobic receptors. The third new class accommodates hydroxyl groups in high-affinity, high-selectivity binding pockets, thus reversing the preferences of the first two classes. The high-affinity binding of aptamers to targets efficiently inhibits double-helix formation in the presence of the complementary oligonucleotides. The high affinity of some of these receptors and tailored elimination of binding through counter-selections ensures that these new aptamers will enable clinical chemistry applications.
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Bases de datos:
MEDLINE
Asunto principal:
Esteroides
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Ácidos Nucleicos
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Receptores de Esteroides
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Sulfato de Deshidroepiandrosterona
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Desoxicorticosterona
Idioma:
En
Revista:
ACS Chem Biol
Año:
2017
Tipo del documento:
Article