Publications by authors named "Saeme Asgari"

7 Publications

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UNaProd: A Universal Natural Product Database for of Iranian Traditional Medicine.

Evid Based Complement Alternat Med 2020 13;2020:3690781. Epub 2020 May 13.

Department of Traditional Medicine, School of Persian Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Background: Iranian traditional medicine (ITM) is a holistic medical system that uses a wide range of medicinal substances to treat disease. Reorganization and standardization of the data on ITM concepts is a necessity for optimal use of this rich source. In an initial step towards this goal, we created a database of ITM . . Primarily based on Makhzan al-Advieh, which is the most recent encyclopedia of in ITM with the largest number of monographs, a database of natural medicinal substances was created using both text mining methods and manual editing. UNaProd, a Universal Natural Product database for of ITM, is currently host to 2696 monographs, from herbal to animal to mineral compounds in 16 diverse attributes such as origin and scientific name. Currently, systems biology, and more precisely systems medicine and pharmacology, can be an aid in providing rationalizations for many traditional medicines and elucidating a great deal of knowledge they can offer to guide future research in medicine.

Conclusions: A database of is a stepping stone in creating a systems pharmacology platform of ITM that encompasses the relationships between the drugs, their targets, and diseases. UNaProd is hyperlinked to IrGO and CMAUP databases for and molecular features, respectively, and it is freely available at http://jafarilab.com/unaprod/.
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http://dx.doi.org/10.1155/2020/3690781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243028PMC
May 2020

The effects of overexpression of cytoplasmic chaperones on secretory production of hirudin-PA in E. coli.

Protein Expr Purif 2019 05 29;157:42-49. Epub 2019 Jan 29.

Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran. Electronic address:

The secretory production of heterologous proteins in E. coli has revolutionized biotechnology. Efficient periplasmic production of foreign proteins in E. coli often requires a signal peptide to direct proteins to the periplasm. However, the presence of attached signal peptide does not guarantee periplasmic expression of target proteins. Overproduction of auxiliary proteins, such as chaperones can be a useful approach to enhance protein export. In the current study, three chaperone plasmid sets, including GroEL-GroES (GroELS), Dnak-Dnaj-GrpE (DnaKJE), and trigger factor (TF), were coexpressed in E. coli BL21 (DE3) in a pairwise manner with two pET22-b vectors carrying the recombinant hirudin-PA (Hir) gene and different signal sequences alkaline phosphatase (PhoA) and l-asparaginase II (l-ASP). Overexpression of cytoplasmic combinations of molecular chaperones containing GroELS and DnaKJE with PhoAHir increased the secretory production of PhoAHir by 2.6fold (p < 0.05) and 3.5fold (p < 0.01) compared with their controls, respectively. By contrast, secretory production of PhoAHir significantly reduced in the presence of overexpressed TF (p = 0.02). Further, periplasmic expression of l-ASP was significantly increased only in the presence of DnaKJE (p = 0.04). These findings suggest that using molecular chaperones can be helpful for improving periplasmic expression of Hir. However, tagged signal peptides may affect the physicochemical properties and secondary and tertiary structures of mature Hir, which may alter their interactions with chaperones. Hence, using overexpressed chaperones has various effects on secretory production of PhoAHir and l-ASPHir.
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http://dx.doi.org/10.1016/j.pep.2019.01.011DOI Listing
May 2019

Rational affinity enhancement of fragmented antibody by ligand-based affinity improvement approach.

Biochem Biophys Res Commun 2018 11 26;506(3):653-659. Epub 2018 Oct 26.

Department of Medical Biotechnology and Molecular Science, North Khorasan University of Medical Science, Bojnurd, Iran. Electronic address:

Antibody engineering is now a noteworthy area in biopharmaceuticals as the next generation of marketed antibodies is engineered antibodies such as affinity- or stability-improved antibodies, fragmented or fused antibodies, antibody drug conjugates (ADCs), and PEGylated antibody fragments. In the current study, affinity enhancement of Nb against PlGF was performed by an in silico affinity maturation and molecular dynamics (MD) simulation. First, 300 single-point mutants were designed by identifying the residues involved in interaction with PlGF and different energy distributions. An energy based screening was performed to select best single-point mutants. Additionally, one variant containing two mutations was designed based on the selected single-point mutants. Finally, mutants-PlGF complexes were analyzed in details by all atom MD simulation. Trajectory analysis revealed that in both single (L112H, S31D, A97K, and R45E) and double (S31D & R45E) mutants, the free binding energies and the stability of complexes were significantly improved. The highest increment in affinity was observed for S31D mutant due to substantial increase in polar and electrostatic interactions. The secondary structure of Nb was intact in all variants and a shrinkage of PlGF over Nb was observed in all mutant-PlGF complexes during simulation. In addition, contact area and hydrogen-bond analysis as well as distance measurement in mutants-PlGF complexes also confirmed the affinity enhancement of variants relative to the native form. Our study showed that ligand-based affinity improvement could be considered as a promising approach for designing high affinity fragmented antibodies.
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http://dx.doi.org/10.1016/j.bbrc.2018.10.127DOI Listing
November 2018

Therapeutic protein deimmunization by T-cell epitope removal: antigen-specific immune responses in vitro and in vivo.

