Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 27 for “"Lanthionine"”.
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Synthesis and Biological Studies of Lanthionine Derivatives
… of PG. During this work, we synthesized meso-lanthionine, the monosulfur analogue of meso A2pm, and some of its derivatives. As these compounds are susceptible to enter PG biosynthesis via MurE enzymatic addition onto UDP (S) Ala γ (R) Glu, their use in a new labeling method has been …
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Mechanistic Studies of Lantibiotic Biosynthetic Enzymes and Discovery of Novel Lanthionine-Containing Peptides
… peptides containing unique thioether crosslinks, lanthionines and methyllanthionines. These motifs are introduced posttranslationally in a two-step process, which involves the dehydration of serines and threonines into dehydroalanines and dehydrobutyrines, respectively, and subsequent …
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Computational modeling-based discovery of novel classes of anti-inflammatory drugs that target lanthionine synthetase C-like protein 2
Lanthionine synthetase C-like protein 2 (LANCL2) is a member of the LANCL protein family, which is broadly expressed throughout the body. LANCL2 is the molecular target of abscisic acid (ABA), a compound with insulin-sensitizing and immune modulatory actions. LANCL2 is required for membrane binding …
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From Peptide Precursors to Lanthionine -Containing Peptide Antibiotics Using the First Isolated and Active Lacticin 481 Synthetase: Mechanistic Studies and Peptide Engineering
The putative dehydratase SpaB involved in the biosynthesis of subtilin was heterologously overexpressed in E. coli and purified by metal-chelated affinity chromatography. However, in vitro reconstitution using the purified SpaB, SpaC, and the substrate SpaS was unsuccessful. As a result, the …
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Mechanistic studies of lanthipeptide biosynthesis
… incorporated thioether crosslinks named lanthionine. This family of natural products has garnered substantial attention during the past few decades due to their favorable biological activities and the potential for engineering. This thesis focuses on a subclass of lanthipeptides, the …
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Investigations into the roles and molecular mechanisms of LanC-like proteins
… by the characteristic thioether crosslinks lanthionine and methyllanthionine. Among the various biological activities that lanthipeptides exhibit, the anti-microbial activities shown by many members of the family (hence named lantibiotics) have drawn the most attention and make them …
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Structural investigation of lanthipeptides involved in substrate controlled pathways and methods for leader peptide removal
… the structural characterization and mechanism of lanthionine synthetases is fully understood. However, a difficult obstacle for high throughput studies of these natural products is removal of the leader peptide. Chapter 2 discusses the development of a general method using unnatural amino acid …
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Evaluation of methodology for determination of availability of amino acids and energy in feedstuffs for poultry
… vitro assays included pepsin digestibility and lanthionine analysis. In vivo methods involved protein quality chick assay, AA bioavailability chick assay, and true AA digestibility and TMEn assay using conventional and cecectomized cockerels. Cecal retention of AA and effect of hindgut microbes …
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Total Synthesis of Naturally Occurring Antimicrobial Peptides
… by four intramolecular thioether linked (methyl)lanthionine bridges. It was isolated from the New Zealand extremophilic microorganism Thermogemmatispora strain T81, collected at Tikitere (Hell’s Gate), Rotorua. However, the chemical and biological properties of tikitericin haven’t been …
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New chemical and biosynthetic methodologies for the study of lanthipeptides
… One of the largest classes of RiPPs is the lanthionine-containing peptides (lanthipeptides), which are characterized by intramolecular thioether crosslinks dubbed lanthionine (Lan) and methyllanthionine (MeLan). The evolvability and brevity of lanthipeptide biosynthetic pathways as well as …
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Structural and Biochemical Studies of Nisin *Biosynthesis and Autoimmunity
… structural basis of how the characteristic nisin lanthionine rings are installed by the enzyme NisC and (2) how Lactococcus lactis spp., despite producing an effective bacteriocin like nisin, is resistant to the toxic effects of nisin. The results described here together provide the first …
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Investigations of the Substrate Specificity of Lacticin 481 Synthetase and Utilization in Peptide Engineering Applications
… introduce dehydrated, phosphorylated, and lanthionine cross-linked amino acids into therapeutically relevant non-lantibiotic peptides. Furthermore, enzymatically installed dehydro amino acids were used as sites of ligation with a variety of thiol nucleophiles for the preparation of peptide …
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Investigating the Mechanisms of the Biosynthesis of Lexapeptide
… are characterised by the presence of lanthionine macrocycles and α,β-unsaturated amino acids such as 2,3-dehydroalanine (Dha) and (Z)-2,3-dehydrobutyrine (Dhb). Currently, the only lanthipeptide that has been approved by the Food and Drugs Administration (FDA) is Nisin which has been …
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Exploring and understanding lantibiotic biosynthesis
… lanthipeptides are thioether crosslinks, called lanthionine and methyl lanthionine. The crosslinks are formed via the dehydration of serine and threonine residues to dehydroalanine (Dha) and dehydrobutyrine (Dhb) residues, respectively, followed by Michael-type addition of cysteines to the …
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Investigation and application of substrate tolerant thioether forming enzymes
… dehydro amino acids to afford the small molecule lanthionine in mammalian systems. To test this hypothesis, in chapter 3, I developed two LC/MS/MS methods to quantify endogenous lanthionine concentrations in both wild type and LanCL knockout mouse brains, where LanCL proteins are highly expressed. …
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Bioengineering of nisin to enhance functionality against dairy pathogens
… a specific bacteriocin group, the lantibiotics (Lanthionine-containing antibiotics). Their numerous methods of appliance in a food setting and how their gene-encoded nature can be modified to improve on overall bioactivity and functionality are explored here. The use of a lantibiotic (lacticin …
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Mechanistic and synthetic studies on the prochlorosin and cytolysin families of lanthipeptides
… contain the characteristic thioether residues lanthionine (Lan) and methyllanthionine (MeLan). Installation of thioether crosslinks in lanthipeptide biosynthesis is carried out by designated synthetases and involves dehydration of Ser/Thr residues and cyclization via Michael-type addition. The …
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Chemical and chemoenzymatic syntheses of lantibiotics and other bioactive cyclic peptides
… presence of the thioether-containing crosslinks lanthionine and methyllanthionine and includes many members with promising activities against clinically-relevant bacterial pathogens, including drug-resistant strains. These peptides are biosynthesized by translation of a linear precursor peptide …
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The biosynthesis and discovery of lanthipeptides
… are polypeptides enzymatically decorated with lanthionine rings and sometimes other post-translational modifications, which dramatically elevate their protease-resistances, improved their chemical stabilities, and increased their structural complexity. To add onto the structure knowledge and …
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Diverse functions of LanC-like proteins in mammalian cells
… by LanCL2 involves formation of DL-(methyl)lanthionine linkages. In order to probe the biological function of C-glutathionylation in mammalian cells, affinity purification mass spectrometry-based (AP-MS) proteomic analysis was performed which is presented in Chapter 3. Based on the …
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