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  1. Fulltext Preparation, Optimisation, and In Vitro Evaluation of [18F]AlF-NOTA-Pamidronic Acid for Bone Imaging PET
    Hassan H, Othman MF, Abdul Razak HR, Zakaria ZA, Ahmad Saad FF, Osman MA, et al.
    Molecules, 2022 Nov 17;27(22).
    PMID: 36432069 DOI: 10.3390/molecules27227969
    [18F]sodium fluoride ([18F]NaF) is recognised to be superior to [99mTc]-methyl diphosphate ([99mTc]Tc-MDP) and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) in bone imaging. However, there is concern that [18F]NaF uptake is not cancer-specific, leading to a higher number of false-positive interpretations. Therefore, in this work, [18F]AlF-NOTA-pamidronic acid was prepared, optimised, and tested for its in vitro uptake. NOTA-pamidronic acid was prepared by an N-Hydroxysuccinimide (NHS) ester strategy and validated by liquid chromatography-mass spectrometry analysis (LC-MS/MS). Radiolabeling of [18F]AlF-NOTA-pamidronic acid was optimised, and it was ensured that all quality control analysis requirements for the radiopharmaceuticals were met prior to the in vitro cell uptake studies. NOTA-pamidronic acid was successfully prepared and radiolabeled with 18F. The radiolabel was prepared in a 1:1 molar ratio of aluminium chloride (AlCl3) to NOTA-pamidronic acid and heated at 100 °C for 15 min in the presence of 50% ethanol (v/v), which proved to be optimal. The preliminary in vitro results of the binding of the hydroxyapatite showed that [18F]AlF-NOTA-pamidronic acid was as sensitive as [18F]sodium fluoride ([18F]NaF). Normal human osteoblast cell lines (hFOB 1.19) and human osteosarcoma cell lines (Saos-2) were used for the in vitro cellular uptake studies. It was found that [18F]NaF was higher in both cell lines, but [18F]AlF-NOTA-pamidronic acid showed promising cellular uptake in Saos-2. The preliminary results suggest that further preclinical studies of [18F]AlF-NOTA-pamidronic acid are needed before it is transferred to clinical research.
    Matched MeSH terms: Oligopeptides/chemistry
  2. Fulltext Pharmaceutical Potential of Casein-Derived Tripeptide Met-Lys-Pro: Improvement in Cognitive Impairments and Suppression of Inflammation in APP/PS1 Mice
    Matsuzaki Tada A, Hamezah HS, Pahrudin Arrozi A, Abu Bakar ZH, Yanagisawa D, Tooyama I
    J Alzheimers Dis, 2022;89(3):835-848.
    PMID: 35964178 DOI: 10.3233/JAD-220192
    BACKGROUND: Tripeptide Met-Lys-Pro (MKP), a component of casein hydrolysates, has effective angiotensin-converting enzyme (ACE) inhibitory activity. Brain angiotensin II enzyme activates the NADPH oxidase complex via angiotensin II receptor type 1 (AT1) and enhances oxidative stress injury. ACE inhibitors improved cognitive function in Alzheimer's disease (AD) mouse models and previous clinical trials. Thus, although undetermined, MKP may be effective against pathological amyloid-β (Aβ) accumulation-induced cognitive impairment.

    OBJECTIVE: The current study aimed to investigate the potential of MKP as a pharmaceutical against AD by examining MKP's effect on cognitive function and molecular changes in the brain using double transgenic (APP/PS1) mice.

    METHODS: Experimental procedures were conducted in APP/PS1 mice (n = 38) with a C57BL/6 background. A novel object recognition test was used to evaluate recognition memory. ELISA was used to measure insoluble Aβ40, Aβ42, and TNF-α levels in brain tissue. Immunohistochemical analysis allowed the assessment of glial cell activation in MKP-treated APP/PS1 mice.

