2021 Fiscal Year Final Research Report
Design and evaluation of artificial nucleic acid covering various point mutations of genes.
Project/Area Number |
19K05584
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 35010:Polymer chemistry-related
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Research Institution | Tottori University |
Principal Investigator |
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Keywords | ペプチド核酸 / KRAS遺伝子 / アンチセンス核酸医薬 / ヒポキサンチン / 相補鎖形成 |
Outline of Final Research Achievements |
In this study, we synthesized a PNA monomer with hypoxanthin (Hyp) at the side chain, which forms a comprehensive base pair with citocin (C), adenin (A), timine (T), and uracil (U), and we investigated the application to nucleic acid medicines corresponding to point mutations by analyzing the complementary hybridization behavior of oligo PNA and synDNA. As a result, in the comprehensive complementary chain formation of C, A, and T other than G, the difference between the values (delta-G at 37℃) of GGT and GTT at is estimated to be 0.17 kcal / mol, which makes it difficult to recognize G and T. This means that it is difficult for oligo PNA to comprehensively recognize anything other than G. On the other hand, the difference between the values of delta-G at 37℃ between WT (GGT) and MT (GCT) is estimated to be 2.75 kcal / mol, It was suggested that it could be applied to other single nucleotide polymorphic disease in which the wild type is cytosine.
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Free Research Field |
生体分子化学
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Academic Significance and Societal Importance of the Research Achievements |
KRAS遺伝子のexon2codon12を中心とした多様な点突然変異はすい臓がんの90%、大腸がんの40%にみられ、がん疾患全体の約40%に生じる遺伝子変異である.この変異により,最新の分子標的薬(抗EGFR抗体薬)の薬効が期待できない問題点を引き起こすが、変異のパターンは多様であるため、それぞれに対応した核酸医薬を開発しなければならない.ヒポキサンチンがゆらぎ塩基として作用することに着目し、細胞内で正常な塩基配列とそれ以外の点突然変異群を識別する新たな核酸モデルの設計と物性評価は、多様な変異を網羅したアンチセンス型核酸医薬としての展開が可能となる.
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