Role of Charge Heterogeneity on Physical Stability of Monoclonal Antibody Biotherapeutic Products.

PURPOSE: Chemical modifications in monoclonal antibodies can change hydrophobicity, charge heterogeneity as well as conformation, which eventually can impact their physical stability. In this study, the effect of the individual charge variants on physical stability and aggregation propensity in two different buffer conditions used during downstream purification was investigated. METHODS: The charge variants were separated using semi-preparative cation exchange chromatography and buffer exchanged in the two buffers with pH 6.0 and 3.8. Subsequently each variant was analysed for size heterogeneity using size exclusion chromatography and dynamic light scattering, conformational stability, colloidal stability, and aggregation behaviour under accelerated stability conditions. RESULTS: Size variants in each charge variant were similar in both pH conditions when analyzed without extended storage. However, conformational stability was lower at pH 3.8 than pH 6.0. All charge variants showed similar apparent melting temperature at pH 6.0. In contrast, at pH 3.8 variants A3, A5, B2, B3 and B4 display lower Tm, suggesting reduced conformational stability. Further, A2, A3 and A5 exhibit reduced colloidal stability at pH 3.8. In general, acidic variants are more prone to aggregation than basic variants. CONCLUSION: Typical industry practice today is to examine in-process intermediate stability with acidic species and basic species taken as a single category each. We suggest that perhaps stability evaluation needs to be performed at specie level as different acidic or basic species have different stability and this knowledge can be used for clever designing of the downstream process to achieve a stable product.

Improving the stability of insulin through effective chemical modifications: A Comprehensive review.

Insulin, an essential peptide hormone, conjointly regulates blood glucose levels by its receptor and it is used as vital drug to treat diabetes. This therapeutic hormone may undergo different chemical modifications during industrial processes, pharmaceutical formulation, and through its endogenous storage in the pancreatic ß-cells. Insulin is highly sensitive to environmental stresses and readily undergoes structural changes, being also able to unfold and aggregate in physiological conditions. Even; small changes altering the structural integrity of insulin may have significant impacts on its biological efficacy to its physiological and pharmacological activities. Insulin analogs have been engineered to achieve modified properties, such as improved stability, solubility, and pharmacokinetics, while preserving the molecular pharmacology of insulin. The casually or purposively strategies of chemical modifications of insulin occurred to improve its therapeutic and pharmaceutical properties. Knowing the effects of chemical modification, formation of aggregates, and nanoparticles on protein can be a new look at the production of protein analogues drugs and its application in living system. The project focused on effects of chemical modifications and nanoparticles on the structure, stability, aggregation and their results in effective drug delivery system, biological activity, and pharmacological properties of insulin. The future challenge in biotechnology and pharmacokinetic arises from the complexity of biopharmaceuticals, which are often molecular structures that require formulation and delivery strategies to ensure their efficacy and safety.

Effects of Chemical Modification on the Structure and Biological Activities of Polysaccharides Extracted from Inonotus Obliquus by Microwave.

A novel polysaccharide, Inonotus obliquus polysaccharide (IOP), was extracted using a microwave extraction method and subsequently subjected to modifications through sulfation, carboxymethylation, phosphorylation, and acetylation. Its physical and chemical properties were analyzed using various chemical techniques, including high-pressure liquid chromatography, ultraviolet light, Fourier-transform infrared spectroscopy, X-ray diffraction, Congo red test, and scanning electron microscopy. The antioxidant capacity was assessed using DPPH, ABTS, and hydroxyl radical assays, as well as by measuring the reducing power. Additionally, hypoglycemic activity was evaluated through α-glucosidase and α-amylase assays. The results indicated that the chemical modifications effectively altered the physical and chemical properties, as well as the biological activities of IOP. Compared to the unmodified IOP, the derivatives exhibited reduced sugar content, uronic acid content, and molecular weight, while demonstrating varying levels of antioxidant and hypoglycemic capabilities. Notably, the carboxymethylated IOP (IOP-C) displayed lower molecular weight, higher ABTS free radical scavenging rate, greater reducing ability, and increased α-amylase inhibition rate. Therefore, IOP-C shows promise as a potential edible antioxidant and hypoglycemic agent.

Enhancement of Filtration Performance Characteristic of Glass Fiber-Based Filter Media, Part 2: Chemical Modification with Surface-Active Treatment.

