Tuning the Properties of Penetrating Peptides by Oxime Conjugation

The cell membrane regulates the exchange of molecules and information with the external environment. However, this control barrier hinders the delivery of exogenous bioactive molecules that can be applied to correct cellular malfunctions. Therefore, the traffic of macromolecules across the cell membrane represents a great challenge for the development of the next generation of therapies and diagnostic methods. Cell‐penetrating peptides are short peptide sequences capable of delivering a broad range of biomacromolecules across the cellular membrane. However, penetrating peptides still suffer from limitations, mainly related to their lack of specificity and potential toxicity. Glycosylation has emerged as a potential promising strategy for the biological improvement of synthetic materials. In this work we have developed a new convergent strategy for the synthesis of penetrating peptides functionalized with glycan residues by an oxime bond connection. The uptake efficiency and intracellular distribution of these glycopeptides have been systematically characterized by means of flow cytometry and confocal microscopy and in zebrafish animal models. The incorporation of these glycan residues into the peptide structure influenced the internalization efficiency and cellular toxicity of the resulting glycopeptide hybrids in the different cell lines tested. The results reported herein highlight the potential of the glycosylation of penetrating peptides to modulate their activity.

show abstract

Glycosylated Cell‐Penetrating Peptides (GCPPs)

Gallego

Rioboo

Reina

et al. 2019

ChemBioChem

Self Cite

View full text Add to dashboard Cite

show abstract

Supramolecular Recognition and Selective Protein Uptake by Peptide Hybrids

Juanes

Lostalé‐Seijo

Granja

et al. 2018

Chemistry A European J

Self Cite

View full text Add to dashboard Cite

The intracellular transport of exogenous proteins has emerged as one of the most promising methodologies for biotechnology and chemical biology. Currently, protein delivery is mainly achieved by liposome encapsulation, translational fusion, and ionic/hydrophobic non-covalent aggregation with transporting molecular vehicles. This work introduces the concept of supramolecular recognition and selective transport of proteins by peptide hybrid materials. A helical amphiphilic cationic peptide that bears two orthogonal alkoxyamines for the precise anchoring of protein ligands has been designed. After the attachment of these protein ligands, the peptide showed a high binding affinity for its target protein (i.e., mannose/Concanavalin A, Biotin/Streptavidin). The resulting peptide/protein hybrids were taken up by human cells such as HeLa and HepG2. The concept described in this manuscript could potentially be adapted, through the appropriate choice of ligands, to the transport of other proteins with suitable supramolecular binding motifs.

show abstract

Different-Length Hydrazone Activated Polymers for Plasmid DNA Condensation and Cellular Transfection

et al. 2018

Self Cite

View full text Add to dashboard Cite

The recent advances in genetic engineering demand the development of conceptually new methods to prepare and identify efficient vectors for the intracellular delivery of different nucleotide payloads ranging from short single-stranded oligonucleotides to larger plasmid double-stranded circular DNAs. Although many challenges still have to be overcome, polymers hold great potential for intracellular nucleotide delivery and gene therapy. We here develop and apply the postpolymerization modification of polyhydrazide scaffolds, with different degree of polymerization, for the preparation of amphiphilic polymeric vehicles for the intracellular delivery of a circular plasmid DNA. The hydrazone formation reactions with a mixture of cationic and hydrophobic aldehydes proceed in physiologically compatible aqueous conditions, and the resulting amphiphilic polyhydrazones are directly combined with the biological cargo without any purification step. This methodology allowed the preparation of stable polyplexes with a suitable size and zeta potential to achieve an efficient encapsulation and intracellular delivery of the DNA cargo. Simple formulations that performed with efficiencies and cell viabilities comparable to the current gold standard were identified. Furthermore, the internalization mechanism was studied via internalization experiments in the presence of endocytic inhibitors and fluorescence microscopy. The results reported here confirmed that the polyhydrazone functionalization is a suitable strategy for the screening and identification of customized polymeric vehicles for the delivery of different nucleotide cargos.

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

customersupport@researchsolutions.com

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

Tuning the Properties of Penetrating Peptides by Oxime Conjugation

Cited by 3 publications

References 31 publications

Glycosylated Cell‐Penetrating Peptides (GCPPs)

Glycosylated Cell‐Penetrating Peptides (GCPPs)

Supramolecular Recognition and Selective Protein Uptake by Peptide Hybrids

Different-Length Hydrazone Activated Polymers for Plasmid DNA Condensation and Cellular Transfection

Contact Info

Product

Resources

About