Biomolecular study and conjugation of two para-aminobenzoic acid derivatives with serum proteins: drug binding efficacy and protein structural analysis

2020 ◽  
Vol 39 (1) ◽  
pp. 79-90 ◽  
Author(s):  
P. Chanphai ◽  
F. Cloutier ◽  
Y. Oufqir ◽  
M.-F. Leclerc ◽  
A.M. Eiján ◽  
...  
Keyword(s):  
Structural Analysis ◽  
Serum Proteins ◽  
Drug Binding ◽  
Aminobenzoic Acid ◽  
Protein Structural Analysis

scholarly journals Vaccine candidate P6 of nontypable Haemophilus influenzae is not a transmembrane protein based on protein structural analysis

Vaccine ◽  
2011 ◽  
Vol 29 (8) ◽  
pp. 1624-1627 ◽  
Author(s):  
Lea Vacca Michel ◽  
Breanna Kalmeta ◽  
Mark McCreary ◽  
Joy Snyder ◽  
Paul Craig ◽  
...  
Keyword(s):  
Structural Analysis ◽  
Haemophilus Influenzae ◽  
Vaccine Candidate ◽  
Transmembrane Protein ◽  
Protein Structural Analysis

scholarly journals Integrating population variation and protein structural analysis to improve the clinical genetic diagnosis and treatment in children with congenital nephrogenic diabetes insipidus

2020 ◽  
Author(s):  
Panli LIAO ◽  
Tianchao XIANG ◽  
Hongxia LI ◽  
Ye FANG ◽  
Xiaoyan FANG ◽  
...  
Keyword(s):  
Structural Analysis ◽  
Diabetes Insipidus ◽  
Nephrogenic Diabetes Insipidus ◽  
Genetic Disorder ◽  
Genetic Diagnosis ◽  
Isotonic Saline ◽  
Population Variation ◽  
Pathogenic Mutations ◽  
Protein Structural Analysis ◽  
Congenital Nephrogenic Diabetes Insipidus

Abstract Background and Objectives: Congenital nephrogenic diabetes insipidus (NDI) is a rare genetic disorder characterized by renal inability to concentrate urine. Establishing the genetic diagnosis appears particularly important to NDI for early detection and differential diagnosis.Method: We utilized a Chinese multicenter registry to investigate genotype and phenotype in children with NDI from 2014 to 2019. The structural locations of the pathogenic mutations from this study and the literature, as well as population variants retried from gnomAD were analyzed. Results: A total of 10 boys from 9 families carried mutations in AVPR2 (8/10) or AQP2 (2/10). Another 7 relatives of the families were diagnosed by sequencing for partial or subclinical NDI. Patients presented with dehydration, polyuria-polydipsia, and severe hypernatremia with a median age at diagnosis of 1.0 month (IQR 0.16, 18). Protein structural analysis revealed a notable clustering of diagnostic mutations in the transmembrane regions of AVPR2, and enrichment of diagnostic mutations by autosomal dominant inheritance (AD) in the C terminal region of AQP2. The pathogenic mutations are significantly more likely to be buried inside the domain comparing the population variants. Through structural analysis and in silico prediction, the eight mutations identified in this study were considered as presumably disease causative. The most common treatments were thiazide diuretics and non-steroidal anti-inflammatory drugs (NSAIDs). Emergency treatment of hypernatremic dehydration in neonates should not choose the isotonic saline as a rehydration fluid.Conclusion: Genetic analysis presumably confirmed the diagnosis of NDI in every patient of the studied cohort. A plea of early identifying NDI confirmed by phenotype and genotype, and consequently optimize the treatment.

scholarly journals Testing for Ketoprofen Binding to HSA Coated Magnetic Nanoparticles under Normal Conditions and after Oxidative Stress

Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1945 ◽  
Author(s):  
Marta Ziegler-Borowska ◽  
Kinga Mylkie ◽  
Pawel Nowak ◽  
Patryk Rybczynski ◽  
Adam Sikora ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Magnetic Nanoparticles ◽  
Drug Interactions ◽  
Serum Proteins ◽  
Magnetic Core ◽  
Drug Binding ◽  
The Body ◽  
Protein Drug ◽  
Universal Method

Binding and transport of ligands is one of the most important functions of human blood serum proteins. Human serum albumin is found in plasma at the highest concentration. Because of this, it is important to study protein–drug interactions for this albumin. Since there is no single model describing this interaction, it is necessary to measure it for each active substance. Drug binding should also be studied in conditions that simulate pathological conditions of the body, i.e., after oxidative stress. Due to this, it is expected that the methods for testing these interactions need to be easy and fast. In this study, albumin immobilized on magnetic nanoparticles was successfully applied in the study of protein–drug binding. Ketoprofen was selected as a model drug and interactions were tested under normal conditions and artificially induced oxidative stress. The quality of obtained results for immobilized protein was confirmed with those for free albumin and literature data. It was shown that the type of magnetic core coverage does not affect the quality of the obtained results. In summary, a new, fast, effective, and universal method for testing protein–drug interactions was proposed, which can be performed in most laboratories.