Standard glass fiber filter media were chemically modified with suitably chosen surface-active agents. The aim of these modifications was to improve the three fundamental filtration performance characteristics, namely, to increase the separation efficiency, reduce the differential pressure (∆P) and increase the dirt holding capacity (DHC). The increase in separation efficiency was considered quantitatively in terms of changes in the work of adhesion between the contaminant and the modified media substrate derived from the contact angle measurements. The experimental confirmation of this behavior was demonstrated by an improved separation efficiency especially for particles in the smaller size ranges, well below the mean porosity of the original substrate. In addition, the effect of different surface modifications, especially those of the opposite ends of the surface energy values, has clearly manifested itself in the experimental results of separation efficiency derived from the multipass evaluations. Collectively, the obtained contact angle (surface energy) and separation efficiency results are strongly indicative of a wide range of filtration performance enhancements that can be achieved through suitably chosen surface-active modification of standard substrate materials.

Structure Characterization and Dye Adsorption Properties of Modified Fiber from Wheat Bran.

The fibers from four wheat varieties (FT, XW 26, XW 45, and KW 1701) were selected and chemically modified with NaOH, epichlorohydrin, and dimethylamine to improve the adsorption capacity for anionic dye. The structure of the fibers with or without modification was characterized by scanning electron microscope (SEM), X-ray diffraction (XRD), and Fourier-transform infrared (FTIR) spectrometry. The modified products were studied from the aspects of adsorption capacities, adsorption kinetics, and thermodynamics to provide a reference for the utilization of wheat bran. By SEM, more porous and irregular structures were found on the modified fibers. The XRD results showed that the crystals from the original fibers were destroyed in the modification process. The changes in fibers' infrared spectra before and after modification suggested that quaternary ammonium salts were probably formed in the modification process. The maximum adsorption capacity of wheat bran fibers for Congo red within 120 min was 20 mg/g for the unmodified fiber (XW 26) and 93.46 mg/g for the modified one (XW 45). The adsorption kinetics of Congo red by modified wheat bran fiber was in accord with the pseudo-second-order kinetic model at 40 °C, 50 °C, and 60 °C, indicating that the adsorption process might be mainly dominated by chemisorption. The adsorption was more consistent with the Langmuir isothermal adsorption model, implying that this process was monolayer adsorption. The thermodynamic parameters suggested that the adsorption occurred spontaneously, and the temperature increase was favorable to the adsorption. As mentioned above, this study proved that the wheat bran fiber could possess good adsorption capacities for anion dye after chemical modification.

The Influence of Environmental Factors on the Degradation of PLA/Diatomaceous Earth Composites.

In the present study, tests were carried out on composite samples on a polylactide matrix containing 25% by weight of mineral filler in the form of diatomaceous earth, base, and silanized with GPTMOS (3-glycidoxypropyltrimethoxysilane), OTES (n-octyltriethoxysilane), and MTMOS (methyltrimethoxysilane) silanes. The addition of two types of waxes, synthetic polyamide wax and natural beeswax, were used as a factor to increase the rheological properties of the composites. The obtained samples were characterized in terms of the effect of filler silanization on the degradation rate of the composites. The tests were conducted under different conditioning conditions, i.e., after exposure to strong UV radiation for 250 and 500 h, and under natural sunlight for 21 days. The conditioning carried out under natural conditions showed that the modified samples exhibit up to twice the degradation rate of pure polylactide. The addition of synthetic wax to the composites increases the tendency to agglomerate diatomaceous earth, while natural wax has a positive effect on filler dispersion. For composites modified with GPTMOS and OTES silanes, it was noted that the addition of natural wax inhibited the degree of surface degradation, compared to the addition of synthetic wax, while the addition of MTMOS silane caused the opposite effect and samples with natural wax degraded more strongly. It was shown that, despite the high degree of surface degradation, the process does not occur significantly deep into the composite and stops at a certain depth.

Medicinal Chemistry of Antisense Oligonucleotides for Therapeutic Use in SARS-CoV-2: Design Strategies and Challenges for Targeted Delivery.

