2768-53-8

Usage

Chemical Properties

White powder

Uses

Substrate for carboxypeptidase Y.

InChI:InChI=1/C20H22N2O5/c1-14(21-20(26)27-13-16-10-6-3-7-11-16)18(23)22-17(19(24)25)12-15-8-4-2-5-9-15/h2-11,14,17H,12-13H2,1H3,(H,21,26)(H,22,23)(H,24,25)/t14-,17-/m0/s1

Upstream product

• 2953-41-5 (S)-ethyl 2-((S)-2-(((benzyloxy)carbonyl)amino)propanamido)-3-phenylpropanoate 
• 1142-20-7 N-Cbz-Ala 
• 108-12-3 isopentanoyl chloride 
• 95617-89-3 Z-(S)-Ala-(S)-Phe-NH₂ 
• 3235-14-1 (S)-2-((S)-2-Benzyloxycarbonylamino-propionylamino)-3-phenyl-propionic acid methyl ester 
• 63-91-2 L-phenylalanine 
• 6233-97-2 Z-Ala-OPcp 
• 2688-06-4 Z-L-Ala-O-N=C(CH₃)-C₆H₄-m-NO₂ 
• 2543-29-5 Cbz-L-ala-L-phe-Cbz 
• 478170-85-3 C₂₂H₂₀N₄O₄ 
• 6695-43-8 (S)-tert-butyl 2-((S)-2-(((benzyloxy)carbonyl)amino)propanamido)-3-phenylpropanoate 
• 203640-41-9 Z-L-Ala 2,2,2-trifluoroethyl ester 
• 18979-06-1 H-Ala-Phe-NH₂ 
• 501-53-1 benzyl chloroformate 

Downstream Products

• 176040-41-8 Z-Ala-(D,L)-Phe-OMe 
• 20911-65-3 N-Cbz-L-alanyl-L-phenylalanine succinimido ester 
• 883725-92-6 ZAFA-t-Bu ester 
• 76146-33-3 Z--Ala--Phe--Val-OMe 
• 76146-32-2 Z--Ala--Phe--Val-OMe 
• 65118-56-1 Cbz-Ala-Phe-Leu-NH₂ 
• 92278-79-0 Z-Ala-Phe-OBzl-SO₃Na 
• 123484-65-1 [(S)-1-((S)-4-Benzyl-5-oxo-4,5-dihydro-oxazol-2-yl)-ethyl]-carbamic acid benzyl ester 
• 3235-14-1 (S)-2-((S)-2-Benzyloxycarbonylamino-propionylamino)-3-phenyl-propionic acid methyl ester 
• 6695-43-8 (S)-tert-butyl 2-((S)-2-(((benzyloxy)carbonyl)amino)propanamido)-3-phenylpropanoate 
• 179675-16-2 {(S)-5-[(S)-2-((S)-2-Benzyloxycarbonylamino-propionylamino)-3-phenyl-propionylamino]-6-oxo-heptyl}-carbamic acid benzyl ester 
• 179913-08-7 {(R)-5-[(S)-2-((S)-2-Benzyloxycarbonylamino-propionylamino)-3-phenyl-propionylamino]-6-oxo-heptyl}-carbamic acid benzyl ester 
• 130839-27-9 (N-Benzyloxycarbonyl-L-alanyl-L-phenylalanyl)diazomethane 
• 1027546-01-5 (E)-(S)-4-[(S)-2-((S)-2-Benzyloxycarbonylamino-propionylamino)-3-phenyl-propionylamino]-6-(trityl-carbamoyl)-hex-2-enoic acid ethyl ester 

Relevant academic research and scientific papers

Performance improvement of araujiain, a cystein phytoprotease, by immobilization within calcium alginate beads

The effect of immobilization within alginate beads on the performance of araujiain in aqueous and non-aqueous media was studied. Optimum pH and temperature, thermal and pH-stability, kinetic parameters and operational stability were determined. Entrapped

A new class of α-ketoamide derivatives with potent anticancer and anti-SARS-CoV-2 activities

