Displaying publications 1 - 20 of 352 in total

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  1. E M Eid E, S Alanazi A, Koosha S, A Alrasheedy A, Azam F, M Taban I, et al.
    Molecules, 2019 Jul 13;24(14).
    PMID: 31337024 DOI: 10.3390/molecules24142554
    Cell-penetrating peptides (CPPs) are highly promising tools to deliver therapeutic molecules into tumours. αVβ3 integrins are cell-matrix adhesion receptors, and are considered as an attractive target for anticancer therapies owing to their roles in the process of metastasis and angiogenesis. Therefore, this study aims to assess the effect of co-administration of zerumbone (ZER) and ZERencapsulated in hydroxypropyl-β-cyclodextrin with TP5-iRGD peptide towards cell cytotoxicity, apoptosis induction, and proliferation of normal and cancerous breast cells utilizing in vitro assays, as well as to study the molecular docking of ZER in complex with TP5-iRGD peptide. Cell viability assay findings indicated that ZER and ZERencapsulated in hydroxypropyl-β-cyclodextrin (ZER-HPβCD) inhibited the growth of estrogen receptor positivebreast cancer cells (ER+ MCF-7) at 72 h treatment with an inhibitory concentration (IC)50 of 7.51 ± 0.2 and 5.08 ± 0.2 µg/mL, respectively, and inhibited the growth of triple negative breast cancer cells (MDA-MB-231) with an IC50 of 14.96 ± 1.52 µg/mL and 12.18 ± 0.7 µg/mL, respectively. On the other hand, TP5-iRGD peptide showed no significant cytotoxicity on both cancer and normal cells. Interestingly, co-administration of TP5-iRGD peptide in MCF-7 cells reduced the IC50 of ZER from 7.51 ± 0.2 µg/mL to 3.13 ± 0.7 µg/mL and reduced the IC50 of ZER-HPβCD from 5.08 ± 0.2 µg/mL to 0.49 ± 0.004 µg/mL, indicating that the co-administration enhances the potency and increases the efficacy of ZER and ZER-HPβCD compounds. Acridine orange (AO)/propidium iodide (PI) staining under fluorescence microscopy showed evidence of early apoptosis after 72 h from the co-administration of ZER or ZER-HPβCD with TP5-iRGD peptide in MCF-7 breast cancer cells. The findings of the computational modelling experiment provide novel insights into the ZER interaction with integrin αvβ3 in the presence of TP5-iRGD, and this could explain why ZER has better antitumor activities when co-administered with TP5-iRGD peptide.
    Matched MeSH terms: Models, Molecular
  2. Jusoh N, Zainal H, Abdul Hamid AA, Bunnori NM, Abd Halim KB, Abd Hamid S
    J Mol Model, 2018 Mar 15;24(4):93.
    PMID: 29546582 DOI: 10.1007/s00894-018-3619-6
    Recent outbreaks of highly pathogenic influenza strains have highlighted the need to develop new anti-influenza drugs. Here, we report an in silico study of carvone derivatives to analyze their binding modes with neuraminidase (NA) active sites. Two proposed carvone analogues, CV(A) and CV(B), with 36 designed ligands were predicted to inhibit NA (PDB ID: 3TI6) using molecular docking. The design is based on structural resemblance with the commercial inhibitor, oseltamivir (OTV), ligand polarity, and amino acid residues in the NA active sites. Docking simulations revealed that ligand A18 has the lowest energy binding (∆Gbind) value of -8.30 kcal mol-1, comparable to OTV with ∆Gbind of -8.72 kcal mol-1. A18 formed seven hydrogen bonds (H-bonds) at residues Arg292, Arg371, Asp151, Trp178, Glu227, and Tyr406, while eight H-bonds were formed by OTV with amino acids Arg118, Arg292, Arg371, Glu119, Asp151, and Arg152. Molecular dynamics (MD) simulation was conducted to compare the stability between ligand A18 and OTV with NA. Our simulation study showed that the A18-NA complex is as stable as the OTV-NA complex during the MD simulation of 50 ns through the analysis of RMSD, RMSF, total energy, hydrogen bonding, and MM/PBSA free energy calculations.
