Stimuli-responsive peptide assemblies: Design, self-assembly, modulation, and biomedical applications

Mu, Rongqiu; Zhu, Danzhu; Abdulmalik, Sama; Wijekoon, Suranji; Wei, Gang; Kumbar, Sangamesh G.

doi:10.1016/j.bioactmat.2024.01.023

Cited by 9 publications

(6 citation statements)

References 200 publications

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“…The main strategies include the design of analogs resistant to peptide metabolism by introducing nonproteinaceous amino acids, cyclization, or peptide bond replacement. Another approach explores the concept of providing protection to the peptide by a delivery method, either based on non-oral administration, i.e., inhaled, buccal, intranasal, or transdermal, or employing molecular drug delivery systems [31,116,202]. With the opioid crisis and growing demand for pain relief, the idea of designing, adapting, and using drug delivery systems is gaining importance [203].…”

Section: Drug Delivery Systems For Antinociceptive Peptidesmentioning

confidence: 99%

Analgesic Peptides: From Natural Diversity to Rational Design

Gach-Janczak,

Biernat,

Kuczer

et al. 2024

Molecules

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Pain affects one-third of the global population and is a significant public health issue. The use of opioid drugs, which are the strongest painkillers, is associated with several side effects, such as tolerance, addiction, overdose, and even death. An increasing demand for novel, safer analgesic agents is a driving force for exploring natural sources of bioactive peptides with antinociceptive activity. Since the G protein-coupled receptors (GPCRs) play a crucial role in pain modulation, the discovery of new peptide ligands for GPCRs is a significant challenge for novel drug development. The aim of this review is to present peptides of human and animal origin with antinociceptive potential and to show the possibilities of their modification, as well as the design of novel structures. The study presents the current knowledge on structure-activity relationship in the design of peptide-based biomimetic compounds, the modification strategies directed at increasing the antinociceptive activity, and improvement of metabolic stability and pharmacodynamic profile. The procedures employed in prolonged drug delivery of emerging compounds are also discussed. The work summarizes the conditions leading to the development of potential morphine replacements.

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Section: Drug Delivery Systems For Antinociceptive Peptidesmentioning

confidence: 99%

Analgesic Peptides: From Natural Diversity to Rational Design

Gach-Janczak,

Biernat,

Kuczer

et al. 2024

Molecules

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“…The redox reactivity of Met has inspired the design of biomaterials responsive to ROS. − Redox-responsive polypeptides based on Met have been designed to control properties such as the thermal phase transition upon oxidation . In addition, self-assembling peptides − have been recognized as highly important components for designing biomaterials. Alternating hydrophilic and hydrophobic amino acid sequences is often used to design hydrogel-forming amphiphilic peptides that aggregate through hydrophobic interactions and β-sheet formation.…”

Section: Introductionmentioning

confidence: 99%

ROS-Responsive Methionine-Containing Amphiphilic Peptides Impart Enzyme-Triggered Phase Transition and Antioxidant Cell Protection

Hara,

Yoshizawa,

Yaguchi

et al. 2024

Biomacromolecules

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Reactive oxygen species (ROS) are produced by cellular activities, such as metabolism and immune response, and play important roles in cell signaling and homeostasis. However, overproduced ROS causes irreversible damage to nucleic acids and membrane lipids, supporting genetic mutations and enhancing the effects of aging. Cells defend themselves against ROS using antioxidant systems based on redox-active sulfur and transition metals. Inspired by such biological redox-responsive systems, we developed methionine-containing self-assembling peptides. The Met-containing peptides formed hydrogels that underwent a gel-to-sol phase transition upon oxidation by H2O2, and the sensitivity of the peptides to the oxidant increased as the number of Met residues increased. The peptide containing three Met residues, the largest number of Met residues in our series of designed peptides, showed the highest sensitivity to oxidation and detoxification to protect cells from ROS damage. In addition, this peptide underwent a phase transition in response to H2O2 produced by an oxidizing enzyme. This study demonstrates the design of a supramolecular biomaterial that is responsive to enzymatically generated ROS and can protect cells against oxidative stress.

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“…In the drug development process, many candidates fail to pass preclinical and clinical studies due to high cytotoxicity, low targeting efficiency and adverse pharmacokinetic effects. − To improve drug efficacy and reduce side effects, novel drug delivery systems (DDSs) have been developed for small molecules, peptides and proteins. − Among them, peptide-based DDSs have shown great clinical potential owing to their good biocompatibility, low toxicity, and high biological activity. , For example, peptide-drug conjugates enable precise molecular-targeted therapy at the cellular level and have been used clinically as diagnostic agents and anticancer drugs. , Peptide-based hydrogel DDS exhibits good biodegradability so that can be used for intratumoral, subcutaneous and ocular drug delivery. − Peptides capable of penetrating cell membranes, when combined with tumor-targeting peptides, can selectively transport toxins or prodrug molecules to specific tissues and cells, thereby enhancing therapeutic efficacy. − Moreover, peptides can be used for the treatment of various diseases through self-assembly − or the formation of nanoparticles . Despite the significant advantages of peptides in drug delivery, poor cell membrane permeability severely hinders the development of peptide-delivered drugs .…”

Section: Introductionmentioning

confidence: 99%

Predicting Peptide Permeability Across Diverse Barriers: A Systematic Investigation

Tan,

Liu,

Fang

et al. 2024

Mol. Pharmaceutics

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Peptide-based therapeutics hold immense promise for the treatment of various diseases. However, their effectiveness is often hampered by poor cell membrane permeability, hindering targeted intracellular delivery and oral drug development. This study addressed this challenge by introducing a novel graph neural network (GNN) framework and advanced machine learning algorithms to build predictive models for peptide permeability. Our models offer systematic evaluation across diverse peptides (natural, modified, linear and cyclic) and cell lines [Caco-2, Ralph Russ canine kidney (RRCK) and parallel artificial membrane permeability assay (PAMPA)]. The predictive models for linear and cyclic peptides in Caco-2 and RRCK cell lines were constructed for the first time, with an impressive coefficient of determination (R 2 ) of 0.708, 0.484, 0.553, and 0.528 in the test set, respectively. Notably, the GNN framework behaved better in permeability prediction with larger data sets and improved the accuracy of cyclic peptide prediction in the PAMPA cell line. The R 2 increased by about 0.32 compared with the reported models. Furthermore, the important molecular structural features that contribute to good permeability were interpreted; the influence of cell lines, peptide modification, and cyclization on permeability were successfully revealed. To facilitate broader use, we deployed these models on the user-friendly KNIME platform (https://github.com/ifyoungnet/PharmPapp). This work provides a rapid and reliable strategy for systematically assessing peptide permeability, aiding researchers in drug delivery optimization, peptide preselection during drug discovery, and potentially the design of targeted peptide-based materials.

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Stimuli-responsive peptide assemblies: Design, self-assembly, modulation, and biomedical applications

Cited by 9 publications

References 200 publications

Analgesic Peptides: From Natural Diversity to Rational Design

Analgesic Peptides: From Natural Diversity to Rational Design

ROS-Responsive Methionine-Containing Amphiphilic Peptides Impart Enzyme-Triggered Phase Transition and Antioxidant Cell Protection

Predicting Peptide Permeability Across Diverse Barriers: A Systematic Investigation

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