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A Branched Tripeptide with an Anion‐Binding Motif as a New Delivery Carrier for Efficient Gene Transfection
Author(s) -
Jiang Hao,
Hu XiaoYu,
Mosel Stefanie,
Knauer Shirley K.,
Hirschhäuser Christoph,
Schmuck Carsten
Publication year - 2019
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201800728
Subject(s) - tripeptide , isothermal titration calorimetry , chemistry , transfection , gene delivery , dna condensation , cationic polymerization , dna , peptide , stereochemistry , combinatorial chemistry , biochemistry , gene , organic chemistry
Branched and dendrimeric cationic peptides have shown better transfection efficiency than linear peptides, owing to their superior capacity for inducing DNA condensation. We have designed and synthesized two analogously guanidinocarbonylpyrrole‐substituted (GCP‐substituted) branched cationic tripeptides that provide extremely strong electrostatic attraction towards DNA. Both ligands 1 and 2 can bind to DNA and form condensed complexes, owing to the branched structure and high positive charges, as demonstrated by isothermal titration calorimetry (ITC), ζ potential and atomic force microscopy (AFM). After the replacement of the carboxylate group by an amide group, binding of ligand 2 to DNA shows exothermic enthalpy and positive entropy changes relative to ligand 1 . Rational interpretation would suggest that ligand 2 might aid the translocation of plasmid pF143 to HEK 293T cells, showing high gene transfection efficiency. This work therefore provides a facile way, by modifying a branched cationic tripeptide with GCP, to turn a peptide even a tripeptide into an efficient gene transfection vector.