    Matched MeSH terms: Models, Molecular*
  3. Frimayanti N, Zain SM, Lee VS, Wahab HA, Yusof R, Abd Rahman N
    In Silico Biol. (Gedrukt), 2011;11(1-2):29-37.
    PMID: 22475750 DOI: 10.3233/ISB-2012-0442
    Publication year=2011-2012
    Matched MeSH terms: Models, Molecular
  4. Gwaram NS, Ali HM, Abdulla MA, Buckle MJ, Sukumaran SD, Chung LY, et al.
    Molecules, 2012 Feb 28;17(3):2408-27.
    PMID: 22374313 DOI: 10.3390/molecules17032408
    Alzheimer's disease (AD) is the most common form of dementia among older people and the pathogenesis of this disease is associated with oxidative stress. Acetylcholinesterase inhibitors with antioxidant activities are considered potential treatments for AD. Some novel ketone derivatives of gallic hydrazide-derived Schiff bases were synthesized and examined for their antioxidant activities and in vitro and in silico acetyl cholinesterase inhibition. The compounds were characterized using spectroscopy and X-ray crystallography. The ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays revealed that all the compounds have strong antioxidant activities. N-(1-(5-bromo-2-hydroxyphenyl)-ethylidene)-3,4,5-trihydroxybenzohydrazide (2) was the most potent inhibitor of human acetyl cholinesterase, giving an inhibition rate of 77% at 100 μM. Molecular docking simulation of the ligand-enzyme complex suggested that the ligand may be positioned in the enzyme's active-site gorge, interacting with residues in the peripheral anionic subsite (PAS) and acyl binding pocket (ABP). The current work warrants further preclinical studies to assess the potential for these novel compounds for the treatment of AD.
    Matched MeSH terms: Models, Molecular
  5. Shameli K, Ahmad MB, Yunus WM, Rustaiyan A, Ibrahim NA, Zargar M, et al.
    Int J Nanomedicine, 2010 Oct 22;5:875-87.
    PMID: 21116328 DOI: 10.2147/IJN.S13632
    In this study, silver nanoparticles (Ag-NPs) were synthesized using a green physical synthetic route into the lamellar space of montmorillonite (MMT)/chitosan (Cts) utilizing the ultraviolet (UV) irradiation reduction method in the absence of any reducing agent or heat treatment. Cts, MMT, and AgNO(3) were used as the natural polymeric stabilizer, solid support, and silver precursor, respectively. The properties of Ag/MMT/Cts bionanocomposites (BNCs) were studied as the function of UV irradiation times. UV irradiation disintegrated the Ag-NPs into smaller sizes until a relatively stable size and size distribution were achieved. Meanwhile, the crystalline structure and d-spacing of the MMT interlayer, average size and size distribution, surface morphology, elemental signal peaks, functional groups, and surface plasmon resonance of Ag/MMT/Cts BNCs were determined by powder X-ray diffraction, transmission electron microscopy, scanning electron microscopy, energy dispersive X-ray fluorescence, Fourier transform infrared, and UV-visible spectroscopy. The antibacterial activity of Ag-NPs in MMT/Cts was investigated against Gram-positive bacteria, ie, Staphylococcus aureus and methicillin-resistant S. aureus and Gram-negative bacteria (ie, Escherichia coli) by the disk diffusion method on Muller-Hinton Agar at different sizes of Ag-NPs. All of the synthesized Ag/MMT/Cts BNCs were found to have high antibacterial activity. These results show that Ag/MMT/Cts BNCs can be useful in different biologic research and biomedical applications, such as surgical devices and drug delivery vehicles.
    Matched MeSH terms: Models, Molecular
  6. Hussein MA, Guan TS, Haque RA, Khadeer Ahamed MB, Abdul Majid AM
    Spectrochim Acta A Mol Biomol Spectrosc, 2015 Feb 05;136 Pt C:1335-48.
