Synthesis and purification of self-assembling peptide-oligonucleotide conjugates by solid-phase peptide fragment condensation

Mahnseok Kye, Yong-beom Lim

Research output: Contribution to journalArticle

Abstract

Peptide-oligonucleotide conjugates (POCs) are interesting molecules as they covalently combine 2 of the most important biomacromolecules. Sometimes, the synthesis of POCs involves unexpected difficulties; however, POCs with self-assembling propensity are even harder to synthesize and purify. Here, we show that solid-phase peptide fragment condensation combined with thiol-maleimide or copper-catalyzed azide-alkyne cycloaddition click chemistries is useful for the syntheses of self-assembling POCs. We describe guidelines for the selection of reactive functional groups and their placement during the conjugation reaction and consider the cost-effectiveness of the reaction. Purification is another important challenge during the preparation of POCs. Our results show that polyacrylamide gel electrophoresis under denaturing conditions is most suitable to recover a high yield of self-assembling POCs. This report provides the first comprehensive study of the preparation of self-assembling POCs, which will lay a foundation for the development of elegant and sophisticated molecular assemblies.

Original languageEnglish
Article numbere3092
JournalJournal of Peptide Science
Volume24
Issue number8-9
DOIs
Publication statusPublished - 2018 Aug 1

Fingerprint

Peptide Fragments
Oligonucleotides
Purification
Condensation
Peptides
Click Chemistry
Alkynes
Azides
Cycloaddition
Cycloaddition Reaction
Cost effectiveness
Electrophoresis
Sulfhydryl Compounds
Functional groups
Cost-Benefit Analysis
Copper
Polyacrylamide Gel Electrophoresis
Guidelines
Molecules

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

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Synthesis and purification of self-assembling peptide-oligonucleotide conjugates by solid-phase peptide fragment condensation. / Kye, Mahnseok; Lim, Yong-beom.

In: Journal of Peptide Science, Vol. 24, No. 8-9, e3092, 01.08.2018.

Research output: Contribution to journalArticle

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