Deciphering the Role of π-Interactions in Polyelectrolyte Complexes Using Rationally Designed Peptides

Tabandeh, Sara; Lemus, Cristina Elisabeth; Leon, Lorraine

doi:10.3390/polym13132074

Cited by 7 publications

(10 citation statements)

References 77 publications

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“…Additionally, MB having three aromatic rings is more hydrophilic than DOX with anthraquinone rings. Moreover, our previous study confirmed that the contribution of electrostatic interactions, pi‐interactions, and hydrophobic forces drive MB encapsulation within the complex phase, where higher charge density sequence pairs with phenylalanine, p(kKf)+p(eEf), showed almost complete encapsulation [45] . Here, the most hydrophobic sequence pair with highest charge density, p(kKl)+p(eEl), had the highest encapsulation efficiency and highest retention within the complex phase.…”

Section: Discussionsupporting

confidence: 65%

“…Moreover, our previous study confirmed that the contribution of electrostatic interactions, pi-interactions, and hydrophobic forces drive MB encapsulation within the complex phase, where higher charge density sequence pairs with phenylalanine, p(kKf) + p(eEf), showed almost complete encapsulation. [45] Here, the most hydrophobic sequence pair with highest charge density, p(kKl) + p(eEl), had the highest encapsulation efficiency and highest retention within the complex phase. Optical microscopy and deconvolution of the FTIR spectra showed that DOX does not affect the phase behavior of complexes, while MB induces hydrogen bonding in p(kKl) + p(eEl), causing a transition from liquid coacervates to solid precipitates.…”

Section: Discussionmentioning

confidence: 87%

Section: Resultsmentioning

confidence: 96%

“…We previously reported an almost complete encapsulation of MB within a sequence pair with a similar design to the second generation, p(kKx) + p(eEx), and an aromatic residue, phenylalanine, in the x position. [45] We attributed the significantly higher encapsulation efficiency of p(kKf) + p(eEf) (more than 99 %) to a cooperative effect of electrostatic and piinteractions. Furthermore, in a study by our group on PEC based micelles, despite a primarily ionic interaction with the polyanion, MB was not encapsulated by the micelle and showed a counterion-like behavior.…”

Section: Encapsulation Of Methylene Blue (Mb)mentioning

confidence: 85%

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Drug Encapsulation via Peptide‐Based Polyelectrolyte Complexes

Tabandeh,

Ateeq,

Leon

2023

ChemBioChem

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Peptide‐based polyelectrolyte complexes are biocompatible materials that can encapsulate molecules with different polarities due to their ability to be precisely designed. Here we use UV‐Vis spectroscopy, fluorescence microscopy, and infrared spectroscopy to investigate the encapsulation of model drugs, doxorubicin (DOX) and methylene blue (MB) using a series of rationally designed polypeptides. For both drugs, we find an overall higher encapsulation efficiency with sequences that have higher charge density, highlighting the importance of ionic interactions between the small molecules and the peptides. However, comparing molecules with the same charge density, illustrated that the most hydrophobic sequence pairs had the highest encapsulation of both DOX and MB molecules. The phase behavior and stability of DOX‐containing complexes did not change compared to the complexes without drugs. However, MB encapsulation caused changes in the stabilities of the complexes. The sequence pair with the highest charge density and hydrophobicity had the most dramatic increase in stability, which coincided with a phase change from liquid to solid. This study illustrates how multiple types of molecular interactions are required for efficient encapsulation of poorly soluble drugs and provides insights into the molecular design of delivery carriers.

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Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 87%

Section: Resultsmentioning

confidence: 96%

Section: Encapsulation Of Methylene Blue (Mb)mentioning

confidence: 85%

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Drug Encapsulation via Peptide‐Based Polyelectrolyte Complexes

Tabandeh,

Ateeq,

Leon

2023

ChemBioChem

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“…Figure S2 suppressed at concentration values higher than this critical concentration. Leon et al demonstrated that hydrophobic interactions were dominant for phenylalanine aggregation at high salt concentrations (> 250 mM), while π-interactions and electrostatic interactions such as charge-charge interactions played an important role in the aggregation at low salt concentrations (≤ 250 mM) [44]. These previous reports indicated that polymer aggregation occurs at a critical concentration of the solution, which is proposed to be C NaCl = 150 mM for the J-aggregation of TPPS in the present study.…”

Section: J-aggregation Of Tpps In the Dilute Solutionmentioning

confidence: 99%

J-aggregation of 5, 10, 15, 20-tetraphenyl-21H, 23H-porphinetetrasulfonic acid in a molecular crowding environment simulated using dextran

Miyagawa

Nakatani

2022

ANAL. SCI.