    PMID: 25456676 DOI: 10.1016/j.saa.2014.10.021
    Four dioxomolybdenum(VI) complexes were synthesized by reacting [MoO2(acac)2] with N-ethyl-2-(5-bromo-2-hydroxybenzylidene) hydrazinecarbothioamide (1), N-ethyl-2-(5-allyl-3-methoxy-2-hydroxybenzylidene) hydrazinecarbothioamide (2), N-methyl-2-(3-tert-butyl-2-hydroxybenzylidene) hydrazinecarbothioamide (3), and N-ethyl-2-(3-methyl-2-hydroxybenzylidene) hydrazinecarbothioamide (4). The molecular structures of 1, 2, and all the synthesized complexes were determined using single crystal X-ray crystallography. The binding properties of the ligand and complexes with calf thymus DNA (CT-DNA) were investigated via UV, fluorescence titrations, and viscosity measurement. Gel electrophoresis revealed that all the complexes cleave pBR 322 plasmid DNA. The cytotoxicity of the complexes were studied against the HCT 116 human colorectal cell line. All the complexes exhibited more pronounced activity than the standard reference drug 5-fluorouracil (IC50 7.3μM). These studies show that dioxomolybdenum(VI) complexes could be potentially useful in chemotherapy.
    Matched MeSH terms: Models, Molecular
  7. Iqbal MA, Haque RA, Ahamed SA, Jafari SF, Khadeer Ahamed MB, Abdul Majid AM
    Med Chem, 2015;11(5):473-81.
    PMID: 25553509
    Azolium (imidazolium and benzimidazolium) salts are known as stable precursors for the synthesis of Metal-N-Heterocyclic Carbene (M-NHC) complexes. Recently, some reports have been compiled indicating that benzimidazolium salts have anticarcinogenic properties. The current research is the further investigation of this phenomenon. Three ortho-xylene linked bis-benzimidazolium salts (1-3) with octyl, nonyl and decyl terminal chain lengths have been synthesized. Each of the compounds was characterized using FT-IR and NMR spectroscopic techniques. The molecular geometries of two of the salts (1-2) have been established using X-ray crystallographic technique. The compounds were tested for their cytotoxic properties against three cancerous cell lines namely, human colon cancer (HCT 116), human colorectal adenocarcinoma (HT- 29) and human breast adenocarcinoma (MCF-7). Mouse embryonic fibroblast (3T3-L1) was used as the model cell line of normal cells. The compounds showed selective anti-proliferative activities against the colorectal carcinoma cells. For HCT 116 and HT-29 cells, the IC50 values ranged 0.9-2.6 µM and 4.0-10.0 µM, respectively. The salts 1 and 3 displayed moderate cytotoxicity against the breast cancer (MCF-7) cells with IC50 58.2 and 13.3 µM, respectively. However, the salt 2 produced strong cytotoxicity against MCF-7 cells with IC50 4.4 µM. Interestingly, the compounds demonstrated poor cytotoxic effects towards the normal cells (3T3-L1) as the IC50 was found to be as high as 48.0 µM. Salts 2 and 3 demonstrated more pronounced anti-proliferative effect than the standard drugs used (5-Flourouracil and Tamoxifen).
    Matched MeSH terms: Models, Molecular*
  8. Ali AQ, Teoh SG, Salhin A, Eltayeb NE, Khadeer Ahamed MB, Abdul Majid AM
    PMID: 24607427 DOI: 10.1016/j.saa.2014.01.086
    New derivatives of thiosemicarbazone Schiff base with isatin moiety were synthesized L1-L6. The structures of these compounds were characterized based on the spectroscopic techniques. Compound L6 was further characterized by XRD single crystal. The interaction of these compounds with calf thymus (CT-DNA) exhibited high intrinsic binding constant (k(b)=5.03-33.00×10(5) M(-1)) for L1-L3 and L5 and (6.14-9.47×10(4) M(-1)) for L4 and L6 which reflect intercalative activity of these compounds toward CT-DNA. This result was also confirmed by the viscosity data. The electrophoresis studies reveal the higher cleavage activity of L1-L3 than L4-L6. The in vitro anti-proliferative activity of these compounds against human colon cancer cell line (HCT 116) revealed that the synthesized compounds (L3, L6 and L2) exhibited good anticancer potency.
    Matched MeSH terms: Models, Molecular
  9. Helal MH, Al-Mudaris ZA, Al-Douh MH, Osman H, Wahab HA, Alnajjar BO, et al.
    Int J Oncol, 2012 Aug;41(2):504-10.
