Abstract:
:The glycoengineering approach is used to improve biophysical properties of protein-based drugs, but its direct impact on binding affinity and kinetic properties for the glycoengineered protein and its binding partner interaction is unclear. Type I interferon (IFN) receptors, composed of IFNAR1 and IFNAR2, have different binding strengths, and sequentially bind to IFN in the dominant direction, leading to activation of signals and induces a variety of biological effects. Here, we evaluated receptor-binding kinetics for each state of binary and ternary complex formation between recombinant human IFN-β-1a and the glycoengineered IFN-β mutein (R27T) using the heterodimeric Fc-fusion technology, and compared biological responses between them. Our results have provided evidence that the additional glycan of R27T, located at the binding interface of IFNAR2, destabilizes the interaction with IFNAR2 via steric hindrance, and simultaneously enhances the interaction with IFNAR1 by restricting the conformational freedom of R27T. Consequentially, altered receptor-binding kinetics of R27T in the ternary complex formation led to a substantial increase in strength and duration of biological responses such as prolonged signal activation and gene expression, contributing to enhanced anti-proliferative activity. In conclusion, our findings reveal N-glycan at residue 25 of R27T is a crucial regulator of receptor-binding kinetics that changes biological activities such as long-lasting activation. Thus, we believe that R27T may be clinically beneficial for patients with multiple sclerosis.
journal_name
Front Pharmacoljournal_title
Frontiers in pharmacologyauthors
Lee S,Son WS,Yang HB,Rajasekaran N,Kim SS,Hong S,Choi JS,Choi JY,Song K,Shin YKdoi
10.3389/fphar.2018.01568subject
Has Abstractpub_date
2019-01-24 00:00:00pages
1568issn
1663-9812journal_volume
9pub_type
杂志文章abstract::The present study reveals a link between protein arginine methyltransferase 5 (PRMT5) and Homebox A9 (HoxA9) in the regulation of cardiomyocyte hypertrophy. In cardiomyocyte hypertrophy induced by β-adrenergic receptor agonist isoprenaline (ISO), PRMT5 expression was decreased while HoxA9 was upregulated. Silencing of...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.600627
更新日期:2020-12-10 00:00:00
abstract::Although the oral route is the most convenient route for drug administration, there are a number of circumstances where this is not possible from either a clinical or pharmaceutical perspective. In these cases, the rectal route may represent a practical alternative and can be used to administer drugs for both local an...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2019.01196
更新日期:2019-10-16 00:00:00
abstract::Objective: Prevalence of osteoporosis in Chinese postmenopausal women has significantly increased over the past decade and oral bisphosphonates are the most potent antiresorptive drugs. The purpose of the present research was to evaluate the cost-effectiveness of oral alendronate for individuals with osteoporosis. We ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.575893
更新日期:2020-11-16 00:00:00
abstract::Scoring functions play an important role in structure-based virtual screening. It has been widely accepted that target-specific scoring functions (TSSFs) may achieve better performance compared with universal scoring functions in actual drug research and development processes. A method that can effectively construct T...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.00924
更新日期:2019-08-22 00:00:00
abstract::Aims: C1q/tumor necrosis factor (TNF)-related protein 5 (CTRP5) belongs to the C1q/TNF-α related protein family and regulates glucose, lipid metabolism, and inflammation production. However, the roles of CTRP5 in ischemia/reperfusion (I/R) associated with cardiac injuries and heart failure (HF) needs to be elaborated....
