Structural Aspects of Salivary Glycoproteins

1987 ◽  
Vol 66 (2) ◽  
pp. 436-441 ◽  
Author(s):  
M.J. Levine ◽  
M.S. Reddy ◽  
L.A. Tabak ◽  
R.E. Loomis ◽  
E.J. Bergey ◽  
...  
Keyword(s):  
Peptide Chain ◽  
Random Coil ◽  
Oral Streptococci ◽  
Synthetic Hydroxyapatite ◽  
Covalently Linked ◽  
Human Parotid Saliva ◽  
Oral Ecology ◽  
Structural Aspects ◽  
Single Peptide

The protective functions of saliva are attributed, in part, to its serous and mucous glycoproteins. We have studied, as representative molecules, the proline-rich glycoprotein (PRG) from human parotid saliva and the high (MGI ) and low (MG2) molecular weight mucins from submandibular-sublingual saliva. PRG (38.9 kDa) contains 40% carbohydrate consisting of 6 triantennary N-linked units and a single peptide chain of 231 amino acids, 75% of which = PRO+GLY+GLN. PRG's secondary structure is comprised of 70% random coil (naked regions) and 30% β-turns (glycosylated domains). MGI (>103 kDa) contains 15% protein (several disulfide linked subunits), 78% carbohydrate (290 units of 4-16 residues), 7% sulfate, and small amounts of covalently linked fatty acids. MG2 (200-250 kDa) contains 30% protein (single peptide chain), 68% carbohydrate (170 units of 2-7 residues), and 2% sulfate. The major carbohydrate units of MG2 are: NeuAcα2, 3Galβ1, 3GalNAc, Galβ1, 3GalNAc, and Fucα1, 2Galβ1, 3GalNAc. MG1 contains hydrophobic domains, as evidenced by its ability to bind fluorescent hydrophobic probes; MG2 does not. Collectively, the biochemical and biophysical comparisons between MGI and MG2 indicate that these two mucins are structurally different. Several functional properties of MG1, MG2, and PRG have been examined, including their presence in two-hour in vivo enamel pellicle, binding to synthetic hydroxyapatite, lubricating properties, and interactions with oral streptococci. The data presented suggest that these glycoproteins may have multiple functions which are predicated, in part, on their carbohydrate units. The potential significance of the structure-function relationships of these glycoproteins to the oral ecology is discussed.

Conjugates of Classical DNA/RNA Binder with Nucleobase: Chemical, Biochemical and Biomedical Applications

2019 ◽  
Vol 26 (30) ◽  
pp. 5609-5624
Author(s):  
Dijana Saftić ◽  
Željka Ban ◽  
Josipa Matić ◽  
Lidija-Marija Tumirv ◽  
Ivo Piantanida
Keyword(s):  
Molecular Weight ◽  
Small Molecules ◽  
Biomedical Applications ◽  
Protein Targets ◽  
New Class ◽  
Rna Targets ◽  
Covalently Linked ◽  
Structural Aspects

: Among the most intensively studied classes of small molecules (molecular weight < 650) in biomedical research are small molecules that non-covalently bind to DNA/RNA, and another intensively studied class is nucleobase derivatives. Both classes have been intensively elaborated in many books and reviews. However, conjugates consisting of DNA/RNA binder covalently linked to nucleobase are much less studied and have not been reviewed in the last two decades. Therefore, this review summarized reports on the design of classical DNA/RNA binder – nucleobase conjugates, as well as data about their interactions with various DNA or RNA targets, and even in some cases protein targets are involved. According to these data, the most important structural aspects of selective or even specific recognition between small molecule and target are proposed, and where possible related biochemical and biomedical aspects were discussed. The general conclusion is that this, rather new class of molecules showed an amazing set of recognition tools for numerous DNA or RNA targets in the last two decades, as well as few intriguing in vitro and in vivo selectivities. Several lead research lines show promising advancements toward either novel, highly selective markers or bioactive, potentially druggable molecules.

