Synthesis and Explosion Hazards of 4-Azido-<scp>l</scp>-phenylalanine

Richardson, Mark B.; Brown, Derek B.; Vasquez, Carlos Alberto; Johnston, Kevin M.; Weiss, Gregory A.

doi:10.1021/acs.joc.8b00270

Cited by 23 publications

(15 citation statements)

References 83 publications

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“…We also incorporated an iodine atom in N -Me- d -Phe 1 to give N -methyl- p -iodo- d -phenylalanine ( N -Me- d -Phe I 1 ), to permit determination of the X-ray crystallographic phases. 15,16 Figure 1 illustrates the structure of the resulting teixobactin analogue 3 , a homologue of Lys 10 -teixobactin ( 2 ). Teixobactin analogue 3 does not form a gel and exhibits only modest activity against S. aureus (MIC=16 μg/mL).…”

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confidence: 99%

“…We postulated that N -methylation of the peptide backbone would attenuate the aggregation and permit the growth of crystals. , We discovered that N -methylation of d -Gln 4 indeed facilitated crystallization. We also incorporated an iodine atom in N -Me- d -Phe 1 to give N -methyl- p -iodo- d -phenylalanine ( N -Me- d -Phe I 1 ), to permit determination of the X-ray crystallographic phases. , Figure illustrates the structure of the resulting teixobactin analogue 3 , a homologue of Lys 10 -teixobactin ( 2 ). Teixobactin analogue 3 does not form a gel and exhibits only modest activity against S.…”

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confidence: 99%

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X-ray Crystallographic Structure of a Teixobactin Derivative Reveals Amyloid-like Assembly

et al. 2018

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This paper describes the X-ray crystallographic structure of a derivative of the antibiotic teixobactin and shows that its supramolecular assembly through the formation of antiparallel β-sheets creates binding sites for oxyanions. An active derivative of teixobactin containing lysine in place of allo-enduracididine assembles to form amyloid-like fibrils, which are observed through a thioflavin T fluorescence assay and by transmission electron microscopy. A homologue, bearing an N-methyl substituent, to attenuate fibril formation, and an iodine atom, to facilitate X-ray crystallographic phase determination, crystallizes as double helices of β-sheets that bind sulfate anions. β-Sheet dimers are key subunits of these assemblies, with the N-terminal methylammonium group of one monomer and the C-terminal macrocycle of the other monomer binding each anion. These observations suggest a working model for the mechanism of action of teixobactin, in which the antibiotic assembles and the assemblies bind lipid II and related bacterial cell wall precursors on the surface of Gram-positive bacteria.

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confidence: 99%

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confidence: 99%

X-ray Crystallographic Structure of a Teixobactin Derivative Reveals Amyloid-like Assembly

et al. 2018

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“…The cost of pAzF is considerable for large-scale production of nanobodies but it can be produced in-lab in few steps from inexpensive commercially available starting materials. In this study, pAzF was synthesized in-house following the detailed protocol reported by Gregory A. Weiss and co-workers [ 21 ]. The method is scalable to at least 50 g starting material.…”

Section: Methodsmentioning

confidence: 99%

Site-specific nanobody-oligonucleotide conjugation for super-resolution imaging

Teodori¹,

Omer²,

Märcher³

et al. 2022

JBM

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Camelid single-domain antibody fragments, also called nanobodies, constitute a class of binders that are small in size (~15 kDa) and possess antigen-binding properties similar to their antibody counterparts. Facile production of recombinant nanobodies in several microorganisms has made this class of binders attractive within the field of molecular imaging. Particularly, their use in super-resolution microscopy has improved the spatial resolution of molecular targets due to a smaller linkage error. In single-molecule localization microscopy techniques, the effective spatial resolution can be further enhanced by site-specific fluorescent labeling of nanobodies owing to a more homogeneous protein-to-fluorophore stoichiometry, reduced background staining and a known distance between dye and epitope. Here, we present a protocol for site-specific bioconjugation of DNA oligonucleotides to three distinct nanobodies expressed with an N- or C-terminal unnatural amino acid, 4-azido-L-phenylalanine (pAzF). Using copper-free click chemistry, the nanobody-oligonucleotide conjugation reactions were efficient and yielded highly pure bioconjugates. Target binding was retained in the bioconjugates, as demonstrated by bio-layer interferometry binding assays and the super-resolution microscopy technique, DNA points accumulation for imaging in nanoscale topography (PAINT). This method for site-specific protein-oligonucleotide conjugation can be further extended for applications within drug delivery and molecular targeting where site-specificity and stoichiometric control are required.

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“…Process safety scientists in the pharmaceutical industry are chemists and engineers who dedicate themselves to identify and minimize potential risks associated with thermally unstable materials, combustible dusts, and runaway reactions from R&D laboratories to manufacturing facilities. Numerous publications illustrate such work accomplished by process safety scientists. − For example, Tian et al evaluated thermal safety on a hydroamination reaction using DMSO as solvent, studied the potential autocatalytic decomposition with DMSO, and successfully launched the process for commercial production safely.…”

Section: Process Safety In the Pharmaceutical Industrymentioning

confidence: 99%

Precompetitive Collaborations in the Pharmaceutical Industry: Process Safety Groups Work Together to Reduce Hazards, from R&D Laboratories to Manufacturing Facilities

Allian

Flanagan

Mentzer

et al. 2021

ACS Chem. Health Saf.

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Process Safety scientists in the pharmaceutical industry are tasked with keeping the laboratories, manufacturing facilities, people, and environment safe from thermal runaway reactions. This group of highly trained chemists and engineers has forged an alliance stretching across company lines to help ensure the safety of the global pharmaceutical manufacturing sector. In this Commentary, we share our challenges, strategies, and opportunities for working together to ensure the safety of our respective companies and external vendors. We discuss our three platforms for collaborating and sharing ideas to help communicate the importance of pharmaceutical companies cooperating in a precompetitive space for the greater good.

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

Cited by 23 publications

References 83 publications

X-ray Crystallographic Structure of a Teixobactin Derivative Reveals Amyloid-like Assembly

X-ray Crystallographic Structure of a Teixobactin Derivative Reveals Amyloid-like Assembly

Site-specific nanobody-oligonucleotide conjugation for super-resolution imaging

Precompetitive Collaborations in the Pharmaceutical Industry: Process Safety Groups Work Together to Reduce Hazards, from R&D Laboratories to Manufacturing Facilities

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