3303-31-9

Usage

InChI:InChI=1/C12H24N2O3/c1-7(2)5-9(13)11(15)14-10(12(16)17)6-8(3)4/h7-10H,5-6,13H2,1-4H3,(H,14,15)(H,16,17)/t9-,10-/m0/s1

Upstream product

• 73401-65-7 (S)-2-((S)-2-tert-Butoxycarbonylamino-4-methyl-pentanoylamino)-4-methyl-pentanoic acid 
• 109068-10-2 N-(N-allyloxycarbonyl-L-leucyl)-L-leucine 
• 7801-71-0 N-benzyloxycarbonyl-L-leucyl-L-leucine 
• 24733-21-9 Pipoc-Leu-Leu 
• 77167-53-4 HCl*H-Leu₂-OBn 
• 2883-36-5 L-Leu-Leu 
• 3190-70-3 L-leucine N-carboxyanhydride 
• 2743-60-4 L-Leucine ethyl ester 
• 6297-57-0 (S)-4-methyl-2-(phenylmethylsulfonamido)pentanoic acid 
• 101437-29-0 N-allyloxycarbonyl-L-leucine-(N'-phenyl-hydrazide) 
• 102322-09-8 N-phenylmethanesulfonyl-L-leucine-(N'-phenyl-hydrazide) 
• 61-90-5 L-leucine 
• 72-18-4 L-valine 
• 3504-37-8 Cbz-L-Leu-L-Leu-OMe 

Downstream Products

• 98-10-2 benzenesulfonamide 
• 124-38-9 carbon dioxide 
• 590-86-3 isovaleraldehyde 
• 700372-68-5 Z-Leu-Leu-Leu-[methyl (3RS,4RS)-3,4-epoxypiperidine-3-carboxylate] 
• 6491-83-4 ((S)-2-amino-4-methylpentanoyl)-L-leucine methyl ester hydrochloride 
• 61-90-5 L-leucine 
• 17665-02-0 L-leucyl-D-leucine 
• 94683-09-7 ((S)-2-(1,3-dioxoisoindolin-2-yl)-4-methylpentanoyl)-L-leucine 
• 952-43-2 (3S,6S)-3,6-diisobutylpiperazine-2,5-dione 

Relevant academic research and scientific papers

First Steps for the Direct Purification of l -Leu- l -Leu Dipeptide through Co-Crystallization

Trifluoroacetate salt contamination of peptides represents a challenging issue related to solid phase peptide synthesis and purification because it affects the chemical and biological properties of peptides. Purification of such materials is typically performed through a two-step post-synthetic procedure based on chromatography followed by ion exchange. For the first time, co-crystallization is presented in this study as a possible alternative and advantageous single-step method for the obtaining of TFA-free crystals of a dipeptide. A trifluoroacetate-contaminated l-Leu-l-Leu dipeptide has been used for co-crystallization experiments along with different solid coformers. New multicomponent crystals containing only the title compound and the second co-crystal formers are described in this work. Such results represent a novelty in the field of peptide chemistry and a valid proof for the use of crystal engineering-based method for a combined purification and crystallization strategy.

A PROCESS FOR PREPARATION OF A PEPTIDE

The present invention relates to a novel process for preparation of peptides having amino acid chain length in the range of 2-40 comprises the steps: i) attaching an end-blocked amino acid with an ionic liquid based solid support in presence of an ionic solvent to obtain an end-terminal blocked amino acid attached ionic liquid; ii) removing end-terminal blocking agent from the end-terminal blocked amino acid attached ionic liquid of step i) followed by work up to obtain an amino acid attached ionic liquid; iii) repeating steps i) through ii) one or more times to obtain a polypeptide attached ionic liquid; and iv) detaching the polypeptide from the polypeptide attached ionic liquid of step iii) to obtain the polypeptide. Said process does not use any auxiliary reagents like dehydrating agent or activating agent. The use of ionic liquids as supports as well as solvents result in the faster kinetics of the process, the separation issues are reduced, and the process has no racemization issues.

Biomimetic epoxidation in aqueous media catalyzed by cyclic dipeptides

We have developed a practical epoxidation of electron-deficient enones in aqueous media using cyclic dipeptides as bioinspired green catalyst. Optimizing the reaction conditions in a triphasic system led to efficient conditions providing epoxides with good enantioselectivities. Depending on the catalyst substituent chirality, both enantiomers are obtained. The cyclic rigidity impacts significantly the enantioselectivity.

Cathepsin D activity and selectivity in the acidic conditions of a tumor microenvironment: Utilization in the development of a novel Cathepsin D substrate for simultaneous cancer diagnosis and therapy

Pro-Cathepsin D (pCD) is an aspartyl endopeptidase which is over expressed in many cancers. This over expression generally led to its secretion into the extracellular culture medium of cancer cells. Moreover, pCD can auto activate and cleave its substrates at an acidic pH compatible with that found in tumor microenvironments (TME). Thus, exploiting these two pathological characteristics of TME offers the opportunity to develop new protease-activated vector on the basis of their specific substrate structures. The aim of this study was to validate new pCD substrates in the extracellular pH conditions of TME. As a first step, we investigated the effect of pH on the catalytic activity and selectivity of mature Cathepsin D (CD). It was found that the increase in the pH of the media led to a decrease in the reaction rate. However, the specificity of mature CD was not affected by a variation in pH. In the second step, the effect of the substrate structure was studied. We demonstrated that the substrate structure had a significant effect on the catalytic activity of CD. In fact, some modifications in peptide structure induced a change in the catalytic behavior that involved a substrate activation phenomenon. We suggest that this activation may be related to the amphiphilic nature of the modified peptide that may induce an interfacial activation mechanism. Finally, pCD, which is the major form found in the extracellular culture medium of cancer cells, was used. We demonstrated that the proform of CD cleave the modified peptide 5 at pH 6.5 with the same cleavage selectivity obtained with the mature form of the protease. These data provide a better understanding of CD behavior in tumor microenvironment conditions and this knowledge can be used to develop more specific tools for diagnosis and drug delivery.