BACKGROUND: The evolution of novel Severe Acute Respiratory Syndrome-related Coronavirus 2 (SARS-CoV-2) strains with greater degrees of infectivity, resistance to vaccine-induced acquired immunity, and more severe morbidity have contributed to the recent spread of COVID-19. In light of this, novel therapeutic alternatives with improved effectiveness and fewer side effects have become a necessity. Despite many new or repurposed antiviral agents recommended for Coronavirus disease (COVID-19) therapy, this objective remains unfulfilled. Under these circumstances, the scientific community holds the significant responsibility to develop classes of novel therapeutic modalities to combat SARS-CoV-2 with the least harmful side effects. OBJECTIVE: Antisense Oligonucleotides (ASOs) are short single-stranded oligonucleotides that allow the specific targeting of RNA, leading to its degradation. They may also prevent cellular factors or machinery from binding to the target RNA. It is possible to improve the pharmacokinetics and pharmacodynamics of ASOs by chemical modification or bioconjugation, which may provide conditions for customization of a particular clinical target. This study aimed to outline the potential use of ASOs in the treatment of COVID-19 disease, along with the use of antisense stabilization and transfer methods, as well as future challenges and limitations. METHODS: We have reviewed the structure and properties of ASOs containing nucleobase, sugar, or backbone modifications, and provided an overview of the therapeutic potential, delivery challenges, and strategies of ASOs in the treatment of COVID-19. RESULTS: The first-line therapy for COVID-19-infected individuals, as well as the development of oligonucleotide-based drugs, warrants further investigation. Chemical changes in the oligonucleotide structure can affect the biological processes. These chemical alterations may lead to enhanced potency, while changing the pharmacokinetics and pharmacodynamics. CONCLUSION: ASOs can be designed to target both coding and non-coding regions of the viral genome to disrupt or completely degrade the genomic RNA and thereby eliminate SARS-CoV-2. They may be very effective in areas, where vaccine distribution is challenging, and they may be helpful for future coronavirus pandemics.

Esterification of dextran by octenyl succinic anhydride (OSA): Physicochemical characterization and functional properties assessment.

The chemical modification of biopolymers to enhance their functional properties in the food, cosmetic, and pharmaceutical industries is an area of particular interest today. In this study, different molecular weight dextrans were chemically modified for the first time with octenyl succinic anhydride (OSA). This reaction involves an esterification process wherein the hydroxy groups of dextran are partially substituted by a carbonaceous chain, imparting hydrophobic properties to dextran molecules and, consequently, an amphiphilic nature. To assess and quantify the incorporation of OSA into the dextran structure, reaction products were analysed using NMR and FTIR. Additionally, the thermal properties, the Z-potential and the foaming and emulsifying capacity of both native and modified dextrans were examined. The introduction of OSA groups to dextran molecules, with degrees of substitution between 0.028 and 0.058, increased the zeta potential and the thermal stability of the polymer. Furthermore, the chemical modification of dextran backbone with this radical conferred a hydrophobic nature to the biopolymer, which enhance its foaming and emulsifying capacity. Therefore, these results demonstrate that the incorporation of hydrophobic moieties into dextran polymers improves their functional properties and broadens their potential applications in the industry.

Ecofriendly dual-function cotton fabric with antibacterial and anti-adhesion properties based on modified natural materials.

Ecofriendly fabrics with antibacterial and anti-adhesion properties have been attracted an increasing attention in recent years. Herein, natural menthol modified polyacrylate (PMCA) antibacterial adhesion agent was synthesized by esterification and polymerisation while natural pterostilbene-grafted-chitosan (PGC) antibacterial agent was prepared through Mannich reaction. The antibacterial and anti-adhesion cotton fabric was fabricated through durable PMCA dip finishing and then layer-by-layer self-assembly of PGC. The results showed that the antibacterial adhesion rates and antibacterial rates of the dual-function cotton fabric against Staphylococcus aureus and Escherichia coli reached up to 99.9 %. Its antibacterial adhesion rates improved by 36.1 % and 40.1 % in comparison with those of cotton fabric treated by menthol alone. Meanwhile against S. aureus, the dual-function cotton fabrics improved the antibacterial rates by 56.7 % and 36.4 %, respectively, from those of chitosan- and pterostilbene-treated fabrics. Against E. coli, the improvements were 89.4 % and 24.8 %, respectively. After 20 household washings, the dual-function cotton fabric maintained >80 % of its original anti-adhesion and antibacterial rates against both species. The dual-function cotton fabric also possessed safe and excellent wearability.

Conjugating Hemoglobin and Albumin by Strain-Promoted Azide-Alkyne Cycloaddition.

A one-to-one conjugate of cross-linked human hemoglobin and human serum albumin results from a strain-promoted azide-alkyne cycloaddition (SPAAC) of the modified proteins. Additions of a strained alkyne-substituted maleimide to the Cys-34 thiol of human serum albumin and an azide-containing cross-link between the amino groups of each b-unit at Lys-82 of human hemoglobin provide sites for coupling by the SPAAC process. The coupled hemoglobin-albumin conjugate can be readily purified from the unreacted hemoglobin. The oxygen binding properties of this two-protein conjugate demonstrate an oxygen affinity and binding cooperativity suitable as an acellular oxygen carrier.