scholarly journals Synthesis and Two-Dimensional 1Η and 13C NMR Investigations of an Inhibitor of Hematopoietic Stem Cell Proliferation Ac–Ser–Asp–Lys–Pro–OH

1992 ◽  
Vol 47 (9) ◽  
pp. 1324-1332 ◽  
Author(s):  
Jens Freund ◽  
Afroditi Kapurniotu ◽  
Tadeusz A. Holak ◽  
Maryse Lenfant ◽  
Wolfgang Voelter
Keyword(s):  
Cell Proliferation ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Solid Phase ◽  
Water Solution ◽  
Random Coil ◽  
Hematopoietic Stem ◽  
Stem Cell Proliferation ◽  
Equilibrium Ratio

The solid phase synthesis of the inhibitor of hematopoietic stem cell proliferation, Ac–Ser–Asp–Lys–Pro–OH, and its derivative Ac–Ala–Asp–Lys–Pro–OH is described. 1H and 13C NMR investigations demonstrate that both peptides show no prefered conformation in water solution. Both peptides exist in a Pro-cis-trans equilibrium ratio of 9 (trans) : 1 (cis). Thymosin β4 is believed to be the precursor molecule of the tetrapeptide Ac–SDKP. The attachement of the random coil tetrapeptide to a rigid helical fragment could facilitate its in vivo enzymatic cleavage.

The C-terminal sequence of amino acid residues of κ-casein isolated from buffalo's milk

1967 ◽  
Vol 34 (1) ◽  
pp. 85-88 ◽  
Author(s):  
M. H. Abd El-Salam ◽  
W. Manson
Keyword(s):  
Amino Acids ◽  
Molecular Weight ◽  
Amino Acid ◽  
Peptide Chain ◽  
Amino Acid Residues ◽  
Terminal Sequence ◽  
Carboxypeptidase A ◽  
Phosphorous Content ◽  
Single Peptide

SummaryWhen κ-casein from buffalo's milk was treated with carboxypeptidase A (EC 3. 4. 2. 1),4 amino acids, valine, threonine, serine and alanine were released from the protein in a manner consistent with the view that they originate in the C-terminal sequence of a single peptide chain. The amounts produced suggest a minimum molecular weight for buffalo κ-casein of approximately 17000, in agreement with the value calculated from the phosphorous content on the basis of the presence of 2 phosphorus atoms/molecule. A comparison is made with the C-terminal sequence reported for bovine κ-casein.

scholarly journals THE EFFECT OF ESSENTIAL OILS ON MICROORGANISMS CAUSING CARIES AND PERIODONTITIS

2020 ◽  
Vol 20 (2) ◽  
pp. 253-259
Author(s):  
N.M. Devyatkina ◽  
N.O. Bobrova ◽  
E.M. Vazhnichaya
Keyword(s):  
Essential Oils ◽  
Dental Treatment ◽  
Therapeutic Potential ◽  
Oral Care ◽  
Antibacterial Properties ◽  
Herbal Medicines ◽  
Oral Streptococci ◽  
Tea Tree

The oral cavity contains a large number of bacteria, some of which are involved in the development of caries and periodontitis (S. mutans, S. sobrinus, Lactobacilli spp, P. intermedia, P. gingivalis, and T. forythus). The disadvantages of existing antiseptics used in dentistry necessitate the study of antibacterial properties of herbal medicines, and, in particular, of essential oils. The aim of this review is to provide the analysis of literature sources from PubMed and Google Scholar databases related to the effects of essential oils of cloves, mint, thyme, eucalyptus, tea tree and their components on cariogenic and periodontopathic microflora. It was found out that the most in vitro studies evaluated the effects of essential oils or isolated compounds (eugenol, menthol, thymol, carvacrol, eucalyptol, and terpinene-4-ol) on S. mutans, which is considered to be the most cariogenic of oral streptococci, and the researchers limited to defining the susceptibility of the microorganism and effects on biofilm formation. Only in a few studies, the effects of essential oils on the virulence factors of oral pathogens, in particular glycosyl transferase, are represented. Clinical trials of essential oils, their components and combinations confirm the therapeutic potential of these agents in vivo, but raise the question of their effectiveness, taking into account the short-term action, which does not exceed the potency of chlorhexidine. Essential oils of cloves, mint, thyme, eucalyptus, tea tree and their components should be used for treating caries and periodontitis. They are also promising when used as agents of the oral care products, preservatives of the dental medicinal forms, and as remedies for halitosis. With a rational prescription, essential oils can be useful in improving the quality of dental treatment and preventive procedures.