    RESULTS: The novel object recognition test revealed that MKP-treated APP/PS1 mice showed significant improvement in recognition memory. ELISA of brain tissue showed that MKP significantly reduced insoluble Aβ40, Aβ42, and TNF-α levels. Immunohistochemical analysis indicated the suppression of the marker for microglia and reactive astrocytes in MKP-treated APP/PS1 mice.

    CONCLUSION: Based on these results, we consider that MKP could ameliorate pathological Aβ accumulation-induced cognitive impairment in APP/PS1 mice. Furthermore, our findings suggest that MKP potentially contributes to preventing cognitive decline in AD.

    Matched MeSH terms: Oligopeptides
  3. 18F-PSMA-1007 PET/CT for Initial Staging of Renal Cell Carcinoma in an End-Stage Renal Disease Patient
    Marafi F, Sasikumar A, Aldaas M, Esmail A
    Clin Nucl Med, 2021 Jan;46(1):e65-e67.
    PMID: 33181733 DOI: 10.1097/RLU.0000000000003354
    A 46-year-old man with end-stage renal disease and renal cell carcinoma underwent F-FDG PET/CT for initial staging followed by F-PSMA-1007 PET/CT. Unlike F-FDG, which undergoes renal clearance, F-PSMA-1007 undergoes hepatobiliary clearance and thus generates superior quality images. F-PSMA-1007 PET/CT showed intense tracer-avid left renal mass lesion (FDG nonavid); lytic bone lesions (FDG avid) and single liver lesion (FDG nonavid). This case highlights the superiority of F-PSMA-1007 over F-FDG PET/CT in identifying primary lesion as well as metastatic sites in case of renal cell carcinoma even in the presence of end-stage renal disease.
    Matched MeSH terms: Oligopeptides*
  4. Fulltext Design and Characterisation of Inhibitory Peptides against Bleg1_2478, an Evolutionary Divergent B3 Metallo-β-lactamase
    Selvaraju G, Leow TC, Salleh AB, Normi YM
    Molecules, 2020 Dec 09;25(24).
    PMID: 33316879 DOI: 10.3390/molecules25245797
    Previously, a hypothetical protein (HP) termed Bleg1_2437 (currently named Bleg1_2478) from Bacillus lehensis G1 was discovered to be an evolutionary divergent B3 subclass metallo-β-lactamase (MBL). Due to the scarcity of clinical inhibitors for B3 MBLs and the divergent nature of Bleg1_2478, this study aimed to design and characterise peptides as inhibitors against Bleg1_2478. Through in silico docking, RSWPWH and SSWWDR peptides with comparable binding energy to ampicillin were obtained. In vitro assay results showed RSWPWH and SSWWDR inhibited the activity of Bleg1_2478 by 50% at concentrations as low as 0.90 µM and 0.50 µM, respectively. At 10 µM of RSWPWH and 20 µM of SSWWDR, the activity of Bleg1_2478 was almost completely inhibited. Isothermal titration calorimetry (ITC) analyses showed slightly improved binding properties of the peptides compared to ampicillin. Docked peptide-protein complexes revealed that RSWPWH bound near the vicinity of the Bleg1_2478 active site while SSWWDR bound at the center of the active site itself. We postulate that the peptides caused the inhibition of Bleg1_2478 by reducing or blocking the accessibility of its active site from ampicillin, thus hampering its catalytic function.
    Matched MeSH terms: Oligopeptides/chemical synthesis*; Oligopeptides/pharmacology; Oligopeptides/chemistry*
  5. Fulltext Zerumbone Induces Apoptosis in Breast Cancer Cells by Targeting αvβ3 Integrin upon Co-Administration with TP5-iRGD Peptide
    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: Oligopeptides/administration & dosage; Oligopeptides/pharmacology*; Oligopeptides/chemistry
  6. Fulltext Purification and identification of novel cytotoxic oligopeptides from soft coral Sarcophyton glaucum
    Quah Y, Mohd Ismail NI, Ooi JLS, Affendi YA, Abd Manan F, Teh LK, et al.
    J Zhejiang Univ Sci B, 2019 1 8;20(1):59-70.