scholarly journals Altered Drug Binding to Serum Proteins in Pregnant Women: Therapeutic Relevance

1981 ◽  
Vol 74 (6) ◽  
pp. 422-426 ◽  
Author(s):  
E Peruccam ◽  
M Ruprah ◽  
A Richens
Keyword(s):  
Valproic Acid ◽  
Pregnant Women ◽  
Serum Proteins ◽  
Drug Binding ◽  
Albumin Concentration ◽  
Serum Albumin Concentration ◽  
Partial Explanation ◽  
Unbound Fraction ◽  
Drug Levels

The binding of diazepam, phenytoin and valproic acid to serum proteins in vitro has been compared in pregnant women of different gestational ages and in controls. The unbound fraction of each of the three drugs was elevated during pregnancy (particularly during the last 8 weeks) probably due, at least in part, to a fall in serum albumin concentration. These findings may provide a partial explanation for the increase in the clearance of certain drugs during pregnancy and need to be taken into account when interpreting serum drug levels in clinical practice.

scholarly journals Effect of RBD mutation (Y453F) in spike glycoprotein of SARS-CoV-2 on neutralizing antibody affinity

2020 ◽  
Author(s):  
Takuma Hayashi ◽  
Nobuo Yaegashi ◽  
Ikuo Konishi
Keyword(s):  
Experimental Study ◽  
Monoclonal Antibodies ◽  
Natural Selection ◽  
Structural Analysis ◽  
Growth Process ◽  
Three Dimensional ◽  
Neutralizing Antibody ◽  
Antibody Affinity ◽  
Protein Structural Analysis

AbstractNatural selection “adaptation” in the coronavirus can occur during coronavirus amplification in vivo in farmed minks. Natural selection in such viruses is observed by introduction of mutations in SARS- CoV-2 that are not observed during the growth process in humans. Infection with a mutant (Y453F) of SARS-CoV-2 from farmed minks is known to widely spread among humans. We investigated the virological characteristics of this SARS-CoV-2 mutant (Y453F) using three-dimensional protein structural analysis. Our experimental study suggests that virus variants with the Y453F mutation partially escaped detection by four neutralizing monoclonal antibodies. The spread of SARS-CoV-2 variants mediated by millions of infected farmed minks is uncontrolled; consequently, raising a concern that infection of SARS-CoV-2 mutants that cause serious symptoms in humans may spread globally.

scholarly journals Hemoglobin Cagliari (beta 60 [E4] Val----Glu): a novel unstable thalassemic hemoglobinopathy

Blood ◽  
1991 ◽  
Vol 77 (2) ◽  
pp. 371-375 ◽  
Author(s):  
A Podda ◽  
R Galanello ◽  
L Maccioni ◽  
MA Melis ◽  
C Rosatelli ◽  
...  
Keyword(s):  
Structural Analysis ◽  
Peripheral Blood ◽  
De Novo ◽  
Globin Gene ◽  
De Novo Mutation ◽  
Beta Globin ◽  
Globin Chain ◽  
Thalassemia Intermedia ◽  
Protein Structural Analysis ◽  
Chain Synthesis

Abstract This report describes a patient with thalassemia intermedia-like phenotype born to normal parents in whom globin gene sequencing detected a novel abnormal hemoglobin (Hb) due to a T to A substitution at codon 60 of the beta-globin gene arising as a de novo mutation. Normal sequences were detected at the homologous beta-globin locus. This mutation results in the substitution of a polar (glutamic acid) for a nonpolar (valine) residue near the corner of the heme pocket of the beta-globin chain. The novel variant has been designated Hb Cagliari, from the place of birth of the propositus. Kinetics of globin synthesis performed following splenectomy suggest that this new Hb variant is synthesized at a near normal rate but undergoes rapid breakdown. The extreme lability of the variant explains the clinical and hematologic picture characterized by marked ineffective erythropoiesis, thalassemia-like bone changes, iron overload, high proportion of Hb F in the peripheral blood, reduced beta/alpha-globin chain synthesis ratio in peripheral blood reticulocytes, and absence of the abnormal Hb in peripheral blood at extensive protein structural analysis before splenectomy. This case indicates that a thalassemic hemoglobinopathy should be suspected in the presence of a patient with a thalassemia intermedia-like phenotype born to normal parents, even when protein structural analysis fails to detect an abnormal Hb. DNA sequencing may allow to define the mutation, thus making the proper diagnosis.

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