Synthesis of 6-Alkynylated Purine-Containing DNA Via On-Column Sonogashira Coupling and Investigation of Their Base-Pairing Properties

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2023 Feb 25

PMID 36838761

Authors

Hidenori Okamura

Giang Hoang Trinh

Zhuoxin Dong

Wenjue Fan

Fumi Nagatsugi

Affiliations

Soon will be listed here.

Abstract

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 Pu derivatives (Pu1, Pu2, Pu3) as well as three Pu derivatives (Pu1, Pu2, Pu3). 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 Pu1 bearing 2-pyrimidinone exhibits higher stability to the complementary Pz than the original Pu, thereby demonstrating the potential of the on-column strategy for convenient screening of the alkynylated purine derivatives with superior pairing ability.

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