    PMID: 22614449 DOI: 10.3892/ijo.2012.1491
    Molecules that target the deoxyribonucleic acid (DNA) minor groove are relatively sequence specific and they can be excellent carrier structures for cytotoxic chemotherapeutic compounds which can help to minimize side effects. Two novel isomeric derivatives of diaminobenzene Schiff base [N,N'-bis (2-hydroxy-3-methoxybenzylidene)-1,2-diaminobenzene (2MJ) and N,N'-bis(2-hydroxy-3-methoxybenzylidene)-1,3-diaminobenzene (2MH)] were analyzed for their DNA minor groove binding (MGB) ability using viscometry, UV and fluorescence spectroscopy, computational modeling and clonogenic assay. The result shows that 2MJ and 2MH are strong DNA MGBs with the latter being more potent. 2MH can form interstrand hydrogen bond linkages at its oxygens with N3 of adenines. Changing the 2-hydroxy-3-methoxybenzylidene binding position to the 1,3 location on the diaminobenzene structure (2MJ) completely removed any viable hydrogen bond formation with the DNA and caused significant decrease in binding strength and minor groove binding potency. Neither compound showed any significant cytotoxicity towards human breast, colon or liver cancer cell lines.
    Matched MeSH terms: Models, Molecular
  10. Yusof NA, Kamaruddin S, Abu Bakar FD, Mahadi NM, Abdul Murad AM
    Cell Stress Chaperones, 2019 Mar;24(2):351-368.
    PMID: 30649671 DOI: 10.1007/s12192-019-00969-1
    Studies on TCP1-1 ring complex (TRiC) chaperonin have shown its indispensable role in folding cytosolic proteins in eukaryotes. In a psychrophilic organism, extreme cold temperature creates a low-energy environment that potentially causes protein denaturation with loss of activity. We hypothesized that TRiC may undergo evolution in terms of its structural molecular adaptation in order to facilitate protein folding in low-energy environment. To test this hypothesis, we isolated G. antarctica TRiC (GaTRiC) and found that the expression of GaTRiC mRNA in G. antarctica was consistently expressed at all temperatures indicating their importance in cell regulation. Moreover, we showed GaTRiC has the ability of a chaperonin whereby denatured luciferase can be folded to the functional stage in its presence. Structurally, three categories of residue substitutions were found in α, β, and δ subunits: (i) bulky/polar side chains to alanine or valine, (ii) charged residues to alanine, and (iii) isoleucine to valine that would be expected to increase intramolecular flexibility within the GaTRiC. The residue substitutions observed in the built structures possibly affect the hydrophobic, hydrogen bonds, and ionic and aromatic interactions which lead to an increase in structural flexibility. Our structural and functional analysis explains some possible structural features which may contribute to cold adaptation of the psychrophilic TRiC folding chamber.
    Matched MeSH terms: Models, Molecular
  11. Tan BH, Chor Leow T, Foo HL, Abdul Rahim R
    Biomed Res Int, 2014;2014:469298.
    PMID: 24592392 DOI: 10.1155/2014/469298
    A superoxide dismutase (SOD) gene of Lactococcus lactis M4 was cloned and expressed in a prokaryotic system. Sequence analysis revealed an open reading frame of 621 bp which codes for 206 amino acid residues. Expression of sodA under T7 promoter exhibited a specific activity of 4967 U/mg when induced with 1 mM of isopropyl-β-D-thiogalactopyranoside. The recombinant SOD was purified to homogeneity by immobilised metal affinity chromatography and Superose 12 gel filtration chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blot analyses of the recombinant SOD detected a molecular mass of approximately 27 kDa. However, the SOD was in dimer form as revealed by gel filtration chromatography. The purified recombinant enzyme had a pI of 4.5 and exhibited maximal activity at 25°C and pH 7.2. It was stable up to 45°C. The insensitivity of this lactococcal SOD to cyanide and hydrogen peroxide established that it was a MnSOD. Although it has 98% homology to SOD of L. lactis IL1403, this is the first elucidated structure of lactococcal SOD revealing active sites containing the catalytic manganese coordinated by four ligands (H-27, H-82, D-168, and H-172).
    Matched MeSH terms: Models, Molecular*
  12. Begum SZ, Nizam NSM, Muhamad A, Saiman MI, Crouse KA, Abdul Rahman MB
    PLoS One, 2020;15(11):e0238147.
