Cellular Uptake and Cytotoxicity of Drug–Peptide Conjugates Regulated by Conjugation Site

Zhang, Pengcheng; Cheetham, Andrew G.; Lock, Lye Lin; Cui, Honggang

doi:10.1021/bc300585h

Cited by 96 publications

(86 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although, cationic amino acids cannot self-assemble due to the repletion of their high charge, they are known for their cell penetrating abilities. One of the most popular examples of cell-penetrating peptides (CPPs), transactivator of transcription (TAT), has been widely used for anti-cancer drug conjugates to increase cellular uptake and intracellular retention in cervical cancer cells [86,87]. …”

Section: Peptide-peptide Interaction Driven Self-assemblymentioning

confidence: 99%

Self-assembling peptide-based building blocks in medical applications

Acar

Srivastava

Chung

et al. 2017

Advanced Drug Delivery Reviews

185

155

View full text Add to dashboard Cite

Peptides and peptide-conjugates, comprising natural and synthetic building blocks, are an increasingly popular class of biomaterials. Self-assembled nanostructures based on peptides and peptide-conjugates offer advantages such as precise selectivity and multifunctionality that can address challenges and limitations in the clinic. In this review article, we discuss recent developments in the design and self-assembly of various nanomaterials based on peptides and peptide-conjugates for medical applications, and categorize them into two themes based on the driving forces of molecular self-assembly. First, we present the self-assembled nanostructures driven by the supramolecular interactions between the peptides, with or without the presence of conjugates. The studies where nanoassembly is driven by the interactions between the conjugates of peptide-conjugates are then presented. Particular emphasis is given to in vivo studies focusing on therapeutics, diagnostics, immune modulation and regenerative medicine, and challenges and future perspective are presented.

show abstract

Section: Peptide-peptide Interaction Driven Self-assemblymentioning

confidence: 99%

Self-assembling peptide-based building blocks in medical applications

Acar

Srivastava

Chung

et al. 2017

Advanced Drug Delivery Reviews

185

155

View full text Add to dashboard Cite

show abstract

“…Furthermore, with the cargo carrying properties of CPPs, they are finding use in the delivery of cancer drugs such as doxorubicin [248,355], taxol [356], paclitaxel [357], docetaxel [358]. Using peptide conjugates for drug delivery into the cell has been a topic of interest and there are many anticancer [359], antiinflammatory [360] and neurodegenerative [361] peptide conjugate drugs that are in clinical use or under investigation. Our group has also been focusing on combining the inhibitory properties of inhibitor peptides with CPPs [362].…”

Section: Future Perspectives: Characterizing Membrane Active Peptidesmentioning

confidence: 99%

Membrane Active Peptides and Their Biophysical Characterization

Avcı

Akbulut

Özkırımlı

2018

Preprint

View full text Add to dashboard Cite

In the last 20 years, an increasing number of studies have been reported on membrane active peptides, which exert their biological activity by interacting with the cell membrane either to disrupt it and lead to cell lysis or to translocate through it to deliver cargos into the cell and reach their target. These peptides are attractive alternatives to currently used pharmaceuticals. Antimicrobial peptides (AMPs) and peptides designed for drug and gene delivery currently in the drug pipeline suggest that these membrane active peptides will soon constitute a significant percentage of the drug market. Here, we focus on two most prominent classes of membrane active peptides; AMPs and cell-penetrating peptides (CPPs). AMPs are a group of membrane active peptides that disrupt the membrane integrity or inhibit the cellular functions of bacteria, virus and fungi. CPPs are another group of membrane active peptides that mainly function as cargo-carriers even though they may also show antimicrobial activity to some extent. Biophysical techniques to understand how they interact with the membrane have shed light on the peptide-membrane interaction at various levels of detail. Structural investigation of membrane active peptides in the presence of the membrane provides important clues on the effect of the membrane environment on peptide conformations. Advances in live imaging techniques have allowed examination of peptide action at a single cell or single molecule level. In addition to these experimental biophysical techniques, molecular dynamics simulations provided clues on the peptide-lipid interactions and dynamics of the cell entry process at atomic detail. In this review, we summarize the recent advances in experimental and computational investigation of membrane active peptides with particular emphasis on two amphipathic membrane active peptides, the AMP melittin and the CPP pVEC.

show abstract

“…10 For example, the Cui laboratory has explored the pathway of DA cellular internalization. 99 With confocal microscopy, the lab has explored the pathway for free doxorubicin (DOX), as well as for DOX conjugated to the TAT peptide. As previously discussed, the TAT peptide sequence has been shown to translocate the membrane and accumulate in the cell nucleus.…”

Section: Interactions With Membranesmentioning

confidence: 99%

“…Experiments have suggested that conjugation of the TAT sequence to DOX changes the mechanism of cellular internalization from a passive mechanism to an active or endocytosis-mediated mechanism. 99 Several questions are raised by this result, such as: i) what is the change in the binding free energy of TAT with the membrane when attaching a hydrophobic drug? Additionally, ii) why does the original mechanism of cooperative pore-formation for TAT translocation become inefficient?…”

Section: Interactions With Membranesmentioning

confidence: 99%

Molecular simulations of peptide amphiphiles

et al. 2017

View full text Add to dashboard Cite

This review describes recent progress in the area of molecular simulations of peptide assemblies, including peptide-amphiphiles, and drug-amphiphiles. The ability to predict the structure and stability of peptide self-assemblies from the molecular level up is vital to the field of nanobiotechnology. Computational methods such as molecular dynamics offer the opportunity to characterize intermolecular forces between peptide-amphiphiles that are critical to the self-assembly process. Furthermore, these computational methods provide the ability to computationally probe the structure of these supramolecular assemblies at the molecular level, which is a challenge experimentally. Herein, we briefly highlight progress in the areas of all-atomistic and coarse-grained simulation studies investigating the self-assembly process of short peptides and peptide amphiphiles. We also discuss recent all-atomistic and coarse-grained simulations of the self-assembly of a drug-amphiphile into elongated filaments. Next, we discuss how these computational methods can provide further insight on the pathway of cylindrical nanofiber formation and predict their biocompatibility by studying the interaction of these peptide-amphiphile nanostructures with model cell membranes.

show abstract

Cellular Uptake and Cytotoxicity of Drug–Peptide Conjugates Regulated by Conjugation Site

Cited by 96 publications

References 67 publications

Self-assembling peptide-based building blocks in medical applications

Self-assembling peptide-based building blocks in medical applications

Membrane Active Peptides and Their Biophysical Characterization

Molecular simulations of peptide amphiphiles

Contact Info

Product

Resources

About