    PMID: 30614230 DOI: 10.1631/jzus.B1700586
    Globally, peptide-based anticancer therapies have drawn much attention. Marine organisms are a reservoir of anticancer peptides that await discovery. In this study, we aimed to identify cytotoxic oligopeptides from Sarcophyton glaucum. Peptides were purified from among the S. glaucum hydrolysates produced by alcalase, chymotrypsin, papain, and trypsin, guided by a methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay on the human cervical cancer (HeLa) cell line for cytotoxicity evaluation. Purification techniques adopted were membrane ultrafiltration, gel filtration chromatography, solid phase extraction (SPE), and reversed-phase high-performance liquid chromatography (RP-HPLC). Purified peptides were identified by de novo peptide sequencing. From papain hydrolysate, three peptide sequences were identified: AGAPGG, AERQ, and RDTQ (428.45, 502.53, and 518.53 Da, respectively). Peptides synthesized from these sequences exhibited cytotoxicity on HeLa cells with median effect concentration (EC50) values of 8.6, 4.9, and 5.6 mmol/L, respectively, up to 5.8-fold stronger than the anticancer drug 5-fluorouracil. When tested at their respective EC50, AGAPGG, AERQ, and RDTQ showed only 16%, 25%, and 11% cytotoxicity to non-cancerous Hek293 cells, respectively. In conclusion, AERQ, AGAPGG, and RDTQ are promising candidates for future development as peptide-based anticancer drugs.
    Matched MeSH terms: Oligopeptides
  7. A Cyclic Peptide Inhibitor of the iNOS-SPSB Protein-Protein Interaction as a Potential Anti-Infective Agent
    Sadek MM, Barlow N, Leung EWW, Williams-Noonan BJ, Yap BK, Shariff FM, et al.
    ACS Chem. Biol., 2018 10 19;13(10):2930-2938.
    PMID: 30226743 DOI: 10.1021/acschembio.8b00561
    SPRY domain- and SOCS box-containing proteins SPSB1, SPSB2, and SPSB4 interact with inducible nitric oxide synthase (iNOS), causing the iNOS to be polyubiquitinated and targeted for degradation. Inhibition of this interaction increases iNOS levels, and consequently cellular nitric oxide (NO) concentrations, and has been proposed as a potential strategy for killing intracellular pathogens. We previously described two DINNN-containing cyclic peptides (CP1 and CP2) as potent inhibitors of the murine SPSB-iNOS interaction. In this study, we report the crystal structures of human SPSB4 bound to CP1 and CP2 and human SPSB2 bound to CP2. We then used these structures to design a new inhibitor in which an intramolecular hydrogen bond was replaced with a hydrocarbon linkage to form a smaller macrocycle while maintaining the bound geometry of CP2 observed in the crystal structures. This resulting pentapeptide SPSB-iNOS inhibitor (CP3) has a reduced macrocycle ring size, fewer nonbinding residues, and includes additional conformational constraints. CP3 has a greater affinity for SBSB2 ( KD = 7 nM as determined by surface plasmon resonance) and strongly inhibits the SPSB2-iNOS interaction in macrophage cell lysates. We have also determined the crystal structure of CP3 in complex with human SPSB2, which reveals the structural basis for the increased potency of CP3 and validates the original design.
    Matched MeSH terms: Oligopeptides/pharmacology; Oligopeptides/chemistry*
  8. Activity behaviors in lean and morbidly obese pregnant women
    Fazzi C, Mohd-Shukri N, Denison FC, Saunders DH, Norman JE, Reynolds RM
    Scand J Med Sci Sports, 2018 Oct;28(10):2189-2195.
