Delivery ofmyo-Inositol Hexakisphosphate to the Cell Nucleus with a Proline-Based Cell-Penetrating Peptide

被引：17

作者：

Li, Mao ^{[1
]}

Puschmann, Robert ^{[2
,3
]}

Herdlitschka, Andreas ^{[1
]}

Fiedler, Dorothea ^{[2
,3
]}

Wennemers, Helma ^{[1
]}

机构：

[1] Swiss Fed Inst Technol, Lab Organ Chem, Vladimir Prelog Weg 3, CH-8093 Zurich, Switzerland

[2] Leibniz Forschungsinst Mol Pharmakol, Robert Rossle Str 10, D-13125 Berlin, Germany

[3] Humboldt Univ, Inst Chem, Brook Taylor Str 2, D-12489 Berlin, Germany

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2020年 / 59卷 / 36期

关键词：

cell-penetrating peptides; drug delivery; cellular delivery; inositol phosphate; molecular recognition; GENE DELIVERY; BINDING; WATER; POLYPHOSPHATES; RECOGNITION; GUANIDINIUM; MOLECULES; PATHWAY; DESIGN;

D O I：

10.1002/anie.202006770

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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 thatZ8binds 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.

引用

页码：15586 / 15589

页数：4

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