APMIS 2017 Jun 18;125(6):544-552. Epub 2017 Apr 18.

Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.

Hirudin III is an effective anti-coagulant; however, in 40% of treated patients, a high-titer of anti-Hirudin III IgG antibodies is observed. Development of antibody responses requires the activation of helper T lymphocyte (HTL), which is dependent on peptide epitopes binding to HLA class II molecules. Based on computational prediction softwares, four new mutants of Hirudin III, T4K, S9G, V21G, and V21K, had been designed with the aim of reducing the binding affinity of these HTL epitopes. The constructed mutants have been purified and assayed for bioactivity. Finally in vitro and in vivo cell-mediated responses were assessed and humoral immune assays were performed. All modified forms of Hirudin III were active, and showed significantly reduced human T-cell responses. All mutants indicated lower human IFN-γ level compared to native Hirudin, and V21K indicated lowest IFN-γ level. Mice immunized with T4K and V21K showed a significant reduction in total antibody responses and mouse IFN-γ levels. Mice immunized with V21K after 3rd immunization had lower T-cell proliferation compared to native Hirudin and other mutants. Based on these results, V21K is proposed as the best alternate Hirudin III candidate with lowest antigenicity. These findings validate our rational design strategy aimed at providing new active analogs of therapeutic proteins with reduced immunogenicity.
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http://dx.doi.org/10.1111/apm.12682DOI Listing
June 2017

Corrigendum to "The first report on transcriptome analysis of the venom gland of Iranian scorpion, Hemiscorpius lepturus" [Toxicon 125 (2017) 123-130].

Toxicon 2017 03 10;128:60. Epub 2017 Feb 10.

Venom & Biotherapeutics Molecules Laboratory, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran. Electronic address:

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http://dx.doi.org/10.1016/j.toxicon.2017.01.012DOI Listing
March 2017

Rational design of stable and functional hirudin III mutants with lower antigenicity.

Biologicals 2015 Nov 25;43(6):479-91. Epub 2015 Aug 25.

Biosensor Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran; Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Hirudin is an inhibitor of thrombin and used as an effective anticoagulant, but has a potential to develop unacceptable immune responses. In this study, two computational tools were used to predict T-cell epitopes within Hirudin variant III (HVIII) sequence, and design mutations that would lessen its antigenicity. Homology models of native and mutant HVIII proteins (T4K, S9G, V21G, and V21K) were generated, and further used to assess their interactions with thrombin. The docking experiment showed that all mutants had a suitable pattern of interactions, with similar or lower interaction energies compared with the native protein. These complexes were subsequently subjected to molecular dynamics simulation. All mutants complexes had overall stable structures over simulation time, with RMSD, gyration radius, hydrogen bonds numbers, and accessible surface areas patterns that were comparable with the native HVIII over time. Interestingly, in all mutants, a shorter length was observed for the two salt bridges Arg73-Asp55 and Arg77-Glu57, which are suggested to be important in Hirudin-thrombin complex formation. Best selected mutants expressed in Escherichia coli BL21(DE3), subsequently SDS-PAGE and Western blot analysis confirmed the successful same expression of Hirudin and mutants. In conclusion, we believe that this computational approach could identify potentially safer proteins with preserved or even improved functionality.
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http://dx.doi.org/10.1016/j.biologicals.2015.07.008DOI Listing
November 2015

Targeting acetate kinase: inhibitors as potential bacteriostatics.

J Microbiol Biotechnol 2013 Nov;23(11):1544-53

Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

Despite the importance of acetate kinase in the metabolism of bacteria, limited structural studies have been carried out on this enzyme. In this study, a three-dimensional structure of the Escherichia coli acetate kinase was constructed by use of molecular modeling methods. In the next stage, by considering the structure of the catalytic intermediate, trifluoroethanol (TFE) and trifluoroethyl butyrate were proposed as potential inhibitors of the enzyme. The putative binding mode of these compounds was studied with the use of a docking program, which revealed that they can fit well into the enzyme. To study the role of these potential enzyme inhibitors in the metabolic pathway of E. coli, their effects on the growth of this bacterium were studied. The results showed that growth was considerably reduced in the presence of these inhibitors. Changes in the profile of the metabolic products were studied by proton nuclear magnetic resonance spectroscopy. Remarkable changes were observed in the quantity of acetate, but other products were less altered. In this study, inhibition of growth by the two inhibitors as reflected by a change in the metabolism of E. coli suggests the potential use of these compounds (particularly TFE) as bacteriostatic agents.
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http://dx.doi.org/10.4014/jmb.1305.05026DOI Listing
November 2013