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.603322
更新日期:2020-12-22 00:00:00
abstract::The cytochrome P450, CYP2C8, metabolizes more than 60 clinically used drugs as well as endogenous substances including retinoic acid and arachidonic acid. However, predictive factors for interindividual variability in the efficacy and toxicity of CYP2C8 drug substrates are essentially lacking. Recently we demonstrated...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2015.00261
更新日期:2015-11-04 00:00:00
abstract::The liver is not only involved in metabolism and detoxification, but also participate in innate immune function and thus exposed to frequent target Thus, they are the frequent target of physical injury. Interestingly, liver has the unique ability to regenerate and completely recoup from most acute, non-iterative situa...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2019.00509
更新日期:2019-05-24 00:00:00
abstract::CLC-K channels belong to the CLC gene family, which comprises both Cl(-) channels and Cl(-)/H(+) antiporters. They form homodimers which additionally co-assemble with the small protein barttin. In the kidney, they are involved in NaCl reabsorption; in the inner ear they are important for endolymph production. Mutation...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2010.00130
更新日期:2010-10-25 00:00:00
abstract::SARS-CoV-2 is a positive sense RNA coronavirus that constitutes a new threat for the global community and economy. While vaccines against SARS-CoV-2 are being developed, the mechanisms through which this virus takes control of an infected cell to replicate remains poorly understood. Upon infection, viruses completely ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2020.578599
更新日期:2020-08-28 00:00:00
abstract::To date, there are no specific therapeutic strategies for treatment of COVID-19. Based on the hypothesis that complement and coagulation cascades are activated by viral infection, and might trigger an acute respiratory distress syndrome (ARDS), we report clinical outcomes of 17 consecutive cases of SARS-CoV-2-related ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.00857
更新日期:2020-06-05 00:00:00
abstract::In spite of recent therapeutic advances, multiple myeloma (MM) remains a malignancy with very low curability. This has been partly attributed to the existence of a drug-resistant subpopulation known as cancer stem cells (CSCs). MM-CSCs are equipped with the necessary tools that render them highly resistant to virtuall...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2017.00610
更新日期:2017-09-08 00:00:00
abstract::Background: HIV pre-exposure prophylaxis (PrEP) with tenofovir/emtricitabine is effective when taken daily. Previously, we developed a urine assay capable of detecting the prodrug tenofovir (TFV) in patients taking tenofovir disoproxil fumarate (TDF)-based PrEP. However, tenofovir alafenamide (TAF) has replaced TDF du...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.00286
更新日期:2020-03-19 00:00:00
abstract::The increase of non-communicable diseases at all ages has fostered the general concern for sustaining population health worldwide. Unhealthy lifestyles and dietary habits impacting physical and psycho-social health are well known risk factors for developing life threatening diseases. Identifying the determinants of qu...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2015.00101
更新日期:2015-05-08 00:00:00
abstract:Background:GuanXinNing tablet (GXNT), a traditional Chinese patent medicine, has been found to have remarkable antithrombotic effects and can effectively inhibit pro-thrombotic factors in previous studies. However, the mechanism of its antithrombotic effects remains little known. Methods:In this study, we first determ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.00652
更新日期:2020-05-13 00:00:00
abstract::Understanding the mechanistic basis for temozolomide (TMZ)-induced glioma resistance is an important obstacle in developing an effective form of chemotherapy for this type of tumor. Glycogenolysis is known to play an essential role in cellular proliferation and potassium homeostasis and involves the glycogen phosphory...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00873
更新日期:2018-08-07 00:00:00
abstract::In Mexico, the Adenophyllum aurantium (L.) Strother plant is consumed as an infusion to treat intestinal diseases such as amoebiasis, which is an endemic health problem in Mexico and other countries. However, the effect of A. aurantium on Entamoeba histolytica, the causative agent of amoebiasis, is unknown. An aerial ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2016.00169
更新日期:2016-06-27 00:00:00
abstract::Pancreatic cancer (PC) is an aggressive and fatal disease with high incidences of metastasis and recurrence. However, there are no effective treatment options for the majority of PC patients, especially for those with locally advanced tumors and metastatic diseases. Therefore, it is urgently needed to develop safe and...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.00457
更新日期:2020-04-08 00:00:00
