Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Synthesis and Explosion Hazards of 4-Azido-l-phenylalanine.

ABSTRACT: A reliable, scalable, cost-effective, and chromatography-free synthesis of 4-azido-l-phenylalanine beginning from l-phenylalanine is described. Investigations into the safety of the synthesis reveal that the Ullman-like Cu(I)-catalyzed azidation step does not represent a significant risk. The isolated 4-azido-l-phenylalanine product, however, exhibits previously undocumented explosive characteristics.

SUBMITTER: Richardson MB

PROVIDER: S-EPMC6008159 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Synthesis and Explosion Hazards of 4-Azido-l-phenylalanine.

Richardson Mark B MB Brown Derek B DB Vasquez Carlos A CA Ziller Joseph W JW Johnston Kevin M KM Weiss Gregory A GA

The Journal of organic chemistry 20180402 8

A reliable, scalable, cost-effective, and chromatography-free synthesis of 4-azido-l-phenylalanine beginning from l-phenylalanine is described. Investigations into the safety of the synthesis reveal that the Ullman-like Cu(I)-catalyzed azidation step does not represent a significant risk. The isolated 4-azido-l-phenylalanine product, however, exhibits previously undocumented explosive characteristics. ...[more]

PMID: 29577718

Similar Datasets

α-Azido bisphosphonates: synthesis and nucleotide analogues.

Project description:The first examples of α-azido bisphosphonates [(RO)(2)P(O)](2)CXN(3) (1, R = i-Pr, X = Me; 2, R = i-Pr, X = H; 3, R = H, X = Me; 4, R = H, X = H) and corresponding β,γ-CXN(3) dGTP (5-6) and α,β-CXN(3) dATP (7-8) analogues are described. The individual diastereomers of 7 (7a/b) were obtained by HPLC separation of the dADP synthetic precursor (14a/b).

| S-EPMC3112310 | biostudies-literature

Synthesis of Azido-Globo H Analogs for Immunogenicity Evaluation.

Project description:Globo H (GH) is a tumor-associated carbohydrate antigen (TACA), and GH conjugations have been evaluated as potential cancer vaccines. However, like all carbohydrate-based vaccines, low immunogenicity is a major issue. Modifications of the TACA increase its immunogenicity, but the systemic modification on GH is challenging and the synthesis is cumbersome. In this study, we synthesized several azido-GH analogs for evaluation, using galactose oxidase to selectively oxidize C6-OH of the terminal galactose or N-acetylgalactosamine on lactose, Gb3, Gb4, and SSEA3 into C6 aldehyde, which was then transformed chemically to the azido group. The azido-derivatives were further glycosylated to azido-GH analogs by glycosyltransferases coupled with sugar nucleotide regeneration. These azido-GH analogs and native GH were conjugated to diphtheria toxoid cross-reactive material CRM197 for vaccination with C34 adjuvant in mice. Glycan array analysis of antisera indicated that the azido-GH glycoconjugate with azide at Gal-C6 of Lac (1-CRM197) elicited the highest antibody response not only to GH, SSEA3, and SSEA4, which share the common SSEA3 epitope, but also to MCF-7 cancer cells, which express these Globo-series glycans.

| S-EPMC8796297 | biostudies-literature

Resolving phenylalanine metabolism sheds light on natural synthesis of benzylpenicillin in Penicillium chrysogenum

Project description:Industrial production of penicillin G by Penicillium chrysogenum requires medium supplementation with the side chain precursor phenylacetate. However, P.chrysogenum grown in presence of phenylalanine as sole nitrogen source formed detectable extracellular amounts of phenylacetate and penicillin G. To get more insights in the metabolism implicated, chemostat-cultivation in presence of 13C9-phenylalanine were carried out. Quantification and modeling of the labeled metabolite pools indicated that phenylalanine was i) incorporated in nascent protein, ii) transaminated to phenylpyruvate and further converted by oxidation or by decarboxylation and iii) oxidized into tyrosine and subsequently assimilated in the homogentisate pathway. Comparative transcriptome analysis of phenylalanine and (NH4)2SO4 grown P.chrysogenum cultures enabled to identify two putative 2-oxo acid decarboxylases Pc13g9300 and Pc18g01490. Both cDNAs were cloned and expressed in the decarboxylase-free Saccharomyces cerevisiae CEN.PK711-7C (pdc1delta, 5delta, 6delta, aro10delta, thi3delta) strain that has lost the ability to grow on glucose as sole carbon source or on phenylalanine as sole nitrogen source. Only Pc13g09300 was able to restore growth on glucose and on phenylalanine, demonstrating that this gene encodes a dual substrate pyruvate, phenylpyruvate decarboxylase. This newly identified thiamine-dependent 2-oxo acid decarboxylase provides clues to explain the formation of phenylacetate via an Ehrlich-like pathway in P.chrysogenum.

2011-11-05 | GSE32097 | GEO

Conformation-specific detection of calmodulin binding using the unnatural amino acid p-azido-phenylalanine (AzF) as an IR-sensor.