    PMID: 33147237 DOI: 10.1371/journal.pone.0238147
    Laccases, oxidative copper-enzymes found in fungi and bacteria were used as the basis in the design of nona- and tetrapeptides. Laccases are known to be excellent catalysts for the degradation of phenolic xenobiotic waste. However, since solvent extraction of laccases is environmentally-unfriendly and yields obtained are low, they are less preferred compared to synthetic catalysts. The histidine rich peptides were designed based on the active site of laccase extracted from Trametes versicolor through RCSB Protein Data Bank, LOMETS and PyMol software. The peptides were synthesized using Fmoc-solid phase peptide synthesis (SPPS) with 30-40% yield. These peptides were purified and characterized using LC-MS (purities >75%), FTIR and NMR spectroscopy. Synthesized copper(II)-peptides were crystallized and then analyzed spectroscopically. Their structures were elucidated using 1D and 2D NMR. Standards (o,m,p-cresol, 2,4-dichlorophenol) catalysed using laccase from Trametes versicolor (0.66 U/mg) were screened under different temperatures and stirring rate conditions. After optimizing the degradation of the standards with the best reaction conditions reported herein, medications with phenolic and aromatic structures such as ibuprofen, paracetamol (acetaminophen), salbutamol, erythromycin and insulin were screened using laccase (positive control), apo-peptides and copper-peptides. Their activities evaluated using GC-MS, were compared with those of peptide and copper-peptide catalysts. The tetrapeptide was found to have the higher degradation activity towards salbutamol (96.8%) compared with laccase at 42.8%. Ibuprofen (35.1%), salbutamol (52.9%) and erythromycin (49.7%) were reported to have the highest degradation activities using Cu-tetrapeptide as catalyst when compared with the other medications. Consequently, o-cresol (84%) was oxidized by Tp-Cu while the apo-peptides failed to oxidize the cresols. Copper(II)-peptides were observed to have higher catalytic activity compared to their parent peptides and the enzyme laccase for xenobiotic degradation.
    Matched MeSH terms: Models, Molecular
  13. Arunagiri C, Subashini A, Saranya M, Thomas Muthiah P, Thanigaimani K, Abdul Razak I
    PMID: 25084236 DOI: 10.1016/j.saa.2014.07.016
    The molecular structure of a new Schiff base, 2-[4-hydroxy benzylidene]-amino naphthalene (HBAN) has been examined by HF and B3LYP/6-311++G(d,p) calculations. The X-ray structure was determined in order to establish the conformation of the molecule. The compound, C17H13NO, crystallizes in the orthorhombic, P212121 space group with the cell dimension, a=6.2867(2), b=10.2108(3), c=19.2950(6) Å, α=β=γ=90° and z=4. The asymmetric unit contains a molecule of a Schiff base. A strong intermolecular O-H⋯N and a weak C-H⋯O hydrogen bonds stabilized the crystal structure. The vibrational spectra of HBAN have been calculated using density functional theoretical computation and compared with the experimental. The study is extended to the HOMO-LUMO analysis to calculate the energy gap (Δ), Ionization potential (I), Electron Affinity (A), Global Hardness (η), Chemical Potential (μ) and Global Electrophilicity (w). The calculated HOMO and LUMO energy reveals that the charge transfer occurs within the molecule.
    Matched MeSH terms: Models, Molecular*
  14. Abedi Karjiban R, Abdul Rahman MB, Basri M, Salleh AB, Jacobs D, Abdul Wahab H
    Protein J, 2009 Jan;28(1):14-23.
    PMID: 19130194 DOI: 10.1007/s10930-008-9159-7
    Molecular Dynamics (MD) simulations have been used to understand how protein structure, dynamics, and flexibility are affected by adaptation to high temperature for several years. We report here the results of the high temperature MD simulations of Bacillus stearothermophilus L1 (L1 lipase). We found that the N-terminal moiety of the enzyme showed a high flexibility and dynamics during high temperature simulations which preceded and followed by clear structural changes in two specific regions; the small domain and the main catalytic domain or core domain of the enzyme. These two domains interact with each other through a Zn(2+)-binding coordination with Asp-61 and Asp-238 from the core domain and His-81 and His-87 from the small domain. Interestingly, the His-81 and His-87 were among the highly fluctuated and mobile residues at high temperatures. The results appear to suggest that tight interactions of Zn(2+)-binding coordination with specified residues became weak at high temperature which suggests the contribution of this region to the thermostability of the enzyme.