Compositional, Structural, and Kinetic Aspects of Lipid Digestion and Bioavailability: In Vitro, In Vivo, and Modeling Approaches

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Sébastien Marze
Keyword(s):  
Annual Review ◽  
Publication Date ◽  
Lipid Digestion ◽  
Modeling Approaches ◽  
Digestion Kinetics ◽  
Food Design ◽  
Structural Aspects ◽  
Development And Evolution

Lipid digestion and bioavailability are usually investigated separately, using different approaches (in vitro, modeling, in vivo). However, a few inclusive studies show that their kinetics are closely linked. Lipid bioavailability kinetics is likely involved in the development and evolution of several diseases, so lipid digestion kinetics could be involved as well and can be modulated by food design or combination. To illustrate this possibility, the compositional and structural aspects of lipid digestion kinetics, as investigated using in vitro and modeling approaches, are presented first. Then, in vivo and mixed approaches enabling the study of both kinetics are reviewed and discussed. Finally, disparate modeling approaches are introduced, and a unifying modeling scheme is proposed, opening new perspectives for understanding the role and interactions of various factors (chemical, physical, and biological) involved in lipid metabolism. Expected final online publication date for the Annual Review of Food Science and Technology, Volume 13 is March 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals From Beyond the Pale to the Pale Riders: The Emerging Association of Bacteria with Oral Cancer

2020 ◽  
Vol 99 (6) ◽  
pp. 604-612 ◽  
Author(s):  
Z.R. Fitzsimonds ◽  
C.J. Rodriguez-Hernandez ◽  
J. Bagaitkar ◽  
R.J. Lamont
Keyword(s):  
Oral Cancer ◽  
Epithelial Cells ◽  
Periodontal Disease ◽  
Bacterial Communities ◽  
Epithelial To Mesenchymal Transition ◽  
Driver Mutations ◽  
Oral Streptococci ◽  
Periodontal Pathogens ◽  
Mesenchymal Transition

Oral cancer, predominantly oral squamous cell carcinoma (OSCC), is the eighth-most common cancer worldwide, with a 5-y survival rate <50%. There are numerous risk factors for oral cancer, among which periodontal disease is gaining increasing recognition. The creation of a sustained dysbiotic proinflammatory environment by periodontal bacteria may serve to functionally link periodontal disease and oral cancer. Moreover, traditional periodontal pathogens, such as Porphyromonas gingivalis, Fusobacterium nucleatum, and Treponema denticola, are among the species most frequently identified as being enriched in OSCC, and they possess a number of oncogenic properties. These organisms share the ability to attach and invade oral epithelial cells, and from there each undergoes its own unique molecular dialogue with the host epithelium, which ultimately converges on acquired phenotypes associated with cancer, including inhibition of apoptosis, increased proliferation, and activation of epithelial-to-mesenchymal transition leading to increased migration of epithelial cells. Additionally, emerging properties of structured bacterial communities may increase oncogenic potential, and consortia of P. gingivalis and F. nucleatum are synergistically pathogenic within in vivo oral cancer models. Interestingly, however, some species of oral streptococci can antagonize the phenotypes induced by P. gingivalis, indicating functionally specialized roles for bacteria in oncogenic communities. Transcriptomic data support the concept that functional, rather than compositional, properties of oral bacterial communities have more relevance to cancer development. Collectively, the evidence is consistent with a modified polymicrobial synergy and dysbiosis model for bacterial involvement in OSCC, with driver mutations generating a conducive microenvironment on the epithelial boundary, which becomes further dysbiotic by the synergistic action of bacterial communities.

