7801-71-0

Basic information

• Product Name: Z-LEU-LEU-OH
• Synonyms: N-CARBOBENZOXY-L-LEUCYL-L-LEUCINE;Z-LEU-LEU-OH;Z-L-LEUCYL-L-LEUCINE;CBZ-L-LEU-L-LEU;N-[N-(benzyloxycarbonyl)-L-leucyl]-L-leucine;Cbz-L-Leu-L-Leu-OH;Z-L-Leu-L-Leu-OH;(S)-2-((S)-2-(((Benzyloxy)carbonyl)aMino)-4-MethylpentanaMido)-4-Methylpentanoic acid
• CAS NO: 7801-71-0
• Molecular Formula: C₂₀H₃₀N₂O₅
• Molecular Weight: 378.46
• EINECS: 232-258-7
• Mol File: 7801-71-0.mol

Chemical Properties

• Boiling Point: 598°Cat760mmHg
• Flash Point: 315.5°C
• Appearance: /
• Density: 1.13g/cm³
• Vapor Pressure: 3.77E-15mmHg at 25°C
• Refractive Index: 1.52
• Storage Temp.: -15°C
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• CAS DataBase Reference: Z-LEU-LEU-OH(CAS DataBase Reference)
• NIST Chemistry Reference: Z-LEU-LEU-OH(7801-71-0)
• EPA Substance Registry System: Z-LEU-LEU-OH(7801-71-0)

Safety Data

• Hazardous Substances Data: 7801-71-0(Hazardous Substances Data)

Usage

InChI:InChI=1/C20H30N2O5/c1-13(2)10-16(18(23)21-17(19(24)25)11-14(3)4)22-20(26)27-12-15-8-6-5-7-9-15/h5-9,13-14,16-17H,10-12H2,1-4H3,(H,21,23)(H,22,26)(H,24,25)

Upstream product

• 3504-37-8 Cbz-L-Leu-L-Leu-OMe 
• 7797-39-9 Z-L-Leucin-<5-chlor-chinolyl-(8)-ester> 
• 61-90-5 L-leucine 
• 2018-66-8 Z-Leu-OH 
• 13139-15-6 N-tert-butoxycarbonyl-L-leucine 
• 2666-93-5 (S)-Leu-OMe 
• 51021-87-5 N-benzyloxycarbonyl-L-leucine methyl ester 
• 7517-19-3 methyl (L)-leucinate hydrochloride 
• 40162-58-1 Z-Leu-Leu-OtBu 
• 71800-39-0 N-benzyloxycarbonylated amide of L-leucylleucine 
• 64187-29-7 Z-L-Leu-OCH₂CN 
• 3397-35-1 Z-L-leucine hydroxysuccinimide ester 

Downstream Products

• 3303-31-9 L-leucyl-L-leucine 
• 24210-21-7 Z-Leu-Leu-Val-Phe-OCH₃ 
• 106561-18-6 N-(benzyloxycarbonyl)-L-leucyl-L-leucyl-L-leucine methyl ester 
• 98695-41-1 N-carbobenzoxy-L-leucyl-L-leucyl-L-leucyl-L-leucyl-L-leucine methyl ester 

Relevant articles and documents

Light-Controlled Cell-Cycle Arrest and Apoptosis

Cell-cycle interference by small molecules has widely been used to study fundamental biological mechanisms and to treat a great variety of diseases, most notably cancer. However, at present only limited possibilities exist for spatio-temporal control of the cell cycle. Here we report on a photocaging strategy to reversibly arrest the cell cycle at metaphase or induce apoptosis using blue-light irradiation. The versatile proteasome inhibitor MG132 is photocaged directly at the reactive aldehyde function effectively masking its biological activity. Upon irradiation reversible cell-cycle arrest in the metaphase is demonstrated to take place in vivo. Similarly, apoptosis can efficiently be induced by irradiation of human cancer cells. With the developed photopharmacological approach spatio-temporal control of the cell cycle is thus enabled with very high modulation, as caged MG132 shows no effect on proliferation in the dark. In addition, full compatibility of photo-controlled uncaging with dynamic microscopy techniques in vivo is demonstrated. This visible-light responsive tool should be of great value for biological as well as medicinal approaches in need of high-precision targeting of the proteasome and thereby the cell cycle and apoptosis.

