62234-40-6Relevant articles and documents
COMPOSITIONS AND METHODS FOR THE TREATMENT OF BACTERIAL INFECTIONS
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Page/Page column 168; 169, (2018/02/28)
Compositions and methods for the treatment of bacterial infections include compounds containing dimers of cyclic heptapeptides. In particular, compounds can be used in the treatment of bacterial infections caused by Gram-negative bacteria.
Benzimidazole analogs of l-tryptophan are substrates and inhibitors of tryptophan indole lyase from Escherichia coli
Harris, Austin P.,Phillips, Robert S.
, p. 1807 - 1817 (2013/06/05)
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. β-(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 Km = 300 μm, kcat = 5.6 s-1 and kcat/Km = 1.9 × 104, 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 Ki of 13.4 μm. However, the higher homolog, bishomo-BZI-Ala, was inactive as an inhibitor of TIL at a concentration of 600 μm, 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-α-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. β-(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 tryptophan indole-lyase (TIL), an enzyme found in Escherichia coli and related enterobacteria. BZI-Ala is a good substrate of TIL, homo-BZI-Ala is a potent competitive inhibitor of TIL, with Ki of 13.4 μM, but bishomo-BZI-Ala, was inactive as an inhibitor of TIL. 2013 The Authors Journal compilation
An Improved Preparation of N2-tert-Butoxycarbonyl- and N 2-Benzyloxycarbonyl-(S)-2,4-diaminobutanoic Acids
Andruszkiewicz, Ryszard,Rozkiewicz, Dorota
, p. 1049 - 1056 (2007/10/03)
Utilizing N-benzyloxycarbonyl- (1a) and N-tert-butoxycarbonyl-(S) -glutamine (1b), a highly efficient and practical method for the synthesis of N2-benzyloxycarbonyl- and N 2-tert-butoxycarbonyl-(S)-2,4-diamino-butanoic acids (2a and 2b) has been developed. Reaction of (S)-glutamine derivatives with iodosobenzene diacetate in a mixture of THF-water at 4°C afforded selectively protected (S)-2,4-diaminobutanoic acids in good yields.