    PMID: 29772608 DOI: 10.1111/sms.13219
    Interventions to increase physical activity in pregnancy are challenging for morbidly obese women. Targeting sedentary behaviors may be a suitable alternative to increase energy expenditure. We aimed to determine total energy expenditure, and energy expended in sedentary activities in morbidly obese and lean pregnant women. We administered the Pregnancy Physical Activity Questionnaire (nonobjective) and the Actical accelerometer (objective) to morbidly obese (BMI ≥ 40 kg/m²) and lean (BMI ≤ 25 Kg/m²) pregnant women recruited in early (<24 weeks), and late (≥24 weeks) gestation. Data are mean (SD). Morbidly obese pregnant women reported expending significantly more energy per day in early (n = 140 vs 109; 3198.4 (1847.1) vs 1972.3 (10284.8) Kcal/d, P 
    Matched MeSH terms: Oligopeptides
  9. Two new Tytthoscincus Linkem, Diesmos, Brown (Squamata; Scincidae) from Peninsular Malaysia and another case of microsyntopy between ecologically specialized, unrelated, leaf-litter species
    Grismer LL, Wood PLJ, Ahmad AB, Baizul-Hafsyam BS, Afiq-Shuhaimi M, Rizal SA, et al.
    Zootaxa, 2018 May 29;4425(1):87-107.
    PMID: 30313468 DOI: 10.11646/zootaxa.4425.1.5
    Two new species of diminutive, sympatric, lowland, leaf-litter skinks of the genus Tytthoscincus Linkem, Diesmos Brown from the Sekayu region of Hulu Terengganu, Terengganu State in northeastern Peninsular Malaysia are described on the basis genetic and morphological data. One of the new species, T. monticolus sp. nov., was collected in a hilly riparian area along Sungai (=river) Bubu and is most closely related to an undescribed species from the Tembak Reservoir area. The other, T. keciktuek sp. nov. collected along Sungai Peres, is most closely related to T. perhentianensis Grismer, Wood, Grismer from Pulau (=island) Perhentian Besar. Sympatry and syntopy of multiple, specialized, unrelated, leaf-litter species of Tytthoscincus was previously only known from upland areas and these new species represent the first example of lowland of sympatry. More importantly, however, these endemic species add to a growing body of research and discoveries that continue to underscore the unrealized biodiversity of the riparian systems of Hulu Terengganu and the Sekayu region and their need for protection and continued study.
    Matched MeSH terms: Oligopeptides
  10. Fulltext Xeno-free culture of human pluripotent stem cells on oligopeptide-grafted hydrogels with various molecular designs
    Chen YM, Chen LH, Li MP, Li HF, Higuchi A, Kumar SS, et al.
    Sci Rep, 2017 03 23;7:45146.
    PMID: 28332572 DOI: 10.1038/srep45146
    Establishing cultures of human embryonic (ES) and induced pluripotent (iPS) stem cells in xeno-free conditions is essential for producing clinical-grade cells. Development of cell culture biomaterials for human ES and iPS cells is critical for this purpose. We designed several structures of oligopeptide-grafted poly (vinyl alcohol-co-itaconic acid) hydrogels with optimal elasticity, and prepared them in formations of single chain, single chain with joint segment, dual chain with joint segment, and branched-type chain. Oligopeptide sequences were selected from integrin- and glycosaminoglycan-binding domains of the extracellular matrix. The hydrogels grafted with vitronectin-derived oligopeptides having a joint segment or a dual chain, which has a storage modulus of 25 kPa, supported the long-term culture of human ES and iPS cells for over 10 passages. The dual chain and/or joint segment with cell adhesion molecules on the hydrogels facilitated the proliferation and pluripotency of human ES and iPS cells.
    Matched MeSH terms: Oligopeptides/metabolism*
  11. Screening and identification of five peptides from pinto bean with inhibitory activities against α-amylase using phage display technique
    Ngoh YY, Lim TS, Gan CY
    Enzyme Microb Technol, 2016 Jul;89:76-84.
