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1.
Chembiochem ; 18(2): 185-188, 2017 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-27870530

RESUMO

A supramolecular approach was undertaken to create functionally activatable cell-penetrating peptides. Two tetra-arginines were assembled into an active cell-penetrating peptide by heterodimerizing leucine zippers. Three different leucine-zipper pairs were evaluated: activation was found to depend on the association constant of the coiled-coil peptides. The weaker-binding peptides required an additional disulfide linkage to induce cell-penetrating capability, whereas for the most-stable coiled-coil no additional stabilization was needed. The latter zipper pair was used to show that the induced formation of the coiled coils allows control over the uptake of an oligoarginine CPP-conjugated cargo protein.


Assuntos
Peptídeos Penetradores de Células/metabolismo , Oligopeptídeos/metabolismo , Arginina/química , Arginina/metabolismo , Peptídeos Penetradores de Células/química , Dicroísmo Circular , Dimerização , Endocitose , Citometria de Fluxo , Fluoresceína-5-Isotiocianato/química , Células HeLa , Humanos , Zíper de Leucina , Microscopia Confocal , Oligopeptídeos/química
2.
Bioconjug Chem ; 26(5): 850-6, 2015 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-25915685

RESUMO

Activatable cell-penetrating peptides are of great interest in drug delivery because of their enhanced selectivity which can be controlled by the external stimuli that trigger their activation. The use of a specific enzymatic reaction to trigger uptake of an inert peptide offers a relevant targeting strategy because the activation process takes place in a short time and only in areas where the specific cell surface enzyme is present. To this aim, the lysine side chain of Tat peptides was modified with an enzyme-cleavable domain of minimal size. This yielded blocked Tat-peptides which were inactive but that could be activated by coincubation with the selected enzymes.


Assuntos
Aminopeptidases/metabolismo , Peptídeos Penetradores de Células/química , Peptídeos Penetradores de Células/metabolismo , Dipeptidil Peptidases e Tripeptidil Peptidases/metabolismo , Sequência de Aminoácidos , Produtos do Gene tat/química , Produtos do Gene tat/metabolismo , Células HEK293 , Humanos , Lisina/química
3.
Chem Sci ; 10(3): 701-705, 2019 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-30746105

RESUMO

Cell-penetrating peptides are able to transport a wide variety of cargo across cell membranes. Although promising, they are not often considered for therapeutic purposes as they lack controllable activity and cell selectivity. We have developed an activation strategy based on a split octa-arginine cell-penetrating peptide (CPP) that can be activated by means of bioorthogonal ligation. To this end we prepared two non-penetrating tetra-arginine halves, functionalized either with a tetrazine or with a complementary bicyclo[6.1.0]nonyne (BCN) group. We demonstrate that an active octa-arginine can be reconstituted in situ upon mixing the complementary split peptides. The resulting activated peptide is taken up as efficiently as the well-established cell-penetrating peptide octa-arginine. The activation of the oligo-arginines can also be achieved using trans-cyclooctene (TCO) as a ligation partner, while norbornene appears too kinetically slow for use in situ. We further show that this strategy can be applied successfully to transport a large protein into living cells. Our results validate a promising first step in achieving control over cell penetration and to use CPPs for therapeutic approaches.

4.
J Appl Lab Med ; 6(4): 1067-1071, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-33444452
5.
Chem Commun (Camb) ; 50(4): 415-7, 2014 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-24247922

RESUMO

A small library of oligoarginine peptides equipped with terminal cysteines was studied with respect to their cell-penetrating properties. The peptides themselves were inactive but gained the ability to enter cells upon extension of their sequence through disulfide bridge formation.


Assuntos
Peptídeos Penetradores de Células/química , Dissulfetos/química , Peptídeos Penetradores de Células/metabolismo , Citometria de Fluxo , Fluoresceína-5-Isotiocianato/química , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Microscopia Confocal
6.
Chem Commun (Camb) ; 48(57): 7179-81, 2012 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-22692031

RESUMO

A small library of cell-penetrating peptides (CPPs) containing a minimized cationic domain and a lipophilic domain of different size was studied. CPPs that could self-assemble were found to enter cells more efficiently, triggering a glycosaminoglycan-dependent pathway.


Assuntos
Peptídeos Penetradores de Células/química , Peptídeos Penetradores de Células/metabolismo , Glicosaminoglicanos/metabolismo , Inibidores de Proteínas Quinases/administração & dosagem , Sequência de Aminoácidos , Animais , Células CHO , Permeabilidade da Membrana Celular , Cricetinae , Endocitose , Dados de Sequência Molecular , Biblioteca de Peptídeos
7.
Nanoscale ; 3(6): 2376-89, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21461437

RESUMO

Chemical reactions are traditionally carried out in bulk solution, but in nature confined spaces, like cell organelles, are used to obtain control in time and space of conversion. One way of studying these reactions in confinement is the development and use of small reaction vessels dispersed in solution, such as vesicles and micelles. The utilization of protein cages as reaction vessels is a relatively new field and very promising as these capsules are inherently monodisperse, in that way providing uniform reaction conditions, and are readily accessible to both chemical and genetic modifications. In this review, we aim to give an overview of the different kinds of nanoscale protein cages that have been employed as confined reaction spaces.


Assuntos
Nanoestruturas/química , Nanotecnologia/métodos , Proteínas/química , Reatores Biológicos , Fenômenos Químicos
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