Application of proteasome inhibitor in inhibition of novel coronavirus

The invention provides application of a proteasome inhibitor in inhibition of a novel coronavirus or preparation of novel coronavirus inhibitors. The proteasome inhibitor has a structure represented by a formula (I) or isomers, pharmaceutically acceptable salts thereof and prodrugs thereof. According to the application, by applying the proteasome inhibitor to inhibition of the novel coronavirus, good inhibiting activity is obtained, and a novel treatment way of think is provided for diseases such as pneumonia caused by the novel coronavirus.

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.

Tripeptide analogues of MG132 as protease inhibitors

The 26S proteasome and calpain are linked to a number of important human diseases. Here, we report a series of analogues of the prototypical tripeptide aldehyde inhibitor MG132 that show a unique combination of high activity and selectivity for calpains over proteasome. Tripeptide aldehydes (1–3) with an aromatic P3 substituent show enhanced activity and selectivity against ovine calpain 2 relative to chymotrypsin-like activity of proteasome. Docking studies reveal the key contacts between inhibitors and calpain to confirm the importance of the S3 pocket with respect to selectivity between calpains 1 and 2 and the proteasome.

AZA-PEPTIDE ALDEHYDES AND KETONES

The present disclosure relates to compositions for inhibiting proteases, methods for synthesizing the compositions, and methods of using the disclosed protease inhibitors. Aspects of the invention include aza-peptide aldehyde and ketone compositions that inhibit proteases. The disclosed compounds, pharmaceutically acceptable salts, pharmaceutically acceptable derivatives, prodrugs, or combinations thereof can be used to treat disease or pathological conditions related to the activity of proteases associated with a specific disease or condition.

Synthesis and biological activity of peptide proline-boronic acids as proteasome inhibitors

On the basis of the application of proline-boronic acid as pharmacophore in the kinase inhibitors and our previous research results, using proline-boronic acid as warhead, two series of peptide proline-boronic acids, dipeptide proline-boronic acids (I) and tripeptide proline-boronic acids (II), were designed and synthesized. All the synthesized compounds were first evaluated for their biological activity against MGC803 cell, and then, the best compound II-7 was selected to test its anti-tumor spectrum on six human tumor cell lines and proteasome inhibition against three subunits. The results indicated that series II have much better biological activities than series I. The compound II-7 exhibited not only excellent biological activities with IC50 values of nM level in both cell and proteasome models, but also much better subunit selectivity. Thus, proline-boronic acid as warhead is reasonable in the design of proteasome inhibitors.

Recyclable hypervalent iodine(III) reagent iodosodilactone as an efficient coupling reagent for direct esterification, amidation, and peptide coupling

A hypervalent iodine(III) reagent plays a novel role as an efficient coupling reagent to promote the direct condensation between carboxylic acids and alcohols or amines to provide esters, macrocyclic lactones, amides, as well as peptides without racemization. The regeneration of iodosodilactone (1) can also be readily achieved. The intermediate acyloxyphosphonium ion C from the activation of a carboxylic acid is thought to be involved in the present esterification reaction.

α,β-unsaturated N-Acylpyrrole peptidyl derivatives: New proteasome inhibitors

Because of the encouraging results obtained using vinyl ester derivatives, we synthesized and tested a novel series of peptide-based proteasome inhibitors bearing a new pharmacophore unit at the C-terminal. N-Acylpyrrole moiety is a potential substrate for Michael addition by catalytic threonine. Several analogues have demonstrated a selective inhibition of the multicatalytic complex β1 subunits, the capacity to permeate cellular membrane, and good pharmacokinetics properties.

Mixing of peptides and electrophilic traps gives rise to potent, broad-spectrum proteasome inhibitors

The synthesis and evaluation of hybrid proteasome inhibitors that contain structural elements of the known inhibitors bortezomib, epoxomicin and peptide vinyl sulfones is described. From the panel of 15 inhibitors some structure activity relationships can be deduced with regard to inhibitory activity in relation to peptide recognition element, inhibitor size and nature of the electrophilic trap. Further, the panel contains one of the most potent peptide-based pan-proteasome inhibitors reported to date. This journal is The Royal Society of Chemistry.

Proteasome inhibitors: Synthesis and activity of arecoline oxide tripeptide derivatives

We describe the synthesis and biological activities of a series of methyl 3,4-epoxypiperidine-3-carboxylate tripeptide derivatives that inhibit the chymotryptic and tryptic active sites of the 20S proteasome. Of the series, compound 2 which contains 3-hydroxy-2-methylbenzoyl group at its N-terminal position, displayed the greatest inhibitory potency (IC50 1 μM). All derivatives showed favourable pharmacokinetic properties.