Development of the 12-Base Short Dimeric Myogenetic Oligodeoxynucleotide That Induces Myogenic Differentiation.

Autor:	Umezawa, Koji, Ikeda, Rena, Sakamoto, Taiichi, Enomoto, Yuya, Nihashi, Yuma, Shinji, Sayaka, Shimosato, Takeshi, Kagami, Hiroshi, Takaya, Tomohide
Předmět:	ALKALOIDS POLYACRYLAMIDE gel electrophoresis NUCLEAR magnetic resonance ISOQUINOLINE alkaloids NUCLEIC acids APTAMERS MOLECULAR dynamics NUCLEOLIN
Zdroj:	BioTech; Jun2024, Vol. 13 Issue 2, p11, 16p
Abstrakt:	A myogenetic oligodeoxynucleotide (myoDN), iSN04 (5′-AGA TTA GGG TGA GGG TGA-3′), is a single-stranded 18-base telomeric DNA that serves as an anti-nucleolin aptamer and induces myogenic differentiation, which is expected to be a nucleic acid drug for the prevention of disease-associated muscle wasting. To improve the drug efficacy and synthesis cost of myoDN, shortening the sequence while maintaining its structure-based function is a major challenge. Here, we report the novel 12-base non-telomeric myoDN, iMyo01 (5′-TTG GGT GGG GAA-3′), which has comparable myogenic activity to iSN04. iMyo01 as well as iSN04 promoted myotube formation of primary-cultured human myoblasts with upregulation of myogenic gene expression. Both iMyo01 and iSN04 interacted with nucleolin, but iMyo01 did not bind to berberine, the isoquinoline alkaloid that stabilizes iSN04. Nuclear magnetic resonance revealed that iMyo01 forms a G-quadruplex structure despite its short sequence. Native polyacrylamide gel electrophoresis and a computational molecular dynamics simulation indicated that iMyo01 forms a homodimer to generate a G-quadruplex. These results provide new insights into the aptamer truncation technology that preserves aptamer conformation and bioactivity for the development of efficient nucleic acid drugs. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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