ChemInform Abstract: Rearrangement of N<sub>α</sub>‐Protected L‐Asparagines with Iodosobenzene Diacetate. A Practical Route to β‐Amino‐L‐alanine Derivatives.

Zhang, L.; Kauffman, Goss S.; Pesti, Jaan A.; Yin, Jianhua

doi:10.1002/chin.199808177

Cited by 7 publications

(12 citation statements)

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“…Several Dapprotected variants are commercially available; herein, Dap was introduced as Boc-Dap(Cbz)-OH. In any case, Dap can be rapidly prepared following the literature 19 and protected thereafter with the appropriate group. Boc deprotection was performed with 25% trifluoroacetic acid (TFA) in dichloromethane (DCM).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

In-Peptide Synthesis of Imidazolidin-2-one Scaffolds, Equippable with Proteinogenic or Taggable/Linkable Side Chains, General Promoters of Unusual Secondary Structures

et al. 2019

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Peptidomimetics containing (S)- or (R)-imidazolidin-2-one-4-carboxylate (Imi) have been obtained by the expedient in-peptide cyclization of (S)- or (R)-α,β-diaminopropionic acid (Dap) residues. These Imi scaffolds behave as proline analogues characterized by a flat structure and a trans-restricted geometry of the preceding peptide bond and induce well-defined secondary structures in a biomimetic environment. While (S)-Imi peptides adopted a γ′-turn conformation, (R)-Imi induced the contemporary formation of a γ-turn and a rare 11-membered H-bonded structure in the 2→4 opposite direction of the sequence, identified as a ε-turn. In order to exploit these Imi scaffolds as general promoters of unusual secondary structures, proteinaceous side chains have been introduced at the N1 position of the five-membered ring, potentially mimicking any residues. Finally, the Imi rings have been equipped with unnatural side chains or with functionalized substituents, which can be utilized as linkers to chemoselectively bind the Imi-peptides onto nanoparticles, biomaterials, or diagnostic probes.

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Section: ■ Results and Discussionmentioning

confidence: 99%

In-Peptide Synthesis of Imidazolidin-2-one Scaffolds, Equippable with Proteinogenic or Taggable/Linkable Side Chains, General Promoters of Unusual Secondary Structures

et al. 2019

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“…BZI‐Ala ( 4a ) and homo‐BZI‐Ala ( 4b ), which may be considered as 3‐aza analogs of l ‐Trp and HomoTrp, respectively, were synthesized according to Scheme 2. N α ‐Cbz‐ l ‐Asn and N α ‐Cbz‐ l ‐Asn were subjected to Hoffmann rearrangement with diacetoxyiodobenzene to produce the corresponding β‐ and γ‐amines . N‐arylation was then achieved using 2‐fluoronitrobenzene in dimethylformamide, followed by reduction with Zn, formylation and cyclization in refluxing formic acid, in one pot, and subsequent acid hydrolysis of the carbobenzyloxy group.…”

Section: Resultsmentioning

confidence: 99%

“…Iodobenzene diacetate (Acros) (1.6 g, 4.88 mmol) was added to the tetrahydrofuran solution, and the reaction was stirred at room temperature for 8 h, yielding a white precipitate. The precipitate was filtered, and the precipitate was washed twice with tetrahydrofuran, yielding 0.625 g (70%) of N α ‐benzyloxycarbonyl‐β‐amino‐ l ‐alanine ( 2a ) .…”

Section: Methodsmentioning

confidence: 99%

Benzimidazole analogs of l‐tryptophan are substrates and inhibitors of tryptophan indole lyase from Escherichia coli

