Improved Prediction of Stabilizing Mutations in Proteins by Incorporation of Mutational Effects on Ligand Binding DOI

Srivarshini Ganesan,

Nidhi Mittal,

Akash Bhat

et al.

Proteins Structure Function and Bioinformatics, Journal Year: 2024, Volume and Issue: 93(1), P. 384 - 395

Published: Aug. 21, 2024

While many computational methods accurately predict destabilizing mutations, identifying stabilizing mutations has remained a challenge, because of their relative rarity. We tested ΔΔG

Language: Английский

Biologics, theranostics, and personalized medicine in drug delivery systems DOI Creative Commons
Matteo Puccetti, Marilena Pariano, Aurélie Schoubben

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: 201, P. 107086 - 107086

Published: Jan. 29, 2024

The progress in human disease treatment can be greatly advanced through the implementation of nanomedicine. This approach involves targeted and cell-specific therapy, controlled drug release, personalized dosage forms, wearable delivery, companion diagnostics. By integrating cutting-edge technologies with delivery systems, greater precision achieved at tissue cellular levels use stimuli-responsive nanoparticles, development electrochemical sensor systems. targeting – by virtue nanotechnology allows for therapy to directed specifically affected tissues while reducing side effects on healthy tissues. As such, nanomedicine has potential transform conditions such as cancer, genetic diseases, chronic illnesses facilitating precise delivery. Additionally, forms devices offer ability tailor unique needs each patient, thereby increasing therapeutic effectiveness compliance. Companion diagnostics further enable efficient monitoring response, enabling customized adjustments plan. question whether all approaches outlined here are viable alternatives current treatments is also discussed. In general, application field biomedicine may provide a strong alternative existing several reasons. this review, we aim present evidence that, although early stages, fully merging technology innovative shows promise successful across various areas, including cancer or diseases.

Language: Английский

Citations

67

Exploring Protein-Based Carriers in Drug Delivery: A Review DOI Creative Commons

Claudia Ferraro,

Marco Dattilo, Francesco Patitucci

et al.

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(9), P. 1172 - 1172

Published: Sept. 5, 2024

Drug delivery systems (DDSs) represent an emerging focus for many researchers and they are becoming progressively crucial in the development of new treatments. Great attention is given to all challenges that a drug has overcome during its journey across barriers tissues pharmacokinetics modulations needed order reach targeting sites. The goal these pathways drugs controlled way, optimizing their bioavailability minimizing side effects. Recent innovations DDSs include various nanotechnology-based approaches, such as nanoparticles, nanofibers micelles, which provide effective targeted sustained release therapeutics. In this context, protein-based gaining significant pharmaceutical field due potential revolutionize efficient delivery. As natural biomolecules, proteins offer distinct advantages, including safety, biocompatibility biodegradability, making them fascinating alternative synthetic polymers. Moreover, carriers, those derived from gelatin, albumin, collagen, gliadin silk proteins, demonstrate exceptional stability under physiological conditions, allow release, enhancing therapeutic efficacy. This review provides comprehensive overview current trends, challenges, future perspectives delivery, focusing on types adopted techniques being developed enhance functionality terms affinity capabilities, underscoring significantly impact modern

Language: Английский

Citations

5

Strategies for Non-Covalent Attachment of Antibodies to PEGylated Nanoparticles for Targeted Drug Delivery DOI Creative Commons
Kai‐Wen Ho,

Yen-Ling Liu,

Tzu‐Yi Liao

et al.

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 10045 - 10064

Published: Oct. 1, 2024

Polyethylene glycol (PEG)-modified nanoparticles (NPs) often struggle with reduced effectiveness against metastasis and liquid tumors due to limited tumor cell uptake therapeutic efficacy. To address this, actively targeted liposomes enhanced selectivity internalization are being developed improve treatment outcomes. Using bi-functional proteins functionalize PEGylated NPs enhance drug delivery through non-covalent attachment methods has emerged as a promising approach. Among these, the one-step two-step targeting strategies stand out for their simplicity, efficiency, versatility. The strategy integrates streptavidin-tagged antibodies or bispecific (bsAbs: PEG/DIG × marker) directly into NPs. This method uses natural interactions between PEG stable, specific binding, allowing modification of biotin/Fc-binding molecules like protein A, G, anti-Fc peptide. Simply mixing bsAbs improves internalization. involves first accumulating (PEG/biotin on surface, triggering an initial attack via antibody-dependent complement-dependent cytotoxicity. These then capture NPs, initiating second wave Both aim capabilities by enabling recognition binding disease-specific markers receptors. review provides potential pathways accelerating clinical translation in development nanomedicine.