    PMID: 27233130 DOI: 10.1016/j.enzmictec.2016.04.001
    The objective of this study was to screen and identify α-amylase inhibitor peptides from Pinto bean. Five Pinto bean bioactive peptides were successfully identified: PPHMLP (P1), PLPWGAGF (P3), PPHMGGP (P6), PLPLHMLP (P7) and LSSLEMGSLGALFVCM (P9). Based on ELISA results, their promising optical density values were 1.27; 3.71, 1.67, 3.20 and 1.03, respectively, which indicated the binding interaction between the peptide and α-amylase occurred. The highest inhibitory activity (66.72%) of the chemically synthesized peptide was shown in SyP9 followed by SyP1 (48.86%), SyP3 (31.17%), SyP7 (27.88%) and SyP6 (23.96%). The IC50 values were 1.97, 8.96, 14.63, 18.45 and 20.56mgml(-1), respectively. Structure activity relationship study revealed that α-amylase was inhibited due to its residues of Ala230, Asp229, Asp326, Tyr54, Met195, Leu194 and His233 were bound. On the other hand, the residues of PBBP (i.e. histidine, proline and methionine) were found to have the highest potency in the binding interaction.
    Matched MeSH terms: Oligopeptides/genetics; Oligopeptides/pharmacology; Oligopeptides/chemistry
  12. Fulltext Cloning, expression, purification, crystallization and X-ray crystallographic analysis of recombinant human C1ORF123 protein
    Rahaman SN, Mat Yusop J, Mohamed-Hussein ZA, Ho KL, Teh AH, Waterman J, et al.
    Acta Crystallogr F Struct Biol Commun, 2016 Mar;72(Pt 3):207-13.
    PMID: 26919524 DOI: 10.1107/S2053230X16002016
    C1ORF123 is a human hypothetical protein found in open reading frame 123 of chromosome 1. The protein belongs to the DUF866 protein family comprising eukaryote-conserved proteins with unknown function. Recent proteomic and bioinformatic analyses identified the presence of C1ORF123 in brain, frontal cortex and synapses, as well as its involvement in endocrine function and polycystic ovary syndrome (PCOS), indicating the importance of its biological role. In order to provide a better understanding of the biological function of the human C1ORF123 protein, the characterization and analysis of recombinant C1ORF123 (rC1ORF123), including overexpression and purification, verification by mass spectrometry and a Western blot using anti-C1ORF123 antibodies, crystallization and X-ray diffraction analysis of the protein crystals, are reported here. The rC1ORF123 protein was crystallized by the hanging-drop vapor-diffusion method with a reservoir solution comprised of 20% PEG 3350, 0.2 M magnesium chloride hexahydrate, 0.1 M sodium citrate pH 6.5. The crystals diffracted to 1.9 Å resolution and belonged to an orthorhombic space group with unit-cell parameters a = 59.32, b = 65.35, c = 95.05 Å. The calculated Matthews coefficient (VM) value of 2.27 Å(3) Da(-1) suggests that there are two molecules per asymmetric unit, with an estimated solvent content of 45.7%.
    Matched MeSH terms: Oligopeptides/chemistry
  13. Continuous harvest of stem cells via partial detachment from thermoresponsive nanobrush surfaces
    Peng IC, Yeh CC, Lu YT, Muduli S, Ling QD, Alarfaj AA, et al.
    Biomaterials, 2016 Jan;76:76-86.
    PMID: 26519650 DOI: 10.1016/j.biomaterials.2015.10.039
    Stem cell culture is typically based on batch-type culture, which is laborious and expensive. Here, we propose a continuous harvest method for stem cells cultured on thermoresponsive nanobrush surfaces. In this method, stem cells are partially detached from the nanobrush surface by reducing the temperature of the culture medium below the critical solution temperature needed for thermoresponse. The detached stem cells are harvested by exchange into fresh culture medium. Following this, the remaining cells are continuously cultured by expansion in fresh culture medium at 37 °C. Thermoresponsive nanobrush surfaces were prepared by coating block copolymers containing polystyrene (for hydrophobic anchoring onto culture dishes) with three types of polymers: (a) polyacrylic acid with cell-binding oligopeptides, (b) thermoresponsive poly-N-isopropylacrylamide, and (c) hydrophilic poly(ethyleneglycol)methacrylate. The optimal coating durations and compositions for these copolymers to facilitate adequate attachment and detachment of human adipose-derived stem cells (hADSCs) and embryonic stem cells (hESCs) were determined. hADSCs and hESCs were continuously harvested for 5 and 3 cycles, respectively, via the partial detachment of cells from thermoresponsive nanobrush surfaces.