Champacyclin, a new cyclic octapeptide from Streptomyces strain C42 isolated from the Baltic Sea

New isolates of Streptomyces champavatii were isolated from marine sediments of the Gotland Deep (Baltic Sea), from the Urania Basin (Eastern Mediterranean), and from the Kiel Bight (Baltic Sea). The isolates produced several oligopeptidic secondary metabolites, including the new octapeptide champacyclin (1a) present in all three strains. Herein, we report on the isolation, structure elucidation and determination of the absolute stereochemistry of this isoleucine/leucine (Ile/Leu = Xle) rich cyclic octapeptide champacyclin (1a). As 2D nuclear magnetic resonance (NMR) spectroscopy could not fully resolve the structure of (1a), additional information on sequence and configuration of stereocenters were obtained by a combination of multi stage mass spectrometry (MSn) studies, amino acid analysis, partial hydrolysis and subsequent enantiomer analytics with gas chromatography positive chmical ionization/electron impact mass spectrometry (GC-PCI/EI-MS) supported by comparison to reference dipeptides. Proof of the head-to-tail cyclization of (1a) was accomplished by solid phase peptide synthesis (SPPS) compared to an alternatively side chain cyclized derivative (2). Champacyclin (1a) is likely synthesized by a non-ribosomal peptide synthetase (NRPS), because of high content of (D)-amino acids. The compound (1a) showed antimicrobial activity against the phytopathogen Erwinia amylovora causing the fire blight disease of certain plants.

A novel L-amino acid ligase from bacillus subtilis NBRC3134 catalyzed oligopeptide synthesis

L-Amino acid ligase catalyzes dipeptide synthesis from unprotected L-amino acids in an ATP-dependent manner. We have purified a new L-amino acid ligase, RizA, which synthesizes dipeptides whose N-terminus is Arg, from Bacillus subtilis NBRC3134, a microorganism that produces a rhizocticin peptide antibiotic. It was suggested that RizA is probably involved in rhizocticin biosynthesis. In this study, we performed sequence analysis of unknown regions around rizA, and newly identified a gene that encodes a protein that possesses an ATP-grasp motif upstream of rizA. This gene was designated rizB, and its recombinant protein was prepared. Recombinant RizB synthesized homo-oligo-mers of branched-chain L-amino acids and L-methionine consisting of two to five amino acids in an ATP-dependent manner. RizB also synthesized various heteropeptides. Further examination showed that RizB might elongate a peptide chain at the N-terminus. This is the first report on an L-amino acid ligase catalyzing oligopeptide synthesis.

DPP4 INHIBITOR AND PHARMACEUTICAL APPLICATION THEREOF

The present invention provides a Dpp4 inhibitor which comprises a leucine derivative of the following formula (1) or a methionine derivative of the following formula (2): wherein each R1 and R3 represents a hydrogen atom (H) and an L-amino acid residue; R2 represents a hydroxyl group (OH), alkoxy group having 1 to 6 carbon atoms, amino group (NH2), alkylamino group having 1 to 6 carbon atoms, glycine residue, β-alanine residue, L-amino acid (except for proline, alanine and phenylalanine) residue or L-amino-acid amide (except for proline amide, alanine amide and phenylalanine amide) residue; and R4 represents a hydroxyl group (OH), alkoxy group having 1 to 6 carbon atoms, amino group (NH2), alkylamino group having 1 to 6 carbon atoms, glycine residue, β-alanine residue, L-amino acid (except for proline and alanine) residue or L-amino-acid amide (except for proline amide and alanine amide) residue. These derivatives also act as autophagy regulators.

Mechanism study on the oligomerization of amino acids into peptides by phosphorus trichloride

As treated by phosphorus trichloride, amino acids could oligomerize into polypeptides. Based on the results obtained by 31P-NMR and ESI-MS/MS, a possible reaction mechanism was proposed. The mechanism might undergo a penta-coordinated phosphorus intermediat. The activated amino acid was a five-membered cyclic penta-coordinated phosphorus intermediate. The nucleophilic attack of the amino group from an amino acid or peptide on the carbonyl group of intermediate led to the formation of peptide and released one equivalent dichloride phosphoric acid. The repetition of the reaction sequence generated a series of oligopeptides. Copyright Taylor & Francis Group, LLC.

Convenient solid-phase synthesis of oligopeptides using pentacoordinated phosphoranes with amino acid residue as building blocks

The reactive intermediates of pentacoordinated phosphoranes with amino acids (P(5)-AA) as building blocks, which were obtained by the reaction of O-phenylene phosphorochloridate with N,O-bis(trimethylsilyl)amino acids, were linked to a solid-phase support containing a hydroxymethyl polystyrene functional group. The first amino acid residue was coupled to the solid-phase support after washing the resin with organic solvent. Repeating the procedure led to oligopeptides linked on the resin. A series of free oligopeptides including tetra-Gly, di-Val, tri-Val, di-Leu, di-Phe, and Phe-Leu were obtained after cleavage from solid-phase support. The structure of these oligopeptides were determined by IR, 1H NMR, FAB-MS, and HPLC.

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.