Development of stimuli responsible water-soluble functional polymers for biomedical purpose: Creating ischemia cell specific oligonucleotide therapeutics system with environment-responsive peptide ribonucleic acids (PRNAs)

Research output: Contribution to journalReview articlepeer-review

Abstract

We have reported a series of novel artificial nucleic acids, named Peptide Ribonucleic Acids (PRNAs), as promising candidates for ischemic/hypoxic cell specific oligonucleotide therapeutics. PRNAs are consisted with γ- and/or α-glutamate peptide backbone and 5′-amino ribonucleoside moiety in the side chain. For applying ischemic/hypoxic cell specificificity, PRNAs containing phenylboronic acid moiety with appropriate substients (PRNA-PBA) were synthesized. Under the normal cellular condition (pH = 7.2), the PRNA-PBA unit forms intramolecular cyclic borate ester with 2:3′-cis-diole of PRNA's furanose residue, and then PRNA's nucleobase preferres syn orientation, which is no recognition/complexation ability with any nucleobases of RNA and/or DNA. On the other hand, under the ischemic/hypoxic cellular conditions (pH 6.2 ∼ 5.8), the pH triggered nucleobase-orientation switching of PRNA from syn to anti is induced by dissociation of the borate ester and then anti oriented nuclobases of PRNAs recognize and form stable complex with target functional RNA, which is an essential function of oligonucleotide therapeutics strategy. Therefore, PRNAs expect to be intracellular environment condition responsible artificial nucleic acids for oligonucleotide therapeutics strategy, and then can discriminate ischemic/hypoxic cells and normal cell.

Original languageEnglish
Pages (from-to)416-419
Number of pages4
JournalKobunshi
Volume65
Issue number8
Publication statusPublished - 2016 Aug

Keywords

  • Artificial nucleic acid
  • Cancer cell spesific
  • Ischemia
  • Oligonucleotide therapeutics
  • Orientation control
  • PH responsible
  • Recognition control
  • Stimli responsible

ASJC Scopus subject areas

  • Chemical Engineering(all)

Fingerprint Dive into the research topics of 'Development of stimuli responsible water-soluble functional polymers for biomedical purpose: Creating ischemia cell specific oligonucleotide therapeutics system with environment-responsive peptide ribonucleic acids (PRNAs)'. Together they form a unique fingerprint.

Cite this