Direct monitoring of biocatalytic deacetylation of amino acid substrates by <sup>1</sup>H NMR reveals fine details of substrate specificity

Cesare, Silvia De; McKenna, Catherine A; Mulholland, Nicholas P.; Murray, Lorna; Bella, Juraj; Campopiano, Dominic J.

doi:10.1039/d1ob00122a

Cited by 2 publications

(4 citation statements)

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“…For the synthesis of compound 9 , Ala−OMe ⋅ HCl was initially converted into Ac−Ala−OMe by using AcCl in DCM. The obtained compound was then hydrolyzed at the ester functionality to 9 in basic conditions and used in the next steps [26] . Amine 6 was used as the starting point for the coupling reaction with different amino acids to obtain compounds 7 a – c , e – g , i , k , l – n .…”

Section: Resultsmentioning

confidence: 99%

“…Acetyl‐L‐alanine ( 8 ) . According with published procedure compound 8 was obtained as a colorless oil [26] …”

Section: Methodsmentioning

confidence: 99%

“…The obtained compound was then hydrolyzed at the ester functionality to 9 in basic conditions and used in the next steps. [26] Amine 6 was used as the starting point for the coupling reaction with different amino acids to obtain compounds 7 a-c,e-g,i,k,l-n. The subsequent N-deprotection fur-…”

Section: Design and Synthesis Of Compoundsmentioning

confidence: 99%

“…According with published procedure compound 8 was obtained as a colorless oil. [26] General procedure i) To a solution of the corresponding carboxylic acid (1 eq, 0.04 mmol) in dry DCM (5 mL) at 0 °C, EDCI (1.2 eq, 0.048 mmol), HOBt (1.5 eq, 0.06 mmol) and DIPEA (4 eq, 0.16 mmol) were added. After 10 min, the corresponding amine (1.2 eq, 0.048) was added.…”

Section: General Chemical Informationmentioning

confidence: 99%

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Design and Synthesis of Oligopeptidic Parvulin Inhibitors

et al. 2022

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Pin1 catalyzes the cis‐trans isomerization of pThr‐Pro or pSer‐Pro amide bonds of various proteins involved in several physio/pathological processes. In this framework, recent research activity is directed toward the identification of new selective Pin1 inhibitors. Here, we developed a set of peptide‐based Pin1 inhibitors. Direct‐binding experiments allowed the identification of the peptide‐based inhibitor 5 k (methylacetyl‐l‐alanyl‐l‐histidyl‐l‐prolyl‐l‐phenylalaninate) as a potent ligand of Pin1. Notably, 5 k binds Pin1 with higher affinity than Pin4. The comparative analysis of molecular models of Pin1 and Pin4 with the selected compound gave a rational explanation of the biochemical activity and pinpointed the chemical elements that, if opportunely modified, may further improve inhibitory potency, pharmacological properties, and selectivity of future peptide‐based parvulin inhibitors. Since 5 k showed limited cell penetration and no antiproliferative activity, it was conjugated to a polyarginine stretch (R8), known to promote cell penetration of peptides, to obtain the R8–5 k derivative, which displayed antiproliferative effects on cancer cell lines over non‐tumor cells. The effect of R8 on cell proliferation was also investigated. This work warrants caution about applying the R8 strategy in the development of cell‐penetrating antiproliferative peptides, as it is not inert.

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Section: Resultsmentioning

confidence: 99%

“…Acetyl‐L‐alanine ( 8 ) . According with published procedure compound 8 was obtained as a colorless oil [26] …”

Section: Methodsmentioning

confidence: 99%

Section: Design and Synthesis Of Compoundsmentioning

confidence: 99%

Section: General Chemical Informationmentioning

confidence: 99%

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Design and Synthesis of Oligopeptidic Parvulin Inhibitors

et al. 2022

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First Insight into the Degradome of Aspergillus ochraceus: Novel Secreted Peptidases and Their Inhibitors

Shestakova,

Fatkulin,

Surkova

et al. 2024

IJMS

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Aspergillus fungi constitute a pivotal element within ecosystems, serving as both contributors of biologically active compounds and harboring the potential to cause various diseases across living organisms. The organism’s proteolytic enzyme complex, termed the degradome, acts as an intermediary in its dynamic interaction with the surrounding environment. Using techniques such as genome and transcriptome sequencing, alongside protein prediction methodologies, we identified putative extracellular peptidases within Aspergillus ochraceus VKM-F4104D. Following manual annotation procedures, a total of 11 aspartic, 2 cysteine, 2 glutamic, 21 serine, 1 threonine, and 21 metallopeptidases were attributed to the extracellular degradome of A. ochraceus VKM-F4104D. Among them are enzymes with promising applications in biotechnology, potential targets and agents for antifungal therapy, and microbial antagonism factors. Thus, additional functionalities of the extracellular degradome, extending beyond mere protein substrate digestion for nutritional purposes, were demonstrated.

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Direct monitoring of biocatalytic deacetylation of amino acid substrates by ¹H NMR reveals fine details of substrate specificity

Abstract: Amino acids are key synthetic building blocks that can be prepared in an entiopure form by biocatalytic methods. We show that the L-selective ornithine deacetylase ArgE catalyses hydrolysis of a...

Cited by 2 publications

References 52 publications

Design and Synthesis of Oligopeptidic Parvulin Inhibitors

Design and Synthesis of Oligopeptidic Parvulin Inhibitors

First Insight into the Degradome of Aspergillus ochraceus: Novel Secreted Peptidases and Their Inhibitors

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Direct monitoring of biocatalytic deacetylation of amino acid substrates by 1H NMR reveals fine details of substrate specificity

Abstract: Amino acids are key synthetic building blocks that can be prepared in an entiopure form by biocatalytic methods. We show that the L-selective ornithine deacetylase ArgE catalyses hydrolysis of a...

Cited by 2 publications

References 52 publications

Design and Synthesis of Oligopeptidic Parvulin Inhibitors

Design and Synthesis of Oligopeptidic Parvulin Inhibitors

First Insight into the Degradome of Aspergillus ochraceus: Novel Secreted Peptidases and Their Inhibitors

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Direct monitoring of biocatalytic deacetylation of amino acid substrates by ¹H NMR reveals fine details of substrate specificity