Highly enhanced chloramphenicol adsorption performance of MIL-53-NH2(Al)-derived porous carbons modified with tannic acid.

The worldwide demand for antibiotics has experienced a notable surge, propelled by the repercussions of the COVID-19 pandemic and advancements in the global healthcare sector. A prominent challenge confronting humanity is the unregulated release of antibiotic-laden wastewater into the environment, posing significant threats to public health. The adoption of affordable carbon-based adsorbents emerges as a promising strategy for mitigating the contamination of antibiotic wastewater. Here, we report the synthesis of novel porous carbons (MPC) through a direct pyrolysis of MIL-53-NH2(Al) and tannic acid (TANA) under N2 atmosphere at 800 °C for 4 h. The effect of TANA amount ratios (0%-20%, wt wt-1) on porous carbon structure and adsorption performance was investigated. Results showed that TANA modification resulted in decreased surface area (1,600 m2 g-1-949 m2 g-1) and pore volume (2.3 cm3 g-1-1.7 cm3 g-1), but supplied hydroxyl functional groups. Adsorption kinetic, intraparticle diffusion, and isotherm were examined, indicating the best fit of Elovich and Langmuir models. 10%-TANA-MPC obtained an ultrahigh adsorption capacity of 564.4 mg g-1, which was approximately 2.1 times higher than that of unmodified porous carbon. 10%-TANA-MPC could be easily recycled up to 5 times, and after reuse, this adsorbent still remained highly stable in morphology and surface area. The contribution of H bonding, pore-filling, electrostatic and π-π interactions to chloramphenicol adsorption was clarified. It is recommended that TANA-modified MIL-53-NH2(Al)-derived porous carbons act as a potential adsorbent for removal of pollutants effectively.

Chemical modification, structure elucidation and antifungal mechanism studies of a peptide extracted from garlic (Allium sativum L.).

BACKGROUND: Garlic is a promising source of antimicrobial peptide separation, and chemical modification is an effective method for activity improvement. The present study aimed to improve the antifungal activity of a peptide extracted from garlic. Chemical modifications were conducted, and the structure-activity relationship and antifungal mechanism were investigated. RESULTS: The results indicated that the cationic charge induced by Lys residue at the N-terminal was important for the antimicrobial activity, and the modified sequence exhibited significant antifungal activity with low mammalian toxicity and a low tendency of drug resistance (p < 0.05). The structure-activity relationship analysis revealed that the modified active peptide had a predominant α-helical structure and an inner cyclic correlation. Transcriptomic analysis showed that peptide KMLKKLFR (Lys-Met-Leu-Lys-Lyse-Leu-Phe-Arg) affected the rRNA processing and carbon metabolism process of Candida albicans. In addition, the membrane potential study indicated a non-membrane destruction mechanism, and molecular docking analysis and a DNA interaction assay suggested promising inner targets. CONCLUSION: The results of the present study indicate that chemical modification by amino acid substitution was effective for antimicrobial activity improvement. The present study would benefit future antimicrobial peptide development and suggests that garlic is a great source of antibacterial peptides and peptide template separations for coping with antibiotic resistance. © 2024 Society of Chemical Industry.

Periodate oxidation-mediated nanocelluloses: Preparation, functionalization, structural design, and applications.

In recent years, the remarkable progress in nanotechnology has ignited considerable interest in investigating nanocelluloses, an environmentally friendly and sustainable nanomaterial derived from cellulosic feedstocks. Current research primarily focuses on the preparation and applications of nanocelluloses. However, to enhance the efficiency of nanofibrillation, reduce energy consumption, and expand nanocellulose applications, chemical pre-treatments of cellulose fibers have attracted substantial interest and extensive exploration. Various chemical pre-treatment methods yield nanocelluloses with diverse functional groups. Among these methods, periodate oxidation has garnered significant attention recently, due to the formation of dialdehyde cellulose derived nanocellulose, which exhibits great promise for further modification with various functional groups. This review seeks to provide a comprehensive and in-depth examination of periodate oxidation-mediated nanocelluloses (PONCs), including their preparation, functionalization, hierarchical structural design, and applications. We believe that PONCs stand as highly promising candidates for the development of novel nano-cellulosic materials.