scholarly journals Understanding the Role of Shape and Composition of Star-Shaped Polymers and their Ability to Both Bind and Prevent Bacteria Attachment on Oral Relevant Surfaces

2019 ◽  
Vol 10 (4) ◽  
pp. 56 ◽  
Author(s):  
Hamid Mortazavian ◽  
Guillaume A. Picquet ◽  
Jānis Lejnieks ◽  
Lynette A. Zaidel ◽  
Carl P. Myers ◽  
...  
Keyword(s):  
Bacterial Adhesion ◽  
Oral Care ◽  
Oral Bacteria ◽  
New Material ◽  
Polymer Shape ◽  
Dental Applications ◽  
Insight Into ◽  
Structural Aspects

In this study, we have prepared a series of 4- and 6-arm star-shaped polymers with varying molecular weight and hydrophobicity in order to provide insight into the role and relationship that shape and composition have on the binding and protecting of oral relevant surfaces (hydroxyapatite, HAP) from bacteria colonization. Star-shaped acrylic acid polymers were prepared by free-radical polymerization in the presence of chain transfer agents with thiol groups, and their binding to the HAP surfaces and subsequent bacteria repulsion was measured. We observed that binding was dependent on both polymer shape and hydrophobicity (star vs. linear), but their relative efficacy to reduce oral bacteria attachment from surfaces was dependent on their hydrophobicity only. We further measured the macroscopic effects of these materials to modify the mucin-coated HAP surfaces through contact angle experiments; the degree of angle change was dependent on the relative hydrophobicity of the materials suggesting future in vivo efficacy. The results from this study highlight that star-shaped polymers represent a new material platform for the development of dental applications to control bacterial adhesion which can lead to tooth decay, with various compositional and structural aspects of materials being vital to effectively design oral care products.

scholarly journals Synthetic Covalently Linked Dimeric Form of H2 Relaxin Retains Native RXFP1 Activity and Has ImprovedIn VitroSerum Stability

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Vinojini B. Nair ◽  
Ross A. D. Bathgate ◽  
Frances Separovic ◽  
Chrishan S. Samuel ◽  
Mohammed Akhter Hossain ◽  
...  
Keyword(s):  
Half Life ◽  
Solid Phase ◽  
Phase Iii ◽  
Phase Iii Clinical Trials ◽  
H2 Relaxin ◽  
Covalent Dimer ◽  
Dimeric Form ◽  
Covalently Linked ◽  
G Protein Coupled

Human (H2) relaxin is a two-chain peptide member of the insulin superfamily and possesses potent pleiotropic roles including regulation of connective tissue remodeling and systemic and renal vasodilation. These effects are mediated through interaction with its cognate G-protein-coupled receptor, RXFP1. H2 relaxin recently passed Phase III clinical trials for the treatment of congestive heart failure. However, itsin vivohalf-life is short due to its susceptibility to proteolytic degradation and renal clearance. To increase its residence time, a covalent dimer of H2 relaxin was designed and assembled through solid phase synthesis of the two chains, including a judiciously monoalkyne sited B-chain, followed by their combination through regioselective disulfide bond formation. Use of a bisazido PEG7linker and “click” chemistry afforded a dimeric H2 relaxin with its active site structurally unhindered. The resulting peptide possessed a similar secondary structure to the native monomeric H2 relaxin and bound to and activated RXFP1 equally well. It had fewer propensities to activate RXFP2, the receptor for the related insulin-like peptide 3. In human serum, the dimer had a modestly increased half-life compared to the monomeric H2 relaxin suggesting that additional oligomerization may be a viable strategy for producing longer acting variants of H2 relaxin.

scholarly journals Diagnosis of Maroteaux—Lamy syndrome by the use of radiolabelled oligosaccharides as substrates for the determination of arylsulphatase B activity

1986 ◽  
Vol 234 (3) ◽  
pp. 507-514 ◽  
Author(s):  
J J Hopwood ◽  
H Elliott ◽  
V J Muller ◽  
G T P Saccone
Keyword(s):  
Glucuronic Acid ◽  
Specific Substrate ◽  
Natural Substrate ◽  
Dermatan Sulphate ◽  
Cultured Skin ◽  
Normal Controls ◽  
Structural Aspects ◽  
Physiological Substrates