    Matched MeSH terms: Models, Molecular*
  15. Zainol S, Basri M, Basri HB, Shamsuddin AF, Abdul-Gani SS, Karjiban RA, et al.
    Int J Mol Sci, 2012;13(10):13049-64.
    PMID: 23202937 DOI: 10.3390/ijms131013049
    Response surface methodology (RSM) was utilized to investigate the influence of the main emulsion composition; mixture of palm and medium-chain triglyceride (MCT) oil (6%-12% w/w), lecithin (1%-3% w/w), and Cremophor EL (0.5%-1.5% w/w) as well as the preparation method; addition rate (2-20 mL/min), on the physicochemical properties of palm-based nanoemulsions. The response variables were the three main emulsion properties; particle size, zeta potential and polydispersity index. Optimization of the four independent variables was carried out to obtain an optimum level palm-based nanoemulsion with desirable characteristics. The response surface analysis showed that the variation in the three responses could be depicted as a quadratic function of the main composition of the emulsion and the preparation method. The experimental data could be fitted sufficiently well into a second-order polynomial model. The optimized formulation was stable for six months at 4 °C.
    Matched MeSH terms: Models, Molecular
  16. Ling I, Taha M, Al-Sharji NA, Abou-Zied OK
    PMID: 29316482 DOI: 10.1016/j.saa.2018.01.005
    The ability of human serum albumin (HSA) to bind medium-sized hydrophobic molecules is important for the distribution, metabolism, and efficacy of many drugs. Herein, the interaction between pyrene, a hydrophobic fluorescent probe, and HSA was thoroughly investigated using steady-state and time-resolved fluorescence techniques, ligand docking, and molecular dynamics (MD) simulations. A slight quenching of the fluorescence signal from Trp214 (the sole tryptophan residue in the protein) in the presence of pyrene was used to determine the ligand binding site in the protein, using Förster's resonance energy transfer (FRET) theory. The estimated FRET apparent distance between pyrene and Trp214 was 27Å, which was closely reproduced by the docking analysis (29Å) and MD simulation (32Å). The highest affinity site for pyrene was found to be in subdomain IB from the docking results. The calculated equilibrium structure of the complex using MD simulation shows that the ligand is largely stabilized by hydrophobic interaction with Phe165, Phe127, and the nonpolar moieties of Tyr138 and Tyr161. The fluorescence vibronic peak ratio I1/I3 of bound pyrene inside HSA indicates the presence of polar effect in the local environment of pyrene which is less than that of free pyrene in buffer. This was clarified by the MD simulation results in which an average of 5.7 water molecules were found within 0.5nm of pyrene in the binding site. Comparing the fluorescence signals and lifetimes of pyrene inside HSA to that free in buffer, the high tendency of pyrene to form dimer was almost completely suppressed inside HSA, indicating a high selectivity of the binding pocket toward pyrene monomer. The current results emphasize the ability of HSA, as a major carrier of several drugs and ligands in blood, to bind hydrophobic molecules in cavities other than subdomain IIA which is known to bind most hydrophobic drugs. This ability stems from the nature of the amino acids forming the binding sites of the protein that can easily adapt their shape to accommodate a variety of molecular structures.
    Matched MeSH terms: Models, Molecular*
  17. Wan Ibrahim WA, Abd Ali LI, Sulaiman A, Sanagi MM, Aboul-Enein HY
    Crit Rev Anal Chem, 2014;44(3):233-54.
    PMID: 25391563 DOI: 10.1080/10408347.2013.855607
    The progress of novel sorbents and their function in preconcentration techniques for determination of trace elements is a topic of great importance. This review discusses numerous analytical approaches including the preparation and practice of unique modification of solid-phase materials. The performance and main features of ion-imprinting polymers, carbon nanotubes, biosorbents, and nanoparticles are described, covering the period 2007-2012. The perspective and future developments in the use of these materials are illustrated.
    Matched MeSH terms: Models, Molecular
  18. Al Azzam KM, Saad B, Adnan R, Aboul-Enein HY
    Anal Chim Acta, 2010 Aug 3;674(2):249-55.
