16679-86-0

Upstream product

• 2018-66-8 Z-Leu-OH 
• 2577-90-4 methyl (2S)-2-amino-3-phenylpropanoate 
• 63-91-2 L-phenylalanine 
• 67-56-1 methanol 
• 13171-96-5 Cbz-Leu-Phe-NH₂ 
• 21685-51-8 D-phenylalanine methyl ester 
• 76863-45-1 (S)-benzyl (1-azido-4-methyl-1-oxopentan-2-yl)carbamate 
• 13033-84-6 D-phenylalanine methyl ester hydrochloride 
• 102-82-9 tributyl-amine 
• 541-41-3 chloroformic acid ethyl ester 
• 186581-53-3 diazomethane 
• 104944-21-0 Z-S-Leu-R-Phe-OH 
• 13734-34-4 N-tert-butoxycarbonyl-L-phenylalanine 
• 66179-55-3 (S)-(1-hydroxycarbamoyl-3-methyl-butyl)-carbamic acid benzyl ester 

Downstream Products

• 16817-66-6 benzyl ((S)-1-(((S)-1-hydrazinyl-1-oxo-3-phenylpropan-2-yl)amino)-4-methyl-1-oxopentan-2-yl)carbamate 
• 6401-63-4 N-benzyloxycarbonyl-L-leucyl-L-phenylalanine 
• 38155-18-9 L-leucyl-L-phenylalanine methyl ester 
• 79259-43-1 Z-Leu-Phe-Leu-NH₂ 
• 13171-96-5 Cbz-Leu-Phe-NH₂ 
• 16748-67-7 H-L-Leu-L-Phe-OMe*HBr 
• 73870-97-0 α,δ-Di-Z-L-Orn-L-Leu-L-Phe-OMe 
• 97800-93-6 N-[(S)-1-((S)-1-Carbamoyl-2-phenyl-ethylcarbamoyl)-3-methyl-butyl]-nicotinamide 
• 97813-51-9 (S)-2-{(S)-4-Methyl-2-[(pyridine-3-carbonyl)-amino]-pentanoylamino}-3-phenyl-propionic acid methyl ester 
• 97800-72-1 1-Benzyl-3-[(S)-1-((S)-1-carbamoyl-2-phenyl-ethylcarbamoyl)-3-methyl-butylcarbamoyl]-pyridinium; bromide 
• 60079-69-8 N-(benzyloxycarbonyl)-L-leucyl-L-phenylalanine methylamide 
• 104944-21-0 Z-S-Leu-R-Phe-OH 
• 73870-98-1 α,δ-Di-Z-L-Orn-L-Leu-D-Phe-OMe 
• 75319-54-9 Z-L-Leu-D-Phe-L-Pro-L-Val-OMe 

Relevant academic research and scientific papers

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.

Amide and Peptide Bond Formation in Water at Room Temperature

A general and environmentally responsible method for the formation of amide/peptide bonds in an aqueous micellar medium is described. Use of uronium salt (1-cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylaminomorpholinocarbenium hexafluorophosphate (COMU) as a coupling reagent, 2,6-lutidine, and TPGS-750-M represents mild conditions associated with these valuable types of couplings. The aqueous reaction medium is recyclable leading to low E Factors.

Iodine-Mediated Oxidative Coupling of Hydroxamic Acids with Amines towards a New Peptide-Bond Formation

An efficient and straightforward approach for the coupling of Nα-protected hydroxamic acids with an amino component in the presence of iodine is delineated. The reaction is mediated by the formation of unstable but reactive acyl nitroso intermediates. The peptide hydroxamic acids were found to be useful substrates in coupling reactions.

Synthesis, bioactivity, docking and molecular dynamics studies of furan-based peptides as 20s proteasome inhibitors

Proteasome inhibitors are promising compounds for a number of therapies, including cardiovascular and eye diseases, diabetes, and cancers. We previously reported a series of furanbased peptidic inhibitors with moderate potencies against the proteasome b5 subunit, hypothesizing that the C-terminal furyl ketone motif could form a covalent bond with the catalytic residue, threonine 1. In this context, we describe further optimizations of the furan-based peptides, and a series of dipeptidic and tripeptidic inhibitors were designed and synthesized, aiming at improved potency and better solubility. Most of the tripeptidic inhibitors demonstrated improved potency and selectivity as b5 subunit inhibitors in both enzymatic and cellular assays, and good antineoplastic activities in various tumor cell lines were also observed. However, no inhibitory effects were observed for the dipeptidic compounds, which led us to presume that a noncovalent binding mode is adopted. Docking studies and molecular dynamics simulations were carried out to verify this presumption, with results showing that the distance between the furyl ketone motif and Thr1 is slightly too long to form covalent bond.