    Matched MeSH terms: Oligopeptides
  14. Fulltext Efficacy of second-line antiretroviral therapy among people living with HIV/AIDS in Asia: results from the TREAT Asia HIV observational database
    Boettiger DC, Nguyen VK, Durier N, Bui HV, Heng Sim BL, Azwa I, et al.
    J Acquir Immune Defic Syndr, 2015 Feb 01;68(2):186-95.
    PMID: 25590271 DOI: 10.1097/QAI.0000000000000411
    BACKGROUND: Roughly 4% of the 1.25 million patients on antiretroviral therapy (ART) in Asia are using second-line therapy. To maximize patient benefit and regional resources, it is important to optimize the timing of second-line ART initiation and use the most effective compounds available.

    METHODS: HIV-positive patients enrolled in the TREAT Asia HIV Observational Database who had used second-line ART for ≥6 months were included. ART use and rates and predictors of second-line treatment failure were evaluated.

    RESULTS: There were 302 eligible patients. Most were male (76.5%) and exposed to HIV via heterosexual contact (71.5%). Median age at second-line initiation was 39.2 years, median CD4 cell count was 146 cells per cubic millimeter, and median HIV viral load was 16,224 copies per milliliter. Patients started second-line ART before 2007 (n = 105), 2007-2010 (n = 147) and after 2010 (n = 50). Ritonavir-boosted lopinavir and atazanavir accounted for the majority of protease inhibitor use after 2006. Median follow-up time on second-line therapy was 2.3 years. The rates of treatment failure and mortality per 100 patient/years were 8.8 (95% confidence interval: 7.1 to 10.9) and 1.1 (95% confidence interval: 0.6 to 1.9), respectively. Older age, high baseline viral load, and use of a protease inhibitor other than lopinavir or atazanavir were associated with a significantly shorter time to second-line failure.

    CONCLUSIONS: Increased access to viral load monitoring to facilitate early detection of first-line ART failure and subsequent treatment switch is important for maximizing the durability of second-line therapy in Asia. Although second-line ART is highly effective in the region, the reported rate of failure emphasizes the need for third-line ART in a small portion of patients.

    Matched MeSH terms: Oligopeptides/therapeutic use
  15. Design and synthesis of mono and bicyclic tetrapeptides thioester as potent inhibitor of histone deacetylases
    Hoque MA, Islam MS, Islam MN, Kato T, Nishino N, Ito A, et al.
    Amino Acids, 2014 Oct;46(10):2435-44.
    PMID: 25048030 DOI: 10.1007/s00726-014-1800-5
    Inhibitors of histone deacetylases (HDACs) are a promising class of anticancer agents that have an effect on gene regulation. The naturally occurring cyclic depsipeptide FK228 containing disulfide and Largazole possessing thioester functionalities act as pro-drugs and share the same HDAC inhibition mechanism in cell. Inspired from these facts, we have reported bicyclic tetrapeptide disulfide HDAC inhibitors resembling FK228 with potent activity and enhanced selectivity. In the present study, we report the design and synthesis of several mono and bicyclic tetrapeptide thioester HDAC inhibitors that share the inhibition mechanism similar to Largazole. Most of the compounds showed HDAC1 and HDAC4 inhibition and p21 promoting activity in nanomolar ranges. Among these the monocyclic peptides 1, 2 and bicyclic peptide, 4 are notable demanding more advanced research to be promising anticancer drug candidates.
    Matched MeSH terms: Oligopeptides/chemical synthesis*; Oligopeptides/pharmacology; Oligopeptides/chemistry
  16. Various polar tripeptides as asymmetric organocatalyst in direct aldol reactions in aqueous media
    Bayat S, Tejo BA, Salleh AB, Abdmalek E, Normi YM, Abdul Rahman MB
    Chirality, 2013 Nov;25(11):726-34.