    PMID: 20678638 DOI: 10.1016/j.aca.2010.06.046
    A capillary electrophoretic method for the separation of the enantiomers of both ofloxacin and ornidazole is described. Several parameters affecting the separation were studied, including the type and concentration of chiral selector, buffer pH, voltage and temperature. Good chiral separation of the racemic mixtures was achieved in less than 16 min with resolution factors Rs=5.45 and 6.28 for ofloxacin and ornidazole enantiomers, respectively. Separation was conducted using a bare fused-silica capillary and a background electrolyte (BGE) of 50 mM H(3)PO(4)-1 M tris solution; pH 1.85; containing 30 mg mL(-1) of sulfated-beta-cyclodextrin (S-beta-CD). The separation was carried out in reversed polarity mode at 25 degrees C, 18 kV, detection wavelength at 230 nm and using hydrodynamic injection for 15 s. Acceptable validation criteria for selectivity, linearity, precision, and accuracy were studied. The limits of detection (LOD) and limits of quantitation (LOQ) of the enantiomers (ofloxacin enantiomer 1 (OF-E1), ofloxacin enantiomer 2 (OF-E2), ornidazole enantiomer 1 (OR-E1) and ornidazole enantiomer 2 (OR-E2)) were (0.52, 0.46, 0.54, 0.89) and (1.59, 1.40, 3.07, 2.70) microg mL(-1), respectively. The proposed method was successfully applied to the assay of enantiomers of both ofloxacin and ornidazole in pharmaceutical formulations. The computational calculations for the enantiomeric inclusion complexes rationalized the reasons for the different migration times between the ofloxacin and ornidazole enantiomers.
    Matched MeSH terms: Models, Molecular
  19. Chin IS, Abdul Murad AM, Mahadi NM, Nathan S, Abu Bakar FD
    Protein Eng. Des. Sel., 2013 May;26(5):369-75.
    PMID: 23468570 DOI: 10.1093/protein/gzt007
    Cutinase has been ascertained as a biocatalyst for biotechnological and industrial bioprocesses. The Glomerella cingulata cutinase was genetically modified to enhance its enzymatic performance to fulfill industrial requirements. Two sites were selected for mutagenesis with the aim of altering the surface electrostatics as well as removing a potentially deamidation-prone asparagine residue. The N177D cutinase variant was affirmed to be more resilient to temperature increase with a 2.7-fold increase in half-life at 50°C as compared with wild-type enzyme, while, the activity at 25°C is not compromised. Furthermore, the increase in thermal tolerance of this variant is accompanied by an increase in optimal temperature. Another variant, the L172K, however, exhibited higher enzymatic performance towards phenyl ester substrates of longer carbon chain length, yet its thermal stability is inversely affected. In order to restore the thermal stability of L172K, we constructed a L172K/N177D double variant and showed that these two mutations yield an improved variant with enhanced activity towards phenyl ester substrates and enhanced thermal stability. Taken together, our study may provide valuable information for enhancing catalytic performance and thermal stability in future engineering endeavors.
    Matched MeSH terms: Models, Molecular
  20. Jaafar NR, Littler D, Beddoe T, Rossjohn J, Illias RM, Mahadi NM, et al.
    Acta Crystallogr F Struct Biol Commun, 2016 11 01;72(Pt 11):831-839.
    PMID: 27827354
    Fuculose-1-phosphate aldolase (FucA) catalyses the reversible cleavage of L-fuculose 1-phosphate to dihydroxyacetone phosphate (DHAP) and L-lactaldehyde. This enzyme from mesophiles and thermophiles has been extensively studied; however, there is no report on this enzyme from a psychrophile. In this study, the gene encoding FucA from Glaciozyma antarctica PI12 (GaFucA) was cloned and the enzyme was overexpressed in Escherichia coli, purified and crystallized. The tetrameric structure of GaFucA was determined to 1.34 Å resolution. The overall architecture of GaFucA and its catalytically essential histidine triad are highly conserved among other fuculose aldolases. Comparisons of structural features between GaFucA and its mesophilic and thermophilic homologues revealed that the enzyme has typical psychrophilic attributes, indicated by the presence of a high number of nonpolar residues at the surface and a lower number of arginine residues.
    Matched MeSH terms: Models, Molecular
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