77443-49-3

Upstream product

• 34619-03-9 tert-butyldicarbonate 
• 77935-37-6 Benzyl L-valyl-L-valinate hydrochloride 
• 21760-98-5 L-valine benzyl ester 
• 66866-46-4 C₁₅H₂₇NO₆ 
• 16652-76-9 L-valine benzyl ester p-toluenesulfonate salt 
• 122751-34-2 Boc-Val-OPyCl 
• 33857-88-4 (S)-methyl 2-((S)-2-(tert-butoxycarbonylamino)-3-methylbutanamido)-3-methylbutanoate 
• 100-51-6 benzyl alcohol 
• 13734-41-3 t-Boc-L-valine 
• 2462-34-2 L-valine benzyl ester hydrochloride 
• 65138-05-8 (S)-2-hydroxy-3-methylbutyric acid benzyl ester 
• 66447-55-0 ((S)-1-benzylcarbamoyl-2-methyl-propyl)-carbamic acid tert-butyl ester 
• 72-18-4 L-valine 
• 138892-16-7 (S)-2-[(S)-2-(Benzhydrylidene-amino)-3-methyl-butyrylamino]-3-methyl-butyric acid benzyl ester 

Downstream Products

• 122299-14-3 H-Thr-Asn-Val-Val-OH 
• 133898-41-6 Boc-Asn-Val-Val-OBzl 
• 133898-42-7 Z-Thr-Asn-Val-Val-OBzl 
• 149836-38-4 Z-Gly-Pro-Arg(NO₂)-Val-Val-OBzl 
• 149836-40-8 Z(OMe)-Arg(NO₂)-Val-Val-OBzl 
• 99429-52-4 Val-Val-Val-OBzl 
• 111052-94-9 Z-Gly-Gly-Val-Val-Val-OBzl 
• 111052-95-0 Boc-Val-Val-Val-Gly-Gly-OBzl 
• 99429-50-2 Boc-Val-Val-Val-OBzl 
• 3918-94-3 Val-Val 
• 69209-72-9 (N-tert-butoxycarbonyl-L-valyl)-L-valine 

Relevant academic research and scientific papers

Design, synthesis and biological evaluation of dipeptides as novel non-covalent 20S proteasome inhibitors

Based on the interaction modes of the natural 20S proteasome inhibitors TMC-95A, we have previously discovered a dipeptide 1. To explore the SAR around compound 1, we designed and synthesized a series of dipeptides (8–38) with a fragment-based strategy. Among them, nine compounds showed significant inhibitory activities against the chymotrypsin-like activity of human 20S proteasome with IC50 values at the submicromolar level, which were comparable or even superior to the parent compound 1. Meanwhile, they displayed no significant inhibition against trypsin-like and caspase-like activities of 20S proteasome. The results suggested the feasibility to design dipeptides as novel and potent 20S proteasome inhibitors. (Figure presented.).

TRANSGLUTAMINASE 2 (TG2) INHIBITORS

Described herein are compounds and pharmaceutical compositions containing such compounds which inhibit transglutaminase 2 (TG2). Also described herein are methods for using such TG2 inhibitors, alone or in combination with other compounds, for treating diseases or conditions that would benefit from TG2 inhibition.

Design, synthesis, and evaluation of cystargolide-based β-lactones as potent proteasome inhibitors

The peptidic β-lactone proteasome inhibitors (PIs) cystargolides A and B were used to conduct structure-activity relationship (SAR) studies in order to assess their anticancer potential. A total of 24 different analogs were designed, synthesized and evaluated for proteasome inhibition, for cytotoxicity towards several cancer cell lines, and for their ability to enter intact cells. X-ray crystallographic analysis and subunit selectivity was used to determine the specific subunit binding associated with the structural modification of the β-lactone (P1), peptidic core, (Px and Py), and end-cap (Pz) of our scaffold. The cystargolide derivative 5k, structurally unique at both Py and P1, exhibited the most promising inhibitory activity for the β5 subunit of human proteasomes (IC50 = 3.1 nM) and significant cytotoxicity towards MCF-7 (IC50 = 416 nM), MDA-MB-231 (IC50 = 74 nM) and RPMI 8226 (IC50 = 41 nM) cancer cell lines. Cellular infiltration assays revealed that minor structural modifications have significant effects on the ability of our PIs to inhibit intracellular proteasomes, and we identified 5k as a promising candidate for continued therapeutic studies. Our novel drug lead 5k is a more potent proteasome inhibitor than carfilzomib with mid-to-low nanomolar IC50 measurements and it is cytotoxic against multiple cancer cell lines at levels approaching those of carfilzomib.

Total synthesis and absolute stereochemistry of the proteasome inhibitors cystargolides A and B

The absolute stereochemistry of the cystargolides was determined by total synthesis. Evaluation of synthetic cystargolides and derivatives showed that the natural (2S,3R) stereochemistry is essential for activity. Moreover, benzyl esters (-)-10 and (-)-15

Development of supramolecular organo-gel based on tripeptide skeletons

Boc-Ser-Val-Gly-OCH2Ph (31) showed high gelation abilities in the aromatic solvents, particularly in toluene. The minimum gelation concentration of 31 in toluene was 10 mg/ml, suggesting that 2500 molecules of toluene were immobilized by each m

A mild Boc deprotection and the importance of a free carboxylate

We report a facile and rapid removal of Boc protecting groups using microwave heating in H2O, with deprotection only requiring a free carboxylic acid group in the starting material. Unlike previous approaches, no additional reagents are required.

Self-assembled monolayer of a pepstatin fragment as a sensing element for aspartyl proteases

A novel disulfide, which carried two pepstatin fragments at both ends, was prepared by the coupling of 11,11′-dithiobisundecanoic acid (DTUA) with a fragment (Val-Val-Sta) carrying a n-hexyl end (Pepsta(h)). The compound obtained (DTUA-Pepsta(h)) formed a

Simplified pepstatins: Synthesis and evaluation of N-terminally modified analogues

The promising strategy of gastric ulcer healing with perorally administered epidermal growth factor (EGF) is so far strongly limited by the pepsinic degradation of this therapeutic polypeptide in the stomach. The incorporation of EGF in a bioadhesive polymer-pepsin inhibitor conjugate used as drug carrier matrix, however, might provide sufficient protection toward pepsinic degradation. The synthesis of appropriate pepsin inhibitors represents a prerequisite for the development of such polymer-inhibitor conjugates. The presented study demonstrates that modifications at the N- terminus of simplified analogues of pepstatin which can be synthesized in a simple and straight way result only in slight variations of the inhibitory activity. These analogues display only 10-fold reduced inhibitory activity, compared to pepstatin A, when bearing a greater N-terminal group like isovaleryl, Boc, or Cbz. Compounds which are substituted at the N-terminus by a shorter N-acyl group like propionyl or cyclopropylcarbonyl show further reduced activity (0.01, compared to pepstatin A). The presence of an amide or a urethane moiety at the N-terminus has no considerable effect on enzyme inhibition. Therefore, the N-terminus of these analogues is able to be modified forming a covalent bond to various bioadhesive polymers via a suitable functionality.

Amino acids and peptides. XVII. Synthesis of peptides related to N-terminal portion of fibrin alpha-chain and their inhibitory effect on fibrinogen/thrombin clotting.

Various peptides related to N-terminal portion of fibrin alpha-chain were synthesized by the solution method and the solid-phase method, and their inhibitory effect on fibrinogen/thrombin clotting was examined. Extension of peptide chain from N-terminal t