Language: Английский

Citations

4

AggNet: Advancing protein aggregation analysis through deep learning and protein language model DOI Open Access
Wenjia He,

Xiaopeng Xu,

Haoyang Li

et al.

Protein Science, Journal Year: 2025, Volume and Issue: 34(2)

Published: Jan. 22, 2025

Abstract Protein aggregation is critical to various biological and pathological processes. Besides, it also an important property in biotherapeutic development. However, experimental methods profile protein are costly labor‐intensive, driving the need for more efficient computational alternatives. In this study, we introduce “AggNet,” a novel deep learning framework based on language model ESM2 AlphaFold2, which utilizes physicochemical, evolutionary, structural information discriminate amyloid non‐amyloid peptides identify aggregation‐prone regions (APRs) diverse proteins. Benchmark comparisons show that AggNet outperforms existing achieves state‐of‐the‐art performance prediction. Also, predictive ability of stable across proteins with different secondary structures. Feature analysis visualizations prove effectively captures peptides' physicochemical properties effectively, thereby offering enhanced interpretability. Further validation through case study MEDI1912 confirms AggNet's practical utility analyzing guiding mutation mitigation. This enhances tools predicting highlights potential engineering. Finally, improve accessibility AggNet, source code can be accessed at: https://github.com/Hill-Wenka/AggNet .

Language: Английский

Citations

0

Modern Approaches to Protein Constructions: A Comprehensive Review of Computational Tools and Databases for De Novo Protein Design and Engineering DOI Creative Commons

Md. Mojnu Mia,

Habiba Sultana, Md. Al Amin

et al.

Engineering Reports, Journal Year: 2025, Volume and Issue: 7(2)

Published: Feb. 1, 2025

ABSTRACT The field of protein engineering has witnessed transformative advancements, with computational tools and databases driving novel innovations in de novo design. This review consolidates critiques a comprehensive range modern resources, offering unique focus on their applications across diverse domains, including stability prediction, posttranslational modification analysis, mutation effect evaluation. Key contributions include detailed examination integrating machine learning artificial intelligence to enhance predictive accuracy streamline workflows. By highlighting underexplored methodologies, such as advanced protein–ligand interaction predictors neural network–based assessment models, this study establishes itself reference for researchers aiming develop tailored proteins therapeutic, industrial, biomedical applications.

Language: Английский

Citations

0

Pre-Concentration Freezing Alters the Composition of Mesenchymal Stem/Stromal Cell-Conditioned Medium DOI Creative Commons
Francesca Cadelano, Chiara Giannasi, Alice Gualerzi

et al.

Biology, Journal Year: 2025, Volume and Issue: 14(2), P. 181 - 181

Published: Feb. 10, 2025

Batch-to-batch reproducibility and robust quality assessment are crucial for producing cell-free biologics, such as conditioned medium (CM) derived from mesenchymal stem/stromal cells (MSCs). This study investigated the effects of freezing CM at -80 °C prior to concentration, a step that could occur in large scale pipelines, compared freshly processed CM. Quality included total protein quantification; extracellular vesicle evaluation using nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), cytofluorimetry; biochemical Raman spectroscopy. The process resulted 34% reduction content, confirmed selected bioactive mediators, significant depletion specific particle types, particularly larger ones. Interestingly, concentration polydispersity remained stable. Alterations spectra highlighted changes protein, lipid, nucleic acid content. These findings demonstrate even routine steps like can alter composition, likely due temperature-induced structural biological molecules. Careful consideration pre- intra-processing handling temperatures is critical preserving integrity ensuring consistent quality. emphasizes importance refining manufacturing protocols production biologics.

Language: Английский

Citations

0

Study on the development of nanoparticles based on levan for oral insulin delivery DOI
Desy Kurniawati, Neng Fisheri Kurniati, Enny Ratnaningsih

et al.