Alteration of the health effects of bioaerosols by chemical modification in the atmosphere: A review.

Bioaerosols are a subset of important airborne particulates that present a substantial human health hazard due to their allergenicity and infectivity. Chemical reactions in atmospheric processes can significantly influence the health hazard presented by bioaerosols; however, few studies have summarized such alterations to bioaerosols and the mechanisms involved. In this paper, we systematically review the chemical modifications of bioaerosols and the impact on their health effects, mainly focusing on the exacerbation of allergic diseases such as asthma, rhinitis, and bronchitis. Oxidation, nitration, and oligomerization induced by hydroxyl radicals, ozone, and nitrogen dioxide are the major chemical modifications affecting bioaerosols, all of which can aggravate allergenicity mainly through immunoglobulin E pathways. Such processes can even interact with climate change including the greenhouse effect, suggesting the importance of bioaerosols in the future implementation of carbon neutralization strategies. In summary, the chemical modification of bioaerosols and the subsequent impact on health hazards indicate that the combined management of both chemical and biological components is required to mitigate the health hazards of particulate air pollution.

A self-healing thermogelling polymer with tunable transparency based on biomolecule alginate grafting phenylboronic acid.

Thermogelling polymers with transparency, structure stability and biocompatibility are promising for biomedicine application. In this study, a thermogelling polymer P-C5PEG with tunable transparency was developed by the reaction between alternating copolymer C5PEG and chemically modified biomolecule Alg-PBA via boronic ester bonds. The sol-to-gel transition of P-C5PEG aqueous solution sensitively responded to changes in temperature, and the critical value could be adjusted between 15 and 40 °C by varying the content of C5PEG and Alg-PBA. As the weight ratio of Alg-PBA to C5PEG was over 0.3, the transparency of as-synthesized hydrogel kept above 75 % at 37 °C. Meanwhile, immersion P-C5PEG hydrogel in CaCl2 solution significantly increased its mechanical strength by 3 times due to chelation effect. The shear-resistance and self-healing properties were ensured by dynamic boronic ester bonds due to the protective effect of hydrophobic gel network. As a drug delivery, P-C5PEG hydrogel had a swelling rate of 3748.7 ± 103 % in PBS and could continuously release fluorescein sodium within 24 h. Moreover, the in vitro degradability and cytotoxicity of P-C5PEG was confirmed. Finally, the mechanisms behind the thermogelling property and tunable transparency were revealed. Overall, this thermogelling P-C5PEG polymer, with tunable transparency and thermo-responsiveness, exhibits great potential for biomedicine application.

Chemical modification of α-chymotrypsin enabling its release from alginate hydrogel by electrochemically generated local pH change.

This study investigates the controlled release of α-chymotrypsin from an alginate hydrogel matrix. When protein molecules entrapped in the hydrogel matrix have a size smaller than the hydrogel pores, their hold/release from the polymer matrix are controlled by the electrostatic interaction between the guest molecules and host polymer. α-Chymotrypsin, as a model protein, was chemically modified with negatively charged species to change its pI and to convert its attractive interaction with a negatively charged alginate hydrogel matrix to a repulsion interaction allowing its release by pH-triggered signal. Then, bulk pH changes and electrochemically controlled local pH changes resulting from oxygen reduction were used for the controlled release of the enzyme from the alginate hydrogel. Three batches of modified α-chymotrypsin with different linker/enzyme ratios were synthesized, and their release profiles were investigated. The activity of both unmodified and modified α-chymotrypsin was evaluated using a UV-visible spectrophotometer following the standard procedure for the enzymatic assay of α-chymotrypsin (EC 3.4.21.1) and compared across all batches. Direct infusion electrospray ionization mass spectrometry (DI ESI-MS) was used to analyze the protein modifications and their impact on the isoelectric point values.

Simultaneous sensing of carbidopa and levodopa by a novel strategy based on dual-emission ratiometric assay of modified carbon dots.

