NMR screen reveals the diverse structural landscape of a G-quadruplex library

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F24%3A00598148" target="_blank" >RIV/61388963:_____/24:00598148 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/24:10490216 RIV/00216208:11320/24:10490216

Výsledek na webu

<a href="https://doi.org/10.1002/chem.202401437" target="_blank" >https://doi.org/10.1002/chem.202401437</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/chem.202401437" target="_blank" >10.1002/chem.202401437</a>

Jazyk výsledku

angličtina

Název v původním jazyce

NMR screen reveals the diverse structural landscape of a G-quadruplex library

Popis výsledku v původním jazyce

G-quadruplexes are noncanonical nucleic acid structures formed by stacked guanine tetrads.Despite their functional and structural diversity, a single consensus model is typically used to describe sequences with the potential to form G-quadruplex structures. We are interested in developing more specific sequence models for G-quadruplexes. In previous work, we functionally characterized each sequence in a 496-member library of variants of a monomeric reference G-quadruplex for the ability to bind GTP, promote a model peroxidase reaction, generate intrinsic fluorescence, and to form multimers. Here we used NMR to obtain a broad overview of the structural features of this library. After determining the1H NMR spectrum of each of these 496 sequences, spectra were sorted into multiple classes, most of which could be rationalized based on mutational patterns in the primary sequence. A more detailed screen using representative sequences provided additional information about spectral classes, and confirmed that the classes determined based on analysis of1H NMR spectra are correlated with functional categories identified in previous studies. These results provide new insights into the surprising structural diversity of this library. They also show how NMR can be used to identify classes of sequences with distinct mutational signatures and functions.

Název v anglickém jazyce

NMR screen reveals the diverse structural landscape of a G-quadruplex library

Popis výsledku anglicky

G-quadruplexes are noncanonical nucleic acid structures formed by stacked guanine tetrads.Despite their functional and structural diversity, a single consensus model is typically used to describe sequences with the potential to form G-quadruplex structures. We are interested in developing more specific sequence models for G-quadruplexes. In previous work, we functionally characterized each sequence in a 496-member library of variants of a monomeric reference G-quadruplex for the ability to bind GTP, promote a model peroxidase reaction, generate intrinsic fluorescence, and to form multimers. Here we used NMR to obtain a broad overview of the structural features of this library. After determining the1H NMR spectrum of each of these 496 sequences, spectra were sorted into multiple classes, most of which could be rationalized based on mutational patterns in the primary sequence. A more detailed screen using representative sequences provided additional information about spectral classes, and confirmed that the classes determined based on analysis of1H NMR spectra are correlated with functional categories identified in previous studies. These results provide new insights into the surprising structural diversity of this library. They also show how NMR can be used to identify classes of sequences with distinct mutational signatures and functions.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/EH22_008%2F0004575" target="_blank" >EH22_008/0004575: RNA pro terapii</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Chemistry - A European Journal

ISSN

0947-6539

e-ISSN

1521-3765

Svazek periodika

30

Číslo periodika v rámci svazku

67

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

11

Strana od-do

e202401437

Kód UT WoS článku

001354202900001

EID výsledku v databázi Scopus

2-s2.0-85208636396