Inhibitors of the proteasome have been extensively studied for their applications in the treatment of human diseases such as hematologic malignancies, autoimmune disorders, and viral infections. Many of the proteasome inhibitors reported in the literature target the non-primed site of proteasome's substrate binding pocket. In this study, we designed, synthesized and characterized a series of novel α-keto phenylamide derivatives aimed at both the primed and non-primed sites of the proteasome. In these derivatives, different substituted phenyl groups at the head group targeting the primed site were incorporated in order to investigate their structure-activity relationship and optimize the potency of α-keto phenylamides. In addition, the biological effects of modifications at the cap moiety, P1, P2 and P3 side chain positions were explored. Many derivatives displayed highly potent biological activities in proteasome inhibition and anticancer activity against a panel of six cancer cell lines, which were further rationalized by molecular modeling analyses. Furthermore, a representative α-ketoamide derivative was tested and found to be active in inhibiting the cellular infection of SARS-CoV-2 which causes the COVID-19 pandemic. These results demonstrate that this new class of α-ketoamide derivatives are potent anticancer agents and provide experimental evidence of the anti-SARS-CoV-2 effect by one of them, thus suggesting a possible new lead to develop antiviral therapeutics for COVID-19.

Engineered Substrate for Cyclooxygenase-2: A Pentapeptide Isoconformational to Arachidonic Acid for Managing Inflammation

Beyond the conventional mode of working of anti-inflammatory agents through enzyme inhibition, herein, COX-2 was provided with an alternate substrate. A proline-centered pentapeptide isoconformational to arachidonic acid, which exhibited appreciable selectivity for COX-2, overcoming acetic acid- and formalin-induced pain in rats to almost 80%, was treated as a substrate by the enzyme. Remarkably, COX-2 metabolized the pentapeptide into small fragments consisting mainly of di- and tripeptides that ensured the safe breakdown of the peptide under in vivo conditions. The kinetic parameter Kcat/Km for COX-2-mediated metabolism of the peptide (6.3 × 105 M-1 s-1) was quite similar to 9.5 × 105 M-1 s-1 for arachidonic acid. Evidenced by the molecular dynamic studies and the use of Y385F COX-2, it was observed that the breakage of the pentapeptide has probably been taken place through H-bond activation of the peptide bond by the side chains of Y385 and S530.

Convenient green preparation of dipeptides using unprotected α-amino acids

Dipeptides and amides were obtained in high yields from N-carbobenzyloxy α-amino acids and 3-phenylpropanoic acid with unprotected α-amino acids via the corresponding mixed carbonic carboxylic anhydrides using ethyl chloroformate and triethylamine by an ecological and convenient method in which the protection of C-terminals is not needed.

Peptiligase, an Enzyme for Efficient Chemoenzymatic Peptide Synthesis and Cyclization in Water

We describe a novel, organic cosolvent-stable and cation-independent engineered enzyme for peptide coupling reactions. The enzyme is a variant of a stable calcium-independent mutant of subtilisin BPN′, with the catalytic Ser212 mutated to Cys and Pro216 converted to Ala. The enzyme, called peptiligase, catalyzes exceptionally efficient peptide coupling in water with a surprisingly high synthesis over hydrolysis (S/H) ratio. The S/H ratio of the peptide ligation reaction is correlated to the length of the peptide substrate and proved to be >100 for the synthesis of a 13-mer peptide, which corresponds to >99% conversion to the ligated peptide product and 1% hydrolytic side-reaction. Furthermore, peptiligase does not require a particular recognition motif resulting in a broadly applicable and traceless peptide ligation technology. Peptiligase is very robust, easy to produce in Bacillus subtilis, and its purification is straightforward. It shows good activity and stability in the presence of organic cosolvents and chelating or denaturing agents, enabling the ligation of poorly soluble (hydrophobic) or folded peptides. This enzyme could be useful for the (industrial) synthesis of diverse (pharmaceutical) peptides. In addition, peptiligase is able to efficiently catalyze head-to-tail peptide cyclization reactions. (Figure presented.) .

