Synthesis of O-acylbenzohydroxamic acids and their use in peptide synthesis

Govindachari, T. R.; Nagarajan, K.; Rajappa, S.; Akerkar, A. S.; Iyer, Vivekanantan S.

doi:10.1016/s0040-4020(01)92524-4

Cited by 18 publications

(4 citation statements)

References 11 publications

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“…mp 108-1 10 OC (Gorindachari et al, 1966)); TLC Rf 0.94 (97:3, CHC13:MeOH) single spot visualized with 1, vapor, ninhydrin negative. N-Acetoxysuccinimide.…”

Section: Methodsmentioning

confidence: 99%

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The role of methionine-192 of the chymotrypsin active site in the binding and catalysis of mono(amino acid) and peptide substrates

Treadway¹,

Schultz²

1976

Biochemistry

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We find that specific oxidation for the Met-192 residue in delta-chymotrypsin to methionine sulfoxide results in a twofold increase in Km(app) and unchanged kcat in the hydrolysis of N-acetyl mono(amino acid) amide substrates. However, the catalyzed hydrolyses of N-acetyl dipeptide amide substrates by (methionine sulfoxide)-192-delta-chymotrypsin (MS-delta-Cht) shows a four- to fivefold decrease in kcat and unchanged Km(app) with respect to delta-chymotrypsin. Hydrolysis of alpha-casein by MS-delta-Cht shows a similar 4.2-fold decrease in kcat. These results imply that the Met-192 acts differently with substrates that bind only in the primary, S1, binding site (i.e., AcPheNH2) from those that bind to more extended regions of the enzyme active site. In the binding of c+AcPheNH2 and AcTrpNH2, the results support a mechanism in which the Met-192 acts to slow the rate of sustrate dissociation from the Michaelis complex to free substrate and enzyme. This is in agreement with the x-ray crystallographic structure of dioxane inhibited alpha-chymotrypsin (Steitz, T., et al. (1969), J. Mol. Biol. 46, 337). However, this mechanism is not apparent when peptide and protein substrates bind. The decrease in kcat on Met-192 modification of approximately fivefold in the hydrolysis of polypeptide substrates show a small, but significant, catalytic contribution of the Met-192 toward the lowering of the energy of activation polypeptide substrate hydrolysis by chymotrypsin. This may support the crystallographic model of Fersht et al. (Fersht, A., et al. (1973), Biochemistry 12, 2035) in which it is proposed that the Met-192 participates in the distortion of bound polypeptide substrates toward the reaction transition-state configuration and, thus, plays a role in catalysis. However, if this mechanism occurs, the effect is small, only contributing about 1 kcal/mol to the lowering of the reaction activation energy.

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“…mp 108-1 10 OC (Gorindachari et al, 1966)); TLC Rf 0.94 (97:3, CHC13:MeOH) single spot visualized with 1, vapor, ninhydrin negative. N-Acetoxysuccinimide.…”

Section: Methodsmentioning

confidence: 99%

“…Cbz-Phe-Gly-OEt was prepared by identical procedures as above starting with 20 g of Cbz-L-Phe and 9.4 g of HCl-Gly-OEt: yield of 18.9 g (67% yield); mp 107.0-108.0 °C (lit. mp 108-110 °C (Gorindachari et al, 1966)); TLC 0.94 (97:3, CHCl3:MeOH) single spot visualized with L vapor, ninhydrin negative.…”

Section: Methodsmentioning

confidence: 99%

The role of methionine-192 of the chymotrypsin active site in the binding and catalysis of mono(amino acid) and peptide substrates

Treadway¹,

Schultz²

1976

Biochemistry

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“…Subsequently, various nitrile oxide derivatives were evaluated for peptide synthesis. 181 Among these, N -trimethylacetyl-hydroxylamine proved to be the optimal choice for preparing active esters of proteinogenic amino acids (Scheme 38). 182 This method was applied for the synthesis of di- and tripeptides but was not amenable for larger peptides due to the competing Lossen rearrangement reaction, which gave isocyanate by-product.…”

Section: Active Esters Formed Upon Reaction With Activating Reagentsmentioning

confidence: 99%

Active ester-based peptide bond formation and its application in peptide synthesis

2023

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“…A study on the synthesis of benzohydroxamic acid esters and the corresponding nitriles 22 via the mechanism Ar-CsN-0 + RCOOH -* RCO-O-NH-CO-Ar is of interest. The yield of esters in this reaction varies from 65 to 100%.…”

Section: Activated A-acylaminoacid Estersmentioning

confidence: 99%