The kinetic parameters (Km and V) of human arylsulphatase B (4-sulpho-N-acetylgalactosamine sulphatase) activity in cultured skin fibroblasts were determined with a variety of substrates matching structural aspects of the physiological substrates in vivo chondroitin 4-sulphate and dermatan sulphate. More structurally complex substrates, in which several aspects of the aglycone structure of the natural substrate were maintained, were desulphated up to 4400 times faster than the minimum arylsulphatase-B-specific substrate, namely the monosaccharide N-acetylgalactosamine 4-sulphate. Aglycone structures that influence substrate binding and/or enzyme activity were an adjacent-residue C-6 carboxy group and a second but internal N-acetylgalactosamine 4-sulphate residue. Arylsulphatase B activity in fibroblast homogenates assayed with O-(beta-N-acetylgalactosamine 4-sulphate)-(1→)-O-D-(beta-glucuronic acid)-(1→3)-O-D-N-acetyl[1-3H] galactosaminitol 4-sulphate derived from chondroitin 4-sulphate as substrate clearly distinguished Maroteaux-Lamy-syndrome patients from normal controls and other mucopolysaccharidosis patients. We recommend the use of the above trisaccharide substrate for both postnatal and prenatal diagnosis of Maroteaux-Lamy syndrome.

Interactions of heparin and a covalently-linked antithrombin-heparin complex with components of the fibrinolytic system

2013 ◽  
Vol 110 (12) ◽  
pp. 1180-1188 ◽  
Author(s):  
Ankush Chander ◽  
Helen M. Atkinson ◽  
Ivan Stevic ◽  
Leslie R. Berry ◽  
Paul Y. Kim ◽  
...  
Keyword(s):  
Thrombolytic Therapy ◽  
Unfractionated Heparin ◽  
Anticoagulant Therapy ◽  
Coagulation Factors ◽  
Order Rate Constant ◽  
Fibrinolytic System ◽  
Clot Lysis ◽  
Covalently Linked ◽  
Fibrinolytic Potential

SummaryUnfractionated heparin (UFH) is used as an adjunct during thrombolytic therapy. However, its use is associated with limitations, such as the inability to inhibit surface bound coagulation factors. We have developed a covalent conjugate of antithrombin (AT) and heparin (ATH) with superior anticoagulant properties compared with UFH. Advantages of ATH include enhanced inhibition of surface-bound coagulation enzymes and the ability to reduce the overall size and mass of clots in vivo. The interactions of UFH or ATH with the components of the fibrinolytic pathway are not well understood. Our study utilised discontinuous second order rate constant (k2 ) assays to compare the rates of inhibition of free and fibrin-associated plasmin by AT+UFH vs ATH. Additionally, we evaluated the effects of AT+UFH and ATH on plasmin generation in the presence of fibrin. The k2 values for inhibition of plasmin were 5.74 ± 0.28 x 106 M-1 min-1 and 6.39 ± 0.59 x 106 M-1 min-1 for AT+UFH and ATH, respectively. In the presence of fibrin, the k2 values decreased to 1.45 ± 0.10 x 106 M-1 min1 and 3.07 ± 0.19 x 106 M-1 min-1 for AT+UFH and ATH, respectively. Therefore, protection of plasmin by fibrin was observed for both inhibitors; however, ATH demonstrated superior inhibition of fibrin-associated plasmin. Rates of plasmin generation were also decreased by both inhibitors, with ATH causing the greatest reduction (approx. 38-fold). Nonetheless, rates of plasmin inhibition were 2–3 orders of magnitude lower than for thrombin, and in a plasma-based clot lysis assay ATH significantly inhibited clot formation but had little impact on clot lysis. Cumulatively, these data may indicate that, relative to coagulant enzymes, the fibrinolytic system is spared from inhibition by both AT+UFH and ATH, limiting reduction in fibrinolytic potential during anticoagulant therapy.

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