A green route for the synthesis of a bitter-taste dipeptide combining biocatalysis, heterogeneous metal catalysis and magnetic nanoparticles

There is increasing demand for green technologies to produce high-solubility and low-toxicity compounds with potential application in the food industry. This study aimed to establish a clean, synthetic route for preparing the bitter-taste dipeptide Ala-Phe, a potential substitute for caffeine as a food additive. Synthesis of Z-Ala-Phe-OMe starting from Z-Ala-OH and HCl·Phe-OMe was catalysed by thermolysin at 50 °C in buffer (step 1). Z-Ala-Phe-OMe ester hydrolysis to give Z-Ala-Phe-OH at 37 °C in 30% acetonitrile/buffer was catalysed by α-bovine chymotrypsin (αCT), protease with esterase activity (step 2). Hydrogenation of Z-Ala-Phe to give the desired Ala-Phe was catalysed by C/Pd in methanol (step 3). Steps 2 and 3 were optimized by using the magnetically recoverable recycling enzyme Fe3O4@silica-αCT and the magnetically recoverable metal nanocatalyst Fe3O4@silica-Pd, respectively. This inspiring combination of technologies and the original results demonstrate the suitability of using enzymes, metal catalyst and magnetic nanoparticles for easy, economical, stereoselective, clean production of an important target compound. Besides, they add to the development of peptide chemistry and catalysis.

Synthesis, molecular docking and anticancer studies of peptides and iso-peptides

Chiral peptides and iso-peptides were synthesized in excellent yield by using benzotriazole mediated solution phase synthesis. Benzotriazole acted both as activating and leaving group, eliminating frequent use of protection and subsequent deprotection. The procedure was based on the hypothesis that epimerization should be suppressed in solution due to a faster coupling rate than SPPS. All the synthesized peptides complied with Lipinski's Ro5 except for the rotatable bonds. Inhibition of cell proliferation of cancer cell lines is one of the most commonly used methods to study the effectiveness of any anticancer agents. Synthesized peptides and iso-peptides were tested against three cancer cell lines (MCF-7, MDA-MB 231) to determine their anti-proliferative potential. NFkB was also determined. Molecular docking studies were also carried out to complement the experimental results.

A one-pot saponification-coupling sequence suitable for C-terminus peptide elongation using lithium carboxylates

An efficient procedure has been developed for the saponification of common peptide esters, followed by straightforward coupling of the lithium carboxylate. Adding some water to the reaction medium gave faster saponification and did not interfere with the coupling reagent. As peptide chemistry constitutes a major application of the amidation reaction, amino acid substrates were chosen for this study, monitoring both yields and epimerization of the peptides obtained. Georg Thieme Verlag Stuttgart New York.

Synthesis and antimalarial bioassay of quinine - peptide conjugates

Amino acid and peptide conjugates of quinine were synthesized using microwave irradiation in 52-95% yields using benzotriazole methodology. The majority of these conjugates retain in vitro antimalarial activity with IC50 values below 100 nm, similar to quinine.

Enzymatic synthesis of activated esters and their subsequent use in enzyme-based peptide synthesis

Chemoenzymatic peptide synthesis is potentially the most cost-efficient technology for the synthesis of short and medium-sized peptides. However, there are still some limitations when challenging peptides, e.g. containing sterically demanding acyl donors, non-proteinogenic amino acids or proline residues, are to be synthesized. To remedy these limitations, special ester moieties have been used that are specifically recognized by the enzyme, e.g. guanidinophenyl, carboxamidomethyl (Cam) or trifluoroethyl (Tfe) esters, which, unfortunately, are notoriously difficult to synthesize chemically. Herein, we demonstrate that Cam and Tfe esters are very useful for Alcalase-CLEA mediated peptide synthesis using sterically demanding and non-proteinogenic acyl donors as well as poor nucleophiles, and combinations thereof. Furthermore, these esters can be efficiently synthesized by using the lipase Cal-B or Alcalase-CLEA. Finally, it is shown that the ester synthesis by Cal-B and subsequent peptide synthesis by Alcalase-CLEA can be performed simultaneously using a two-enzyme-one-pot approach with glycolamide or 2,2,2-trifluoroethanol as additive.