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.
Results
Showing 1 to 20 of 21 for “"Dehydroalanine"”.
-
Convergent Site-Selective Carbohydrate-Peptide Ligations With Dehydroalanine and Aziridine -2 -Carboxylic Acid-Containing Peptides
… was realized through the incorporation of dehydroalanine and aziridine-2-carboxylic acid residues into peptides and subsequent conjugation of the resulting peptide electrophiles with various thiols. Oligosaccharides incorporating a suitable anomeric thio-functionality were prepared via …
-
Chemical and Enzymatic Synthesis of Dehydropeptides and Their Fluoro Analogs
Fluorine-substituted dehydroalanine can lead to irreversible linkages of nucleophile to dehydroalanines by an addition elimination mechanism and can be applied to the design of enzyme inhibitors and active site affinity labels. Fluorodehydroalanine has been synthesized from serine in 7 steps with a …
-
Development of Protein Degraders Inspired by Chemical Modifications
… of the chemical modification-inspired dehydroalanine (Dha)-based protein degraders, including their synthesis, optimization, mechanistic elucidation, and transferability assessment. First, a Dha-based bromodomain-containing protein 4 (BRD4) degrader was synthesized and demonstrated to …
-
Investigations into the biosynthesis and mode of action of the phosphonate antibiotic dehydrophos
… of dehydrophos, a phosphonate analogue of dehydroalanine, undergoes a tautomeric rearrangement followed by hydrolysis to yield methyl acetylphosphonate, a structural analogue of pyruvate, and known inhibitor of pyruvate dehydrogenase and pyruvate oxidase. To identify genes necessary for the …
-
Investigation of phosphonate biosynthesis: I. Structure of dehydrophos II. Mechanism of hydroxyethylphosphonate dioxygenase
… containing an aminophosphonate analogue of dehydroalanine. This structure was confirmed through organic synthesis. Hydroxyethylphosphonate dioxygenase (HEPD) catalyzes a biochemically unprecedented carbon-carbon bond cleavage reaction as part of the early steps of phosphinothricin …
-
SORTASE AND CHEMICAL BIOLOGY AS TOOLS TO STUDY UBIQUITINATION
… ubiquitination system in combination with dehydroalanine chemistry to begin developing context-specific deubiquitinating enzyme (DUB) probes. We demonstrate early prospects of this strategy to capture DUB enzymes such as USP2 and highlight some key optimization points for future development …
-
Mechanistic Investigations of Cyclase Enzymes Involved in Lantibiotic Biosynthesis
… toward intramolecular Michael addition to the dehydroalanine and dehydrobutyrine residues in the peptide. Sequence alignments of both the LanC and LanM families of enzymes reveal four conserved residues, two cysteines and two histidines. Mutants of SpaC replacing the conserved cysteines with …
-
Biosynthesis of the antimicrobial peptide epilancin 15X
… and hydrolysis of the resulting N-terminal dehydroalanine residue. A pyruvyl group thus formed is finally reduced to Lac by a dehydrogenase (ElxO). Using substrate analogs synthesized by solid-phase peptide synthesis or heterologously expressed in Escherichia coli, the enzymatic activities …
-
Fragment synthesis: pharmacophore and diversity oriented approaches
… amino and acidic residues a campaign with dehydroalanine was under taken. This would allow for the installation of the second ring by pericyclic chemistry as well as using chemistry previously established. This pericyclic chemistry was also applied to synthesising spirocycles from rings …
-
Chemical Mutagenesis for the Modulation and Study of Protein Function and Dysfunction within Alzheimer’s Disease
… the synthetically versatile non-canonical AA dehydroalanine (Dha), we explore diverse sidechains at key residues along the binding loop of the SdAb and identify a non-canonical sidechain that potently enhances the inhibition of Ab’s primary nucleation. The second application focuses on the …
-
Investigating the Mechanisms of the Biosynthesis of Lexapeptide
… 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 used as a food preservative for over 40 years. This research focuses …
-
Investigations into the roles and molecular mechanisms of LanC-like proteins
… a Michael-type addition of a cysteinyl thiol to dehydroalanine and dehydrobutyrine, catalyzed by the prokaryotic lantibiotic cyclase (LanC) or the cyclase domain in a multi-functional lantibiotic synthetase. Intriguingly, despite the lack of evidence of the presence of lanthipeptides in …
-
Organometallic Palladium Reagents for Polypeptide Bioconjugation and Macrocyclization
… to linearize the macrocycle and form a dehydroalanine adduct for further modification. This approach is used to successfully linearize stapled peptides and aryl/alkyl-linked bicyclic peptides. Furthermore, the protocol maintained sequencing integrity even with as little as 50 pg of …
-
Adiciones 1,4-conjugadas a deshidroalaninas quirales para la síntesis de aminoácidos no naturales
… Previously, the reactivity of a chiral cyclic dehydroalanine against sulfur nucleophiles (S-nucleophiles) has been studied, allowing the access to cysteine derivatives of high biological interest. Therefore, based on this works, in this Thesis we intend to expand this methodology to different …
-
Biomedical applications for bacteriocins in infection and oncology
… presence of unusual amino acid residues such as dehydroalanine (Dha), dehydrobutyrine (Dhb) and lanthionine/ methyllanthionine. Interest in using bacteriocins as alternative therapeutics in multiple settings has grown in recent years. Nisin in particular has been the subject of many studies due …
-
DNA catalysts as phosphatases and as phosphoserine lyases
… the context of peptide sequence discrimination. Dehydroalanine (Dha) is a non-proteinogenic electrophilic amino acid that serves as a synthetic intermediate or product in the biosynthesis of several bioactive cyclic peptides such as lantibiotics, thiopeptides and microcystins. DNA enzymes were …
-
Biosynthesis and engineering of lanthipeptide natural products for novel applications
… that carries out the asymmetric reduction of dehydroalanine to D-alanine. The enzyme displays great substrate tolerance allowing incorporation of D-alanines into a range of non-native substrates. As ribosomally synthesized peptides are generally limited to L-amino acid building blocks, methods …
-
STRUCTURAL AND BIOCHEMICAL CHARACTERIZATION OF THE BACTERIAL FLAGELLAR MOTOR HOOK COMPLEX AND THE MS:C-RING INTERFACE
… formation pathway, including wild type (WT), the dehydroalanine (DHA) intermediate and the LA cross-linked FlgE heterodimer. The structural studies were augmented with site-directed mutagenesis experiments to probe the FlgE active site, revealing the extensive role that the hydrogen bonding …
-
The Gas-Phase Oxidation of Cationic Bioanalytes via Ion/Ion Reactions
Several solution-phase derivatizations have recently been implemented in the gas-phase through the interaction between oppositely charged ions, viz., ion/ion reactions. The work presented here primarily focuses on the oxidation of bioanalytes via ion/ion reactions with periodate and persulfate …
-
Exploring and understanding lantibiotic biosynthesis
… dehydration of serine and threonine residues to dehydroalanine (Dha) and dehydrobutyrine (Dhb) residues, respectively, followed by Michael-type addition of cysteines to the dehydrated residues. Nisin, a class I lantibiotic produced by Lactococcus lactis, is one of the oldest known antibiotics. In …
Page 1 of 2