TY - JOUR
T1 - Synthesis of 6-Alkynylated Purine-Containing DNA via On-Column Sonogashira Coupling and Investigation of Their Base-Pairing Properties
AU - Okamura, Hidenori
AU - Trinh, Giang Hoang
AU - Dong, Zhuoxin
AU - Fan, Wenjue
AU - Nagatsugi, Fumi
N1 - Funding Information:
This study was supported in part by the Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research on Early-Career Scientists (19K15710, 21K14749), the Program for Creation of Interdisciplinary Research by Tohoku University, Tokyo Biochemical Research Foundation, Takeda Science.
Funding Information:
G.H.T gratefully acknowledges scholarship support throughout the master’s degree from Kobayashi International Foundation.
Publisher Copyright:
© 2023 by the authors.
PY - 2023/2
Y1 - 2023/2
N2 - Synthetic unnatural base pairs have been proven to be attractive tools for the development of DNA-based biotechnology. Our group has very recently reported on alkynylated purine–pyridazine pairs, which exhibit selective and stable base-pairing via hydrogen bond formation between pseudo-nucleobases in the major groove of duplex DNA. In this study, we attempted to develop an on-column synthesis methodology of oligodeoxynucleotides (ODNs) containing alkynylated purine derivatives to systematically explore the relationship between the structure and the corresponding base-pairing ability. Through Sonogashira coupling of the ethynyl pseudo-nucleobases and CPG-bound ODNs containing 6-iodopurine, we have demonstrated the synthesis of the ODNs containing three NPu derivatives (NPu1, NPu2, NPu3) as well as three OPu derivatives (OPu1, OPu2, OPu3). The base-pairing properties of each alkynylated purine derivative revealed that the structures of pseudo-nucleobases influence the base pair stability and selectivity. Notably, we found that OPu1 bearing 2-pyrimidinone exhibits higher stability to the complementary NPz than the original OPu, thereby demonstrating the potential of the on-column strategy for convenient screening of the alkynylated purine derivatives with superior pairing ability.
AB - Synthetic unnatural base pairs have been proven to be attractive tools for the development of DNA-based biotechnology. Our group has very recently reported on alkynylated purine–pyridazine pairs, which exhibit selective and stable base-pairing via hydrogen bond formation between pseudo-nucleobases in the major groove of duplex DNA. In this study, we attempted to develop an on-column synthesis methodology of oligodeoxynucleotides (ODNs) containing alkynylated purine derivatives to systematically explore the relationship between the structure and the corresponding base-pairing ability. Through Sonogashira coupling of the ethynyl pseudo-nucleobases and CPG-bound ODNs containing 6-iodopurine, we have demonstrated the synthesis of the ODNs containing three NPu derivatives (NPu1, NPu2, NPu3) as well as three OPu derivatives (OPu1, OPu2, OPu3). The base-pairing properties of each alkynylated purine derivative revealed that the structures of pseudo-nucleobases influence the base pair stability and selectivity. Notably, we found that OPu1 bearing 2-pyrimidinone exhibits higher stability to the complementary NPz than the original OPu, thereby demonstrating the potential of the on-column strategy for convenient screening of the alkynylated purine derivatives with superior pairing ability.
KW - DNA
KW - DNA major groove
KW - Sonogashira coupling
KW - hydrogen bonds
KW - modified nucleosides
KW - solid-phase synthesis
KW - unnatural base pair
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U2 - 10.3390/molecules28041766
DO - 10.3390/molecules28041766
M3 - Article
C2 - 36838761
AN - SCOPUS:85149053384
SN - 1420-3049
VL - 28
JO - Molecules
JF - Molecules
IS - 4
M1 - 1766
ER -