Department of Chemistry and Biochemistry, University of Kitakyushu, Hibikino, Kitakyushu 808-0135, Japan.
Biomacromolecules. 2020 Dec 14;21(12):4823-4834. doi: 10.1021/acs.biomac.0c01038. Epub 2020 Nov 13.
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, dA 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.
寡聚脱氧腺嘌呤（dA）与β-1,3-葡聚糖裂褶多糖（SPG）形成新颖的 1:2 三重螺旋。我们发现，dA 精心选择最适合的 SPG 长度进行结合；例如，dA 仅与具有 30、60 或 90 个主链葡萄糖的短 SPG 链复合，并且它们彼此之间很容易分离。本研究通过使用凝胶渗透色谱法与多角度光散射和同步加速器小角度 X 射线散射相结合，证明了这种新型化学计量复合物的形成。这些寡聚 DNA/多糖复合物可用作向表达β-1,3-葡聚糖受体的免疫细胞递送治疗性寡核苷酸的工具。本研究提供了一个强大的平台技术，用于对其进行表征，符合纳米药物现代监管科学的要求，这是将候选药物推向临床试验所必需的。我们的发现对于表征这些复合物以及为核苷酸和糖化学提供新的见解非常重要。