Biomedical Materials, Journal Year: 2025, Volume and Issue: 20(2), P. 025028 - 025028

Published: Feb. 20, 2025

Abstract Oral insulin administration has gained attention as a promising alternative to injections. However, its effectiveness is hindered by the major challenge of degradation gastric acid. Biopolymer-based nanocarriers have been explored solution address this challenge. This study examines levan, biopolymer derived from Bacillus licheniformis BK1, for viability nanocarrier insulin. Levan was modified through acetylation, and both levan (I-Lv) acetylated (I-ALv) form were utilized carriers in nanoparticles (NPs) delivery system. The resulting NPs spherical, with diameters ranging 250 500 nm encapsulation efficiencies 78.64% 88.30%, respectively. release I-Lv simulated fluid exhibited burst pattern that more rapid than I-ALv. To further evaluate, conformational stability analyzed measuring transition enthalpy secondary tertiary structures. structure determined alpha-helix content using circular dichroism, while evaluated via fluorescence intensity tryptophan residues. result revealed I-ALv enhanced compared free-state (FS) NP, enthalpies 0.91 ± 0.62 4.42 0.46 kcal mol −1 structures, Moreover, preliminary vivo studies had significant impact FS I-Lv, demonstrating reduction blood glucose levels. These findings highlight potential candidate antidiabetic therapy an efficient oral

Language: Английский

Citations

0

Citrate-Assisted Regulation of Protein Stability and Secretability from Synthetic Amyloids DOI
Hèctor López‐Laguna, Marianna Teixeira de Pinho Favaro,

Sara Chellou-Bakkali

et al.

ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

The mammalian endocrine system uses functional amyloids as dynamic depots to store and release protein hormones into the bloodstream. Such depots, acting secretory granules within microscale, are formed in specialized cells by coordination between ionic, divalent form of zinc (Zn2+) imidazole ring from accessible His residues. reversibility such cross-linking events allows for monomeric or oligomeric forms biological activity. In vitro, mimicking a natural process, synthetic amyloidal with properties can be fabricated using selected therapeutic proteins building blocks. Then, these microparticles act delivery systems endocrine-like, sustained release, proven applicability vaccinology, cancer therapy, regenerative medicine, antimicrobial agents. While temporal profile which is leaked material might highly relevant clinically oriented applications, fine control parameters remains unclear. We have explored here how kinetics regulated intervening storage formulation granules, through concentration citrate not only buffer component stabilizer but also chelating agent. citrate-assisted, time-prolonged regulatable proteins, their form, opens spectrum possibilities adjust preparation specific clinical needs.

Language: Английский

Citations

0

Fabricating N-Cadherin Mimetic Peptide-Based Diverse Self-Assembled Hydrogels in the Presence of Biologically Relevant Cations DOI
Sweta Mohanty, Sangita Roy

Biomacromolecules, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

N-cadherin, a crucial extracellular matrix protein, is in mediating cellular interactions and promoting cell migration. Herein, we have attempted to create N-cadherin mimetic peptide (NcMP) hydrogel scaffolds by incorporating cations as the external stimulus suitable interface for favorable interactions. Inspired Hofmeister series, selected four biologically significant cations, classified kosmotropes chaotropes, varied their concentrations investigate how increasing ionic strength affects self-assembly of NcMP. Interestingly, incorporation these ions greatly influenced self-assembling propensity Fmoc-HAVDI hydrogel, which resulted diverse structural mechanical properties. Such physical properties led differential responses. Thus, were able access biological single gelator molecule simply changing nature concentration relevant cations. We anticipate that systems hold great potential various biomedical applications.

Language: Английский

Citations

0

Advancing Cu/Zn Superoxide Dismutase (SOD1) production in Pichia pastoris : challenges, strategies, current research status, and future directions DOI

Abdulqader Al‐Adeeb,

Sahibzada Muhammad Aqeel,

Hend Al-Jaberi

et al.

Preparative Biochemistry & Biotechnology, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 21

Published: March 27, 2025

Cu/Zn Superoxide Dismutase (SOD1) plays a critical role in alleviating oxidative stress by catalyzing the conversion of superoxide radicals into oxygen and hydrogen peroxide. This review presents an in-depth analysis challenges strategies involved optimizing SOD1 production, with focus on Pichia pastoris as expression system. Key approaches such strategic selection vectors, codon optimization, fine-tuning fermentation parameters to maximize yield are thoroughly explored. Advances protein engineering, co-expression molecular chaperones, use stabilizers additives also examined for their improving stability functionality. The highlights significant biomedical industrial applications overexpressed thermostable SOD1, uncovering novel opportunities therapeutic interventions biotechnological innovations. Additionally, emerging technologies omics-based approaches, advanced engineering tools, alternative host systems discussed, offering new avenues future research. comprehensive underscores transformative potential positioning it at forefront scientific technological advancements.

Language: Английский

Citations

0