Harris

Phillips

2013

The FEBS Journal

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Tryptophan indole lyase (TIL), an enzyme found in Escherichia coli and related enterobacteria, produces indole from L-tryptophan (L-Trp). Indole is a signaling molecule in bacteria, affecting biofilm formation, pathogenicity and antibiotic resistance. b-(Benzimidazol-1-yl)-L-alanine (BZI-Ala), 2-amino-4-(benzimidazol-1-yl)butyric acid (homo-BZI-Ala) and 2-amino-5-(benzimidazol-1-yl)pentanoic acid (bishomo-BZI-Ala) were synthesized and tested as substrates and inhibitors of TIL. BZI-Ala is a good substrate of TIL, with K m = 300 lM, k cat = 5.6 s À1 and k cat /K m = 1.9 9 10 4 , similar to L-Trp. BZI-Ala is also a good substrate for H463F mutant TIL, which has very low activity with L-Trp. In contrast, homo-BZI-Ala was found to be a potent competitive inhibitor of TIL, with a K i of 13.4 lM. However, the higher homolog, bishomo-BZI-Ala, was inactive as an inhibitor of TIL at a concentration of 600 lM, and is thus a much weaker inhibitor. The reaction of TIL with BZI-Ala was too fast to be observed in the stopped-flow spectrophotometer, and shows an aldimine intermediate in the steady state. However, H463F TIL shows equilibrating mixtures of aldimine and quinonoid complexes in the steady state. The spectra of the reaction of TIL with homo-BZI-Ala show a rapidly formed intermediate absorbing at 340 nm, probably a gem-diamine, that decays slowly to form a quinonoid complex absorbing at 494 nm. The potent binding of homo-BZI-Ala may be due to it being a 'bi-product' analog of the indole-a-aminoacrylate complex. These results demonstrate that an amino acid substrate may be converted to a potent inhibitor of TIL simply by homologation, which may be useful in the design of other potent TIL inhibitors.

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“…The first step is a literature known Hofmann degradation. 34 Then the free amine was acetylated with 1 equiv of acetic anhydride. In the last steps the amino function was deprotected with H 2 and Pd/C, and the Fmoc group was introduced.…”

Section: Resultsmentioning

confidence: 99%

On-Bead Screening of a Combinatorial Fumaric Acid Derived Peptide Library Yields Antiplasmodial Cysteine Protease Inhibitors with Unusual Peptide Sequences

et al. 2009

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A new class of cysteine protease inhibitors based on fumaric acid derived oligopeptides was successfully identified from a high-throughput screening of a solid-phase bound combinatorial library. As target enzymes falcipain and rhodesain were used, which play important roles in the life cycles of the parasites which cause malaria (Plasmodium falciparum) and African sleeping sickness (Trypanosoma brucei rhodesiense). The best inhibitors with unusual amino acid sequences not reported before for this type of enzyme were also fully analyzed in detail in solution. K(i) values in the lower micromolar and even nanomolar region were found. Some inhibitors are even active against plasmodia and show good selectivity relative to other enzymes. Also the mechanism of action was studied and could be shown to be irreversible inhibition.

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ChemInform Abstract: Rearrangement of N_α‐Protected L‐Asparagines with Iodosobenzene Diacetate. A Practical Route to β‐Amino‐L‐alanine Derivatives.

Cited by 7 publications

References 1 publication

In-Peptide Synthesis of Imidazolidin-2-one Scaffolds, Equippable with Proteinogenic or Taggable/Linkable Side Chains, General Promoters of Unusual Secondary Structures

In-Peptide Synthesis of Imidazolidin-2-one Scaffolds, Equippable with Proteinogenic or Taggable/Linkable Side Chains, General Promoters of Unusual Secondary Structures

Benzimidazole analogs of l‐tryptophan are substrates and inhibitors of tryptophan indole lyase from Escherichia coli

On-Bead Screening of a Combinatorial Fumaric Acid Derived Peptide Library Yields Antiplasmodial Cysteine Protease Inhibitors with Unusual Peptide Sequences

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ChemInform Abstract: Rearrangement of Nα‐Protected L‐Asparagines with Iodosobenzene Diacetate. A Practical Route to β‐Amino‐L‐alanine Derivatives.

Cited by 7 publications

References 1 publication

In-Peptide Synthesis of Imidazolidin-2-one Scaffolds, Equippable with Proteinogenic or Taggable/Linkable Side Chains, General Promoters of Unusual Secondary Structures

In-Peptide Synthesis of Imidazolidin-2-one Scaffolds, Equippable with Proteinogenic or Taggable/Linkable Side Chains, General Promoters of Unusual Secondary Structures

Benzimidazole analogs of l‐tryptophan are substrates and inhibitors of tryptophan indole lyase from Escherichia coli

On-Bead Screening of a Combinatorial Fumaric Acid Derived Peptide Library Yields Antiplasmodial Cysteine Protease Inhibitors with Unusual Peptide Sequences

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ChemInform Abstract: Rearrangement of N_α‐Protected L‐Asparagines with Iodosobenzene Diacetate. A Practical Route to β‐Amino‐L‐alanine Derivatives.