abstract::The involvement of histamine H3 receptors (H3Rs) in memory is well known, and the potential of H3R antagonists in therapeutic management of neuropsychiatric diseases, e.g., Alzheimer disease (AD) is well established. Therefore, the effects of histamine H3 receptor (H3R) antagonist E159 (2.5-10 mg/kg, i.p.) in adult ma...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2017.00709
更新日期:2017-10-12 00:00:00
abstract::The cardiac action potential is critical to the production of a synchronized heartbeat. This electrical impulse is governed by the intricate activity of cardiac ion channels, among them the cardiac voltage-gated potassium (Kv) channels KCNQ1 and hERG as well as the voltage-gated sodium (Nav) channel encoded by SCN5A. ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2020.00550
更新日期:2020-05-04 00:00:00
abstract::Autophagy is an evolutionary conserved physiological process with a fundamental role during development, differentiation, and survival of eukaryotic cells. On the other hand, autophagy dysregulation is observed in many pathological conditions, including cancer. In particular, tumor growth and progression are accompani...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2020.01141
更新日期:2020-07-24 00:00:00
abstract::Vascular calcification is a major complication of cardiovascular disease and chronic renal failure. Autophagy help to maintain a stable internal and external environment that is important for modulating arteriosclerosis, but its pathogenic mechanism is far from clear. Here, we aimed to identify the bioactive compounds...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.01427
更新日期:2019-12-19 00:00:00
abstract::Introduction and objectives: Metastatic penile squamous cell carcinoma (PSCC) is associated with dismal outcomes with median overall survival (OS) of 6-12 months in the first-line and <6 months in the salvage setting. Given the rarity of this disease, randomized trials are difficult. Prognostic risk models may assist ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2016.00487
更新日期:2016-12-20 00:00:00
abstract::Objective: Children with autism spectrum disorder (ASD) commonly exhibit comorbid symptoms such as aggression, hyperactivity and anxiety. Several studies are being conducted worldwide on cannabidiol use in ASD; however, these studies are still ongoing, and data on the effects of its use is very limited. In this study ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.01521
更新日期:2019-01-09 00:00:00
abstract:Introduction:Acoustic cluster therapy (ACT) comprises co-administration of a formulation containing microbubble/microdroplet clusters (PS101), together with a regular medicinal drug (e.g., a chemotherapeutic) and local ultrasound (US) insonation of the targeted pathological tissue (e.g., the tumor). PS101 is confined t...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.00075
更新日期:2020-02-20 00:00:00
abstract::Lapatinib and capecitabine have been widely used in the therapy of breast cancer. However, long-term use of lapatinib and capecitabine often causes the most common side effect diarrhea, which limit the medicine use. Fructus mume (F. mume) has been proved to be effective to treat chronic diarrhea with few side effects....
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00516
更新日期:2018-05-23 00:00:00
abstract::Acute lung injury (ALI) is a complex syndrome with sepsis occurring in critical patients, who usually lack effective therapy. Nuciferine is a primary bioactive component extracted from the lotus leaf, and it displays extensive pharmacological functions, including anti-cancer, anti-inflammatory, and antioxidant propert...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2017.00939
更新日期:2017-12-21 00:00:00
abstract::Irregular histone modification and aberrant lncRNAs expression are closely related to the occurrence of tumors including acute myeloid leukemia (AML). However, the effects and specific underlying molecular mechanism of histone deacetylase inhibitors on lncRNA expression in AML cells are unclear. Here, we reported the ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.569651
更新日期:2020-10-19 00:00:00
abstract::Asthma is a chronic inflammatory disease characterized by airflow limitation and variable respiratory symptoms. It is characterized by variable symptoms such as cough, wheeze, chest tightness, and shortness of breath which vary in intensity and time. In order to reach a comprehensive approach of disease management, th...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2020.00542
更新日期:2020-05-06 00:00:00
abstract::Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) through the binding of vasoactive intestinal peptide receptors (VIPRs), perform a wide variety of effects in human cancers, including glioblastoma multiforme (GBM). This tumor is characterized by extensive areas of hypox...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2016.00139
更新日期:2016-05-31 00:00:00
abstract::Disorder of the sympathetic nervous system (SNS) is closely related to the pathogenesis of various autoimmune diseases (ADs). Catecholamine triggered beta2-adrenergic receptor (β2-AR) signaling is important in creating a bidirectional response in the progression of ADs due to factors including diverse expression patte...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2018.01313
更新日期:2018-11-27 00:00:00