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Synthesis and purification of self‐assembling peptide‐oligonucleotide conjugates by solid‐phase peptide fragment condensation
Author(s) -
Kye Mahnseok,
Lim Yongbeom
Publication year - 2018
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.3092
Subject(s) - chemistry , peptide , combinatorial chemistry , maleimide , conjugate , oligonucleotide , click chemistry , solid phase synthesis , yield (engineering) , covalent bond , peptide synthesis , organic chemistry , biochemistry , materials science , dna , mathematical analysis , mathematics , metallurgy
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.