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Delivery of myo ‐Inositol Hexakisphosphate to the Cell Nucleus with a Proline‐Based Cell‐Penetrating Peptide
Author(s) -
Li Mao,
Puschmann Robert,
Herdlitschka Andreas,
Fiedler Dorothea,
Wennemers Helma
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202006770
Subject(s) - inositol , inositol phosphate , polyproline helix , nucleus , biophysics , chemistry , peptide , biochemistry , cationic polymerization , microbiology and biotechnology , cell , proline , stereochemistry , biology , receptor , amino acid , organic chemistry
Inositol hexakisphosphate (InsP 6 ) is a central member of the inositol phosphate messengers in eukaryotic cells. Tools to manipulate the level of InsP 6 , particularly with compartment selectivity, are needed to enable functional cellular studies. We present cationic octa‐(4S)guanidiniumproline ( Z8 ) for the delivery of InsP 6 into the cell nucleus. CD spectroscopy, binding affinity, dynamic light scattering, and computational studies revealed that Z8 binds tightly to InsP 6 and upon binding undergoes a conformational change from a PPII‐helical structure to a structure that forms aggregates. The unique conformational features of the cationic oligoproline enable complex formation and cellular delivery of InsP 6 with considerably greater efficacy than the flexible counterpart octaarginine.