Novel cleavable cell-penetrating peptide-drug conjugates: synthesis and characterization

2014 ◽  
Vol 20 (5) ◽  
pp. 323-333 ◽  
Author(s):  
Marco Lelle ◽  
Stefanie U. Frick ◽  
Kerstin Steinbrink ◽  
Kalina Peneva
Keyword(s):  
Synthesis And Characterization ◽  
Cell Penetrating Peptide ◽  
Peptide Drug ◽  
Drug Conjugates ◽  
Cell Penetrating ◽  
Peptide Drug Conjugates

scholarly journals Coupling the Antimalarial Cell Penetrating Peptide TP10 to Classical Antimalarial Drugs Primaquine and Chloroquine Produces Strongly Hemolytic Conjugates

Molecules ◽  
2019 ◽  
Vol 24 (24) ◽  
pp. 4559 ◽  
Author(s):  
Luísa Aguiar ◽  
Arnau Biosca ◽  
Elena Lantero ◽  
Jiri Gut ◽  
Nuno Vale ◽  
...  
Keyword(s):  
Cell Penetrating Peptides ◽  
Antiplasmodial Activity ◽  
Erythrocyte Membranes ◽  
Cell Penetrating Peptide ◽  
Peptide Conjugates ◽  
Drug Conjugates ◽  
Cell Penetrating ◽  
A Cell ◽  
Peptide Drug Conjugates ◽  
The Cost

Recently, we disclosed primaquine cell penetrating peptide conjugates that were more potent than parent primaquine against liver stage Plasmodium parasites and non-toxic to hepatocytes. The same strategy was now applied to the blood-stage antimalarial chloroquine, using a wide set of peptides, including TP10, a cell penetrating peptide with intrinsic antiplasmodial activity. Chloroquine-TP10 conjugates displaying higher antiplasmodial activity than the parent TP10 peptide were identified, at the cost of an increased hemolytic activity, which was further confirmed for their primaquine analogues. Fluorescence microscopy and flow cytometry suggest that these drug-peptide conjugates strongly bind, and likely destroy, erythrocyte membranes. Taken together, the results herein reported put forward that coupling antimalarial aminoquinolines to cell penetrating peptides delivers hemolytic conjugates. Hence, despite their widely reported advantages as carriers for many different types of cargo, from small drugs to biomacromolecules, cell penetrating peptides seem unsuitable for safe intracellular delivery of antimalarial aminoquinolines due to hemolysis issues. This highlights the relevance of paying attention to hemolytic effects of cell penetrating peptide-drug conjugates.

Source and exploration of the peptides used to construct peptide-drug conjugates

2021 ◽  
pp. 113712
Author(s):  
Jiaqi Zhou ◽  
Yuanyuan Li ◽  
Wenlong Huang ◽  
Wei Shi ◽  
Hai Qian
Keyword(s):  
Peptide Drug ◽  
Drug Conjugates ◽  
Peptide Drug Conjugates

From Nanofibers to Nanorods: Nanostructure of Peptide-Drug Conjugates Regulated by Polypeptide-PEG Derivative and Enhanced Antitumor Effect

2018 ◽  
Vol 29 (2) ◽  
pp. 1806058 ◽  
Author(s):  
Rui Chen ◽  
Jingjing Wang ◽  
Chen Qian ◽  
Yujie Ji ◽  
Chenqi Zhu ◽  
...  
Keyword(s):  
Antitumor Effect ◽  
Peptide Drug ◽  
Drug Conjugates ◽  
Peptide Drug Conjugates

scholarly journals Intracellular Delivery System for Antibody–Peptide Drug Conjugates

2015 ◽  
Vol 23 (5) ◽  
pp. 907-917 ◽  
Author(s):  
Geoffrey Y Berguig ◽  
Anthony J Convertine ◽  
Shani Frayo ◽  
Hanna B Kern ◽  
Erik Procko ◽  
...  
Keyword(s):  
Delivery System ◽  
Intracellular Delivery ◽  
Peptide Drug ◽  
Drug Conjugates ◽  
Peptide Drug Conjugates

Controlled release of free doxorubicin from peptide–drug conjugates by drug loading

2014 ◽  
Vol 191 ◽  
pp. 123-130 ◽  
Author(s):  
Zhipeng Chen ◽  
Pengcheng Zhang ◽  
Andrew G. Cheetham ◽  
Jae Hyon Moon ◽  
James W. Moxley ◽  
...  
Keyword(s):  
Controlled Release ◽  
Drug Loading ◽  
Peptide Drug ◽  
Drug Conjugates ◽  
Free Doxorubicin ◽  
Peptide Drug Conjugates

scholarly journals Self-assembly behaviours of peptide–drug conjugates: influence of multiple factors on aggregate morphology and potential self-assembly mechanism

2018 ◽  
Vol 5 (4) ◽  
pp. 172040 ◽  
Author(s):  
Qin Fan ◽  
Yujie Ji ◽  
Jingjing Wang ◽  
Li Wu ◽  
Weidong Li ◽  
...  
Keyword(s):  
Self Assembly ◽  
Molecular Design ◽  
Peptide Drug ◽  
Extrinsic Factors ◽  
Aromatic Fragment ◽  
Multiple Factors ◽  
Drug Conjugates ◽  
Assembly Mechanism ◽  
Aggregate Morphology ◽  
Peptide Drug Conjugates

Peptide–drug conjugates (PDCs) as self-assembly prodrugs have the unique and specific features to build one-component nanomedicines. Supramolecular structure based on PDCs could form various morphologies ranging from nanotube, nanofibre, nanobelt to hydrogel. However, the assembly process of PDCs is too complex to predict or control. Herein, we investigated the effects of extrinsic factors on assembly morphology and the possible formation of nanostructures based on PDCs. To this end, we designed a PDC consisting of hydrophobic drug ( S )-ketoprofen (Ket) and valine–glutamic acid dimeric repeats peptide (L-VEVE) to study their assembly behaviour. Our results showed that the critical assembly concentration of Ket-L-VEVE was 0.32 mM in water to form various nanostructures which experienced from micelle, nanorod, nanofibre to nanoribbon. The morphology was influenced by multiple factors including molecular design, assembly time, pH and hydrogen bond inhibitor. On the basis of experimental results, we speculated the possible assembly mechanism of Ket-L-VEVE. The π–π stacking interaction between Ket molecules could serve as an anchor, and hydrogen bonded-induced β-sheets and hydrophilic/hydrophobic balance between L-VEVE peptide play structure-directing role in forming filament-like or nanoribbon morphology. This work provides a new sight to rationally design and precisely control the nanostructure of PDCs based on aromatic fragment.

scholarly journals Peptides as a platform for targeted therapeutics for cancer: peptide–drug conjugates (PDCs)

2021 ◽  
Author(s):  
Bethany M. Cooper ◽  
Jessica Iegre ◽  
Daniel H. O' Donovan ◽  
Maria Ölwegård Halvarsson ◽  
David R. Spring
Keyword(s):  
Drug Discovery ◽  
Peptide Drug ◽  
Targeted Therapeutics ◽  
Drug Conjugates ◽  
Peptide Drug Conjugates

A tutorial review showcasing how peptide–drug conjugates can offer the versatility needed for a successful drug discovery approach, their problems and future opportunities.

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