    PMID: 23966316 DOI: 10.1002/chir.22205
    A series of tripeptide organocatalysts containing a secondary amine group and two amino acids with polar side chain units were developed and evaluated in the direct asymmetric intermolecular aldol reaction of 4-nitrobenzaldehyde and cyclohexanone. The effectiveness of short polar peptides as asymmetric catalysts in aldol reactions to attain high yields of enantio- and diastereoselective isomers were investigated. In a comparison, glutamic acid and histidine produced higher % ee and yields when they were applied as the second amino acid in short trimeric peptides. These short polar peptides were found to be efficient organocatalysts for the asymmetric aldol addition reaction in aqueous media.
    Matched MeSH terms: Oligopeptides/chemistry*
  17. Regulation of ITAM adaptor molecules and their receptors by inhibition of calcineurin-NFAT signalling during late stage osteoclast differentiation
    Zawawi MS, Dharmapatni AA, Cantley MD, McHugh KP, Haynes DR, Crotti TN
    Biochem Biophys Res Commun, 2012 Oct 19;427(2):404-9.
    PMID: 23000414 DOI: 10.1016/j.bbrc.2012.09.077
    Osteoclasts are specialised bone resorptive cells responsible for both physiological and pathological bone loss. Osteoclast differentiation and activity is dependent upon receptor activator NF-kappa-B ligand (RANKL) interacting with its receptor RANK to induce the transcription factor, nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1). The immunoreceptor tyrosine-based activation motif (ITAM)-dependent pathway has been identified as a co-stimulatory pathway in osteoclasts. Osteoclast-associated receptor (OSCAR) and triggering receptor expressed in myeloid cells (TREM2) are essential receptors that pair with adaptor molecules Fc receptor common gamma chain (FcRγ) and DNAX-activating protein 12kDa (DAP12) respectively to induce calcium signalling. Treatment with calcineurin-NFAT inhibitors, Tacrolimus (FK506) and the 11R-VIVIT (VIVIT) peptide, reduces NFATc1 expression consistent with a reduction in osteoclast differentiation and activity. This study aimed to investigate the effects of inhibiting calcineurin-NFAT signalling on the expression of ITAM factors and late stage osteoclast genes including cathepsin K (CathK), Beta 3 integrin (β3) and Annexin VIII (AnnVIII). Human peripheral blood mononuclear cells (PBMCs) were differentiated with RANKL and macrophage-colony stimulating factor (M-CSF) over 10days in the presence or absence of FK506 or VIVIT. Osteoclast formation (as assessed by tartrate resistant acid phosphatase (TRAP)) and activity (assessed by dentine pit resorption) were significantly reduced with treatment. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis demonstrated that FK506 treatment significantly (p<0.05) reduced the expression of NFATc1, CathK, OSCAR, FcRγ, TREM2 and DAP12 during the terminal stage of osteoclast formation. VIVIT treatment significantly (p<0.05) decreased CathK, OSCAR, FcRγ, and AnnVIII, gene expression. This data suggest FK506 and VIVIT act differently in targeting the calcineurin-NFAT signalling cascade to suppress key mediators of the ITAM pathway during late stage osteoclast differentiation and this is associated with a reduction in both osteoclast differentiation and activity.
    Matched MeSH terms: Oligopeptides/pharmacology
  18. Fulltext Residual effects of TMOF-Bti formulations against 1(st) instar Aedes aegypti Linnaeus larvae outside laboratory
    Saiful AN, Lau MS, Sulaiman S, Hidayatulfathi O
    Asian Pac J Trop Biomed, 2012 Apr;2(4):315-9.
    PMID: 23569922 DOI: 10.1016/S2221-1691(12)60031-8
    To evaluate the effectiveness and residual effects of trypsin modulating oostatic factor-Bacillus thuringiensis israeliensis (TMOF-Bti) formulations against Aedes aegypti (Ae. aegypti) (L.) larvae at UKM Campus Kuala Lumpur.