Rapid control of the content of Parkinson's drugs in biological fluids and pharmaceutical formulations is of great importance because changes in the concentration of these drugs affect their bioavailability and biopharmaceutical properties. Therefore, we presented a simple and convenient method for the ratiometric detection of carbidopa and levodopa for carbon dots (CDs) dual-fluorescent emission. Dual-emission CDs were prepared from chitosan using a microwave method, following which the surface was chemically modified with terephthalaldehyde. CDs had two strong well-separated peaks at 445 and 510 nm. The relative measurement of carbidopa and levodopa was based on the static extinction of CDs at 445 nm and increase at 510 nm, respectively. The linear range for carbidopa measurement was 2.5-300 nM, with a limit of detection (LOD) of 2.1 nM, and a relative standard deviation (RSD) of 1.68%. Further, the linear range for levodopa measurement was equal to 3.0-400 nM, with LOD and RSD% of 2.8 nM and 3.5%, respectively. Also, selectivity of ratiometric sensor in the presence of interferences was investigated, which showed that the recovery of carbidopa and levodopa in serum and urine samples has changed between 96.80% and 116.24% with RSD% 0.11-0.77. CDs also provided good results for the determination of carbidopa and levodopa in real samples, and had high selectivity in the presence of possible interferences.

Rational modification of melatonin for broad-spectrum antifungal agents discovery.

Natural products, known for their environmental safety, are regarded as a significant basis for the modification and advancement of fungicides. Melatonin, as a low-cost natural indole, exhibits diverse biological functions, including antifungal activity. However, its potential as an antifungal agent has not been fully explored. In this study, a series of melatonin derivatives targeting the mitogen-activated protein kinase (Mps1) protein of fungal pathogens were synthesized based on properties of melatonin, among which the trifluoromethyl-substituted derivative Mt-23 exhibited antifungal activity against seven plant pathogenic fungi, and effectively reduced the severity of crop diseases, including rice blast, Fusarium head blight of wheat and gray mold of tomato. In particular, its EC50 (5.4 µM) against the rice blast fungus Magnaporthe oryzae is only one-fourth that of isoprothiolane (22 µM), a commercial fungicide. Comparative analyzes revealed that Mt-23 simultaneously targets the conserved protein kinase Mps1 and lipid protein Cap20. Surface plasmon resonance assays showed that Mt-23 directly binds to Mps1 and Cap20. In this study, we provide a strategy for developing antifungal agents by modifying melatonin, and the resultant melatonin derivative Mt-23 is a commercially valuable, eco-friendly and broad-spectrum antifungal agent to combat crop disease.

Steady-State Delivery and Chemical Modification of Food Nutrients to Improve Cancer Intervention Ability.

Cancer is a crucial global health problem, and prevention is an important strategy to reduce the burden of the disease. Daily diet is the key modifiable risk factor for cancer, and an increasing body of evidence suggests that specific nutrients in foods may have a preventive effect against cancer. This review summarizes the current evidence on the role of nutrients from foods in cancer intervention. It discusses the potential mechanisms of action of various dietary components, including phytochemicals, vitamins, minerals, and fiber. The findings of epidemiological and clinical studies on their association with cancer risk are highlighted. The foods are rich in bioactive compounds such as carotenoids, flavonoids, and ω-3 fatty acids, which have been proven to have anticancer properties. The effects of steady-state delivery and chemical modification of these food's bioactive components on anticancer and intervention are summarized. Future research should focus on identifying the specific bioactive compounds in foods responsible for their intervention effects and exploring the potential synergistic effects of combining different nutrients in foods. Dietary interventions that incorporate multiple nutrients and whole foods may hold promise for reducing the risk of cancer and improving overall health.

Potential structure-function relationships of pectic polysaccharides from quinoa microgreens: Impact of various esterification degrees.

Pectic polysaccharides are one of the most vital functional ingredients in quinoa microgreens, which exhibit numerous health-promoting benefits. Nevertheless, the detailed information about the structure-function relationships of pectic polysaccharides from quinoa microgreens (QMP) remains unknown, thereby largely restricting their applications as functional foods or fortified ingredients. Therefore, to unveil the possible structure-function relationships of QMP, the mild alkali de-esterification was utilized to modify QMP, and then the correlations of esterification degrees of native and modified QMPs to their biological functions were systematically investigated. The results showed that the modified QMPs with different esterification degrees were successfully prepared by the mild alkali treatment, and the primary chemical structure (e.g., compositional monosaccharides and glycosidic linkages) of the native QMP was overall stable after the de-esterified modification. Furthermore, the results revealed that the antioxidant capacity, antiglycation effect, prebiotic potential, and immunostimulatory activity of the native QMP were negatively correlated to its esterification degree. In addition, both native and modified QMPs exerted immunostimulatory effects through activating the TLR4/NF-κB signaling pathway. These results are conducive to unveiling the precise structure-function relationships of QMP, and can also promote its applications as functional foods or fortified ingredients.