Project description:Calmodulin (CaM) is a very conserved, ubiquitous, eukaryotic protein that binds four Ca2+ ions with high affinity. It acts as a calcium sensor by translating Ca2+ signals into cellular processes such as metabolism, inflammation, immune response, memory, and muscle contraction. Calcium binding to CaM leads to conformational changes that enable Ca2+/CaM to recognize and bind various target proteins with high affinity. The binding mode and binding partners of CaM are very diverse, and a consensus binding sequence is lacking. Here, we describe an elegant system that allows conformation-specific detection of CaM-binding to its binding partners. We incorporate the unnatural amino acid p-azido-phenylalanine (AzF) in different positions of CaM and follow its unique spectral signature by infrared (IR)-spectroscopy of the azido stretching vibration. Our results suggest that the AzF vibrational probe is sensitive to the chemical environment in different CaM/CaM-binding domain (CaMBD) complexes, which allows differentiating between different binding motifs according to the spectral characteristics of the azido stretching mode. We corroborate our results with a crystal structure of AzF-labelled CaM (CaM108AzF) in complex with a binding peptide from calmodulin-dependent protein kinase II? identifying the structural basis for the observed IR frequency shifts.

| S-EPMC6224318 | biostudies-literature

Synthesis of an azido-tagged low affinity ratiometric calcium sensor.

Project description:Changes in high localised concentrations of Ca2+ ions are fundamental to cell signalling. The synthesis of a dual excitation, ratiometric calcium ion sensor with a Kd of 90 ?M, is described. It is tagged with an azido group for bioconjugation, and absorbs in the blue/green and emits in the red region of the visible spectrum with a large Stokes shift. The binding modulating nitro group is introduced to the BAPTA core prior to construction of a benzofuran-2-yl carboxaldehyde by an allylation-oxidation-cyclisation sequence, which is followed by condensation with an azido-tagged thiohydantoin. The thiohydantoin unit has to be protected with an acetoxymethyl (AM) caging group to allow CuAAC click reaction and incorporation of the KDEL peptide endoplasmic reticulum (ER) retention sequence.

| S-EPMC4660056 | biostudies-literature

Synthesis and Protein Incorporation of Azido-Modified Unnatural Amino Acids.

Project description:Two new azidophenylalanine residues (3 and 4) have been synthesized and, in combination with 4-azido-L-phenylalanine (1) and 4-azidomethyl-L-phenylalanine (2), form a series of unnatural amino acids (UAAs) containing the azide vibrational reporter at varying distances from the aromatic ring of phenylalanine. These UAAs were designed to probe protein hydration with high spatial resolution by utilizing the large extinction coefficient and environmental sensitivity of the azide asymmetric stretch vibration. The sensitivity of the azide reporters was investigated in solvents that mimic distinct local protein environments. Three of the four azido-modified phenylalanine residues were successfully genetically incorporated into a surface site in superfolder green fluorescent protein (sfGFP) utilizing an engineered, orthogonal aminoacyl-tRNA synthetase in response to an amber codon with high efficiency and fidelity. SDS-PAGE and ESI-Q-TOF mass analysis verified the site-specific incorporation of these UAAs. The observed azide asymmetric stretch in the linear IR spectra of these UAAs incorporated into sfGFP indicated that the azide groups were hydrated in the protein.

| S-EPMC4603873 | biostudies-literature

Synthesis of d- and l-Phenylalanine Derivatives by Phenylalanine Ammonia Lyases: A Multienzymatic Cascade Process.

Project description:The synthesis of substituted d-phenylalanines in high yield and excellent optical purity, starting from inexpensive cinnamic acids, has been achieved with a novel one-pot approach by coupling phenylalanine ammonia lyase (PAL) amination with a chemoenzymatic deracemization (based on stereoselective oxidation and nonselective reduction). A simple high-throughput solid-phase screening method has also been developed to identify PALs with higher rates of formation of non-natural d-phenylalanines. The best variants were exploited in the chemoenzymatic cascade, thus increasing the yield and ee?value of the d-configured product. Furthermore, the system was extended to the preparation of those l-phenylalanines which are obtained with a low ee?value using PAL amination.

| S-EPMC4955227 | biostudies-literature

Synthesis of D- and L-phenylalanine derivatives by phenylalanine ammonia lyases: a multienzymatic cascade process.

Project description:The synthesis of substituted D-phenylalanines in high yield and excellent optical purity, starting from inexpensive cinnamic acids, has been achieved with a novel one-pot approach by coupling phenylalanine ammonia lyase (PAL) amination with a chemoenzymatic deracemization (based on stereoselective oxidation and nonselective reduction). A simple high-throughput solid-phase screening method has also been developed to identify PALs with higher rates of formation of non-natural D-phenylalanines. The best variants were exploited in the chemoenzymatic cascade, thus increasing the yield and ee value of the D-configured product. Furthermore, the system was extended to the preparation of those L-phenylalanines which are obtained with a low ee value using PAL amination.

| S-EPMC4531825 | biostudies-literature

Solid-phase synthesis of DNA-encoded libraries via an "aldehyde explosion" strategy.

Project description:We report chemistry suitable for the solid-phase synthesis of DNA-encoded libraries with an unusually high level of structural diversity. The strategy involves "exploding" an immobilized aldehyde into a plethora of different functional groups under DNA-compatible conditions.

| S-EPMC7298663 | biostudies-literature

Resolving phenylalanine metabolism sheds light on natural synthesis of benzylpenicillin in Penicillium chrysogenum

2011-11-05 | E-GEOD-32097 | biostudies-arrayexpress