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In a molecular crowding environment, different thermodynamics is often observed in a dilute solution. One such example is the promotion of the formation of amyloids, which are causal agents of Alzheimer's disease. Although a considerable number of molecular crowding studies have been reported, its effect remains unclear. In this study, we investigated a J-aggregation of a porphyrin derivative, 5, 10, 15, 20-tetraphenyl-21H,23H-porphinetetrasulfonic acid (TPPS), in a molecular crowding environment simulated by dextran (Dex) in HClO 4 , HCl, and NaCl solutions. The changes in the number of monomers in the J-aggregate (n) with the concentration of Dex (C Dex ) depended on the type of solution. No change in n was observed in the NaCl solution, which indicated that the Dex solution did not affect the J-aggregation because of the ionic strength effect. In the HCl solution, the aggregation behavior changed with the pH. Further, at a low pH, the electrostatic interactions promoted J-aggregation by the volume exclusion of Dex, while the aggregation was suppressed at a high pH owing to steric hindrance. A different aggregation mechanism, involving the hydrogen bonding between NH in the center of the TPPS macrocyclic frame and the SO 3 H and ClO 4 − functional groups, was responsible for the J-aggregation in the HClO 4 solution. Moreover, the n value increased owing to the volume exclusion effect. We expect that this study will be useful for further elucidation of the molecular crowding effect.

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Self-Assembling Polypeptides in Complex Coacervation

Sathyavageeswaran,

Bonesso Sabadini,

Perry

2024

Acc. Chem. Res.

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Metrics & MoreArticle Recommendations CONSPECTUS: Intracellular compartmentalization plays a pivotal role in cellular function, with membrane-bound organelles and membrane-less biomolecular "condensates" playing key roles. These condensates, formed through liquid−liquid phase separation (LLPS), enable selective compartmentalization without the barrier of a lipid bilayer, thereby facilitating rapid formation and dissolution in response to stimuli.Intrinsically disordered proteins (IDPs) or proteins with intrinsically disordered regions (IDRs), which are often rich in charged and polar amino acid sequences, scaffold many condensates, often in conjunction with RNA.Comprehending the impact of IDP/IDR sequences on phase separation poses a challenge due to the extensive chemical diversity resulting from the myriad amino acids and post-translational modifications.To tackle this hurdle, one approach has been to investigate LLPS in simplified polypeptide systems, which offer a narrower scope within the chemical space for exploration. This strategy is supported by studies that have demonstrated how IDP function can largely be understood based on general chemical features, such as clusters or patterns of charged amino acids, rather than residue-level effects, and the ways in which these kinds of motifs give rise to an ensemble of conformations.Our laboratory has utilized complex coacervates assembled from oppositely charged polypeptides as a simplified material analogue to the complexity of liquid−liquid phase separated biological condensates. Complex coacervation is an associative LLPS that occurs due to the electrostatic complexation of oppositely charged macro-ions. This process is believed to be driven by the entropic gains resulting from the release of bound counterions and the reorganization of water upon complex formation. Apart from their direct applicability to IDPs, polypeptides also serve as excellent model polymers for investigating molecular interactions due to the wide range of available side-chain functionalities and the capacity to finely regulate their sequence, thus enabling precise control over interactions with guest molecules. Here, we discuss fundamental studies examining how charge patterning, hydrophobicity, chirality, and architecture affect the phase separation of polypeptide-based complex coacervates. These efforts have leveraged a combination of experimental and computational approaches that provide insight into molecular level interactions. We also examine how these parameters affect the ability of complex coacervates to incorporate globular proteins and viruses. These efforts couple directly with our fundamental studies into coacervate formation, as such "guest" molecules should not be considered as experiencing simple encapsulation and are instead active participants in the electrostatic assembly of coacervate materials. Interestingly, we observed trends in the incorporation of proteins and viruses into coacervates formed using different chain length polypeptides that are not well explained by...

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Deciphering the Role of π-Interactions in Polyelectrolyte Complexes Using Rationally Designed Peptides

Cited by 7 publications

References 77 publications

Drug Encapsulation via Peptide‐Based Polyelectrolyte Complexes

Drug Encapsulation via Peptide‐Based Polyelectrolyte Complexes

J-aggregation of 5, 10, 15, 20-tetraphenyl-21H, 23H-porphinetetrasulfonic acid in a molecular crowding environment simulated using dextran

Self-Assembling Polypeptides in Complex Coacervation

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