Oligo-DNA Stoichiometrically Binds β-1,3-Glucan with the Best Fit Length

Oligo-deoxyadenylic acid (dA) forms a novel 1:2 triple-helix with β-1,3-d-glucan schizophyllan (SPG). We found that dA meticulously selects the most suitable length of SPG to bind; for example, dA₃₀ only complexes with a short SPG chain having 30, 60, or 90 main-chain glucoses, and they can be easily isolated with each other. This study demonstrated such a novel stoichiometric complex formation by using gel permeation chromatography coupled with multi-angle light scattering and synchrotron small-angle X-ray scattering. These oligo-DNA/polysaccharide complexes can be used as a tool for delivering therapeutic oligonucleotides to immunocytes that express the β-1,3-d-glucan receptors. The present study provides a robust platform technique to characterize them in terms of modern regulatory science of nanomedicines, which is requisite to transfer drug candidates into clinical trial. Our findings are important for characterizing these complexes as well as for providing a new insight into nucleotide and saccharide chemistry.