1997 Fiscal Year Final Research Report Summary
MOLECULAR DESIGN OF NEW EFFECTIVE ANTISENSE NUCLEIC ACIDS CAPABLE OF HYBRIDIZATION TO THE TARGET NENES
| Project/Area Number |
07408014
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Bioorganic chemistry
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| Research Institution | TOKYO INSTITUTE OF TECHNOLOGY |
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Principal Investigator |
SEKINE Mitsuo TOKYO INSTITUTE OF TECHNOLOGY,FACULTY OF BIOSCIENCE AND BIOTECHNOLOGY,ASSOCIATE PROFESSOR, 生命理工学部, 助教授 (40111679)
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| Co-Investigator(Kenkyū-buntansha) |
WADA Takeshi TOKYO INSTITUTE OF TECHNOLOGY,FACULTY OF BIOSCIENCE AND BIOTECHNOLOGY,DEPARTMENT, 生命理工学部, 助手 (90240548)
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| Project Period (FY) |
1995 – 1997
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| Keywords | ANTISENCE NUCLEIC ACID / CONFORMATION / 3'-ENDO / CYCLOURIDYLIC ACID / INTRAMOLECULAR CYCLIZATION / MOLECULAR MECHANICS / SOLID PHASE SYNTHESIS / DUPLEX FORMATION |
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| Research Abstract |
A 2'-O-methyluridylic acid derivative having a cyclic structure linked between the 5-position of the uracil residue and the 5'-phosphate group was synthesized. The NMR analysis of suggests that this cyclouridylic acid derivative has exclusively the C3'-endo conformation which is in favor of duplex formation with RNA.Two oligonucleotides [pc3Um(pT)_9 and pc3Um(pU)_9]incorporating this cyclouridylic acid unit at the 5'-terminal site were synthesized by using the fully protected cyclouridylic acid 3'-phosphoramidite derivative in the solid phase synthsis. To examine the actual effect of this cyclic structure on the thermal stability of duplexes between the modified oligonucleotides and their complementary oligonucleotides, two oligonucleotides [pUm(pT)_9 and pUm(pU)_9] having an acyclic structure were also synthesized. As the complementary oligonucleotides, dA(pdA)_9 and A(pA)_9 were used for Tm experiments with these 5'-terminal modified oligonucleotides. The Tm values of all possible duplexes were measured. These results clearly show that there the duplex of A(pA)_9/pc3Um(pT)_9 has a higher Tm value by 5.5ﾟC than that of A(pA)_9/T(pT)_9. This is rather significant compared with all other cases. Moreover, the Tm value of A(pA)_9/pc3Um(pT)_9 is 4.5ﾟC higher than that of A(pA)_9/pUm(pT)_9. This result suggests that the cyclic structure can considerably contribute to stabilization of the duplex only in the case of the modified oligomer (DNA) and decaadenylate (RNA).
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