One-step C-terminal deprotection and activation of peptides with peptide amidase from stenotrophomonas maltophilia in neat organic solvent

Chemoenzymatic peptide synthesis is a rapidly developing technology for cost effective peptide production on a large scale. As an alternative to the traditional C→N strategy, which employs expensive N-protected building blocks in each step, we have investigated an N→C extension route that is based on activation of a peptide C-terminal amide protecting group to the corresponding methyl ester. We found that this conversion is efficiently catalysed by Stenotrophomonas maltophilia peptide amidase in neat organic media. The system excludes the possibility of internal peptide cleavage as the enzyme lacks intrinsic protease activity. The produced peptide methyl ester was used for peptide chain extension in a kinetically controlled reaction by a thermostable protease.

Bis(4,6-dimethoxy-1,3,5-triazin-2-yl) ether as coupling reagent for peptide synthesis

Bis(4,6-dimethoxy-1,3,5-triazin-2-yl) ether (4) was prepared by treatment of 2-hydroxy-4,6-dimethoxy-1,3,5-triazine with 2-chloro-4,6-dimethoxy-1,3,5- triazine in 61% yield. Ether 4, isoelectronic with pyrocarbonates, was found capable to activate carboxylic acids in the presence of 1,4-diazabicyclo[2.2.2] octane (DABCO) to yield, under mild reaction conditions, superactive triazine esters. Versatility of this new coupling reagent was confirmed by condensation of lipophilic and sterically hindered carboxylic acids with amines in 71-98% yield, and by synthesis of peptides, including those containing Aib-Aib sequence, in solution with high yield and high enantiomeric purity. Copyright

Synthesis of selenoxo peptides and oligoselenoxo peptides employing LiAlHSeH

Synthesis of selenoxo peptides by the treatment of Nα- protected peptide esters with a combination of PCl5 and LiAlHSeH is delineated. The method is simple, high-yielding, and free from racemization. Thus obtained selenoxo peptides are used as units for N-terminal chain extension through Nα-deprotection/coupling to yield peptide-selenoxo peptide hybrids. Multiple selenation is demonstrated by conversion of two peptide bonds of tripeptides into selenoxo peptide bonds. Amino acid derived arylamides are also converted into aryl selenoamides. C6H 5-CSeNH-Val-OMe 8f is obtained as single crystal, and its structure was determined through X-ray diffraction study.

Peptidyl 3-substituted 1-hydroxyureas as isosteric analogues of succinylhydroxamate MMP inhibitors

To evaluate N-hydroxyurea as zinc binding group in the design of MMP inhibitors, two peptidyl 1-hydroxyureas were prepared by N-hydroxycarbamoylation of the diastereomeric dipeptides H-Leu-Phe-NHMe and H-d-Leu-Phe-NHMe. Peptidyl 1-hydroxyureas were more potent than the parent peptides, but dramatically weaker (4-5 orders of magnitude) than the isosteric (R)-succinylhydroxamate analogue, which displays IC50 in the range of nM vs MMP-1, -3, -7 and sub-nM vs MMP-2, -8, and -9. The peptidyl 1-hydroxyurea 1a attained an IC50 of 20 μM vs MMP-9, and substantially approaches inhibition of known N-hydroxyureas based on aminoacids or peptides against other zinc metalloenzymes and non-peptidic N-hydroxyureas against MMPs. Strong preference of the O-N1-C{double bond, long}O unit for the antiperiplanar amide bond conformation seems to be the major limit for more effective zinc chelation. Methylation of a peptidyl 1-hydroxyurea at N3, to promote the synperiplanar O-N1-C{double bond, long}O conformation required for zinc chelation and improve affinity, resulted in release of a methylimidazolidine-2,4-dione through an undesired intramolecular reaction reminiscent of the Edman peptide degradation.

Amino acid fluorides: Their preparation and use in peptide synthesis

Z or Fmoc amino acid fluorides have been prepared from the protected amino acids and cyanuric fluoride, and have been tested both in the condensation with simple amino acid esters and in Solid Phase Peptide Synthesis.