The Role of Small-Angle X-Ray Scattering and Molecular Simulations in 3D Structure Elucidation of a DNA Aptamer Against Lung Cancer

Morozov D, Mironov V, Moryachkov R, Shchugoreva I, Artyushenko P, Zamay G, Kolovskaya O, Zamay T, Krat A, Molodenskiy D, Zabluda V, Veprintsev D, Sokolov A, Zukov R, Berezovski M, Tomilin F, Fedorov D, Alexeev Y, Kichkailo A, Molecular Therapy - Nucleic Acids (2021) DOI

SASDK36 – LC-18t - ssDNA aptamer specific to lung adenocarcinoma cancer cells

Lung adenocarcinoma aptamer, truncated version
MWexperimental 12 kDa
MWexpected 11 kDa
VPorod 16 nm3
log I(s) 1.24×10-2 1.24×10-3 1.24×10-4 1.24×10-5
Lung adenocarcinoma aptamer, truncated version small angle scattering data  s, nm-1
ln I(s)
Lung adenocarcinoma aptamer, truncated version Guinier plot ln 1.24×10-2 Rg: 2.1 nm 0 (2.1 nm)-2 s2
(sRg)2I(s)/I(0)
Lung adenocarcinoma aptamer, truncated version Kratky plot 1.104 0 √3 sRg
p(r)
Lung adenocarcinoma aptamer, truncated version pair distance distribution function Rg: 2.1 nm 0 Dmax: 6.7 nm

Data validation

Fits and models

log I(s)
 s, nm-1
Lung adenocarcinoma aptamer, truncated version GROMACS model
log I(s)
 s, nm-1
Lung adenocarcinoma aptamer, truncated version DAMMIF model
SAXS measurements were performed at the P12 BioSAXS beamline of the EMBL at the Petra III storage ring (DESY, Hamburg). The data were collected on a photon-counting Pilatus-6M detector at the sample-to-detector distance of 3.0 m and wavelength λ of 0.12 nm covering the momentum vector range 0.2 < s < 7.8 nm −1 (s = 4πsinθ/λ, where 2θ is the scattering angle). The scattering patterns from the dilution series were collected at four different concentrations: 8, 4, 2 and 1 mg/ml, each in a volume of 50 uL.

Lung adenocarcinoma aptamer, truncated version (LC-18t)
Mol. type   DNA
Organism   Artificially synthesized
Olig. state   Monomer
Mon. MW   10.8 kDa
Sequence   FASTA