    Matched MeSH terms: Oligopeptides/pharmacology*
  19. Fulltext Comparative study of Mg/Al- and Zn/Al-layered double hydroxide-perindopril erbumine nanocomposites for inhibition of angiotensin-converting enzyme
    Hussein Al Ali SH, Al-Qubaisi M, Hussein MZ, Ismail M, Zainal Z, Hakim MN
    Int J Nanomedicine, 2012;7:4251-62.
    PMID: 22904631 DOI: 10.2147/IJN.S32267
    The intercalation of a drug active, perindopril, into Mg/Al-layered double hydroxide for the formation of a new nanocomposite, PMAE, was accomplished using a simple ion exchange technique. A relatively high loading percentage of perindopril of about 36.5% (w/w) indicates that intercalation of the active took place in the Mg/Al inorganic interlayer. Intercalation was further supported by Fourier transform infrared spectroscopy, and thermal analysis shows markedly enhanced thermal stability of the active. The release of perindopril from the nanocomposite occurred in a controlled manner governed by pseudo-second order kinetics. MTT assay showed no cytotoxicity effects from either Mg/Al-layered double hydroxide or its nanocomposite, PMAE. Mg/Al-layered double hydroxide showed angiotensin-converting enzyme inhibitory activity, with 5.6% inhibition after 90 minutes of incubation. On incubation of angiotensin-converting enzyme with 0.5 μg/mL of the PMAE nanocomposite, inhibition of the enzyme increased from 56.6% to 70.6% at 30 and 90 minutes, respectively. These results are comparable with data reported in the literature for Zn/Al-perindopril.
    Matched MeSH terms: Oligopeptides/analysis; Oligopeptides/metabolism
  20. Fulltext Inhibition of enterovirus 71 (EV-71) infections by a novel antiviral peptide derived from EV-71 capsid protein VP1
    Tan CW, Chan YF, Sim KM, Tan EL, Poh CL
    PLoS One, 2012;7(5):e34589.
    PMID: 22563456 DOI: 10.1371/journal.pone.0034589
    Enterovirus 71 (EV-71) is the main causative agent of hand, foot and mouth disease (HFMD). In recent years, EV-71 infections were reported to cause high fatalities and severe neurological complications in Asia. Currently, no effective antiviral or vaccine is available to treat or prevent EV-71 infection. In this study, we have discovered a synthetic peptide which could be developed as a potential antiviral for inhibition of EV-71. Ninety five synthetic peptides (15-mers) overlapping the entire EV-71 capsid protein, VP1, were chemically synthesized and tested for antiviral properties against EV-71 in human Rhabdomyosarcoma (RD) cells. One peptide, SP40, was found to significantly reduce cytopathic effects of all representative EV-71 strains from genotypes A, B and C tested, with IC(50) values ranging from 6-9.3 µM in RD cells. The in vitro inhibitory effect of SP40 exhibited a dose dependent concentration corresponding to a decrease in infectious viral particles, total viral RNA and the levels of VP1 protein. The antiviral activity of SP40 peptide was not restricted to a specific cell line as inhibition of EV-71 was observed in RD, HeLa, HT-29 and Vero cells. Besides inhibition of EV-71, it also had antiviral activities against CV-A16 and poliovirus type 1 in cell culture. Mechanism of action studies suggested that the SP40 peptide was not virucidal but was able to block viral attachment to the RD cells. Substitutions of arginine and lysine residues with alanine in the SP40 peptide at positions R3A, R4A, K5A and R13A were found to significantly decrease antiviral activities, implying the importance of positively charged amino acids for the antiviral activities. The data demonstrated the potential and feasibility of SP40 as a broad spectrum antiviral agent against EV-71.
    Matched MeSH terms: Oligopeptides/chemical synthesis; Oligopeptides/genetics; Oligopeptides/pharmacology*
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