646532-81-2

Basic information

• Product Name: L-Threonine, N-[(phenylmethoxy)carbonyl]-L-leucyl-L-a-glutamyl-, 2-(1,1-dimethylethyl) ester, 3-[2-[2-(1,1-dimethylethoxy)-2-oxoethyl]hydrazide]
• CAS NO: 646532-81-2
• Molecular Formula: C33H53N5O10
• Molecular Weight: 679.811
• Mol File: 646532-81-2.mol

Chemical Properties

• CAS DataBase Reference: L-Threonine, N-[(phenylmethoxy)carbonyl]-L-leucyl-L-a-glutamyl-, 2-(1,1-dimethylethyl) ester, 3-[2-[2-(1,1-dimethylethoxy)-2-oxoethyl]hydrazide](CAS DataBase Reference)
• NIST Chemistry Reference: L-Threonine, N-[(phenylmethoxy)carbonyl]-L-leucyl-L-a-glutamyl-, 2-(1,1-dimethylethyl) ester, 3-[2-[2-(1,1-dimethylethoxy)-2-oxoethyl]hydrazide](646532-81-2)
• EPA Substance Registry System: L-Threonine, N-[(phenylmethoxy)carbonyl]-L-leucyl-L-a-glutamyl-, 2-(1,1-dimethylethyl) ester, 3-[2-[2-(1,1-dimethylethoxy)-2-oxoethyl]hydrazide](646532-81-2)

Safety Data

• Hazardous Substances Data: 646532-81-2(Hazardous Substances Data)

Upstream product

• 5292-43-3 bromoacetic acid tert-butyl ester 
• 646532-72-1 Cbz-Leu-Glu(O-t-Bu)-Thr-NHNH₂ 

Downstream Products

• 685543-84-4 3-(N'-{2-[2-(2-benzyloxycarbonylamino-4-methyl-pentanoylamino)-4-tert-butoxycarbonyl-butyrylamino]-3-hydroxy-butyryl}-N-tert-butoxycarbonylmethyl-hydrazinocarbonyl)-acrylic acid ethyl ester 
• 685543-85-5 3-(N'-{2-[2-(2-benzyloxycarbonylamino-4-methyl-pentanoylamino)-4-tert-butoxycarbonyl-butyrylamino]-3-hydroxy-butyryl}-N-tert-butoxycarbonylmethyl-hydrazinocarbonyl)-acrylic acid benzyl ester 
• 646532-29-8 3-(N'-{2-[2-(2-benzyloxycarbonylamino-4-methyl-pentanoylamino)-4-tert-butoxycarbonyl-butyrylamino]-3-hydroxy-butyryl}-N-tert-butoxycarbonylmethyl-hydrazinocarbonyl)-oxirane-2-carboxylic acid benzyl ester 
• 646531-92-2 3-(N'-{2-[2-(2-benzyloxycarbonylamino-4-methyl-pentanoylamino)-4-tert-butoxycarbonyl-butyrylamino]-3-hydroxy-butyryl}-N-tert-butoxycarbonylmethyl-hydrazinocarbonyl)-oxirane-2-carboxylic acid ethyl ester 
• 646531-04-6 (2R,3R)-3-(N²-(N-benzyloxycarbonylleucyl-tert-butoxyglutamylthreonyl)-N¹-tert-butoxycarbonylmethylhydrazinocarbonyl)oxirane-2-carboxylic acid ethyl ester 
• 685543-86-6 4-(1-{N'-[3-(benzyl-methyl-carbamoyl)-acryloyl]-N'-tert-butoxycarbonylmethyl-hydrazinocarbonyl}-2-hydroxy-propylcarbamoyl)-4-(2-benzyloxycarbonylamino-4-methyl-pentanoylamino)-butyric acid tert-butyl ester 
• 646532-30-1 4-(2-benzyloxycarbonylamino-4-methyl-pentanoylamino)-4-{1-[N'-tert-butoxycarbonylmethyl-N'-(3-phenethylcarbamoyl-oxiranecarbonyl)-hydrazinocarbonyl]-2-hydroxy-propylcarbamoyl}-butyric acid tert-butyl ester 
• 646532-31-2 4-(1-{N'-[3-(1-benzylcarbamoyl-ethylcarbamoyl)-oxiranecarbonyl]-N'-tert-butoxycarbonylmethyl-hydrazinocarbonyl}-2-hydroxy-propylcarbamoyl)-4-(2-benzyloxycarbonylamino-4-methyl-pentanoylamino)-butyric acid tert-butyl ester 

Relevant articles and documents

Design, synthesis, and evaluation of aza-peptide Michael acceptors as selective and potent inhibitors of caspases-2, -3, -6, -7, -8, -9, and -10

Aza-peptide Michael acceptors are a novel class of inhibitors that are potent and specific for caspases-2, -3, -6, -7, -8, -9, and -10. The second-order rate constants are in the order of 106 M-1 s-1. The aza-peptide Michael acceptor inhibitor 18t (Cbz-Asp-Glu-Val-AAsp-trans-CH=CH-CON(CH2-1-Naphth)2 is the most potent compound and it inhibits caspase-3 with a k2 value of 5620000 M-1 s-1. The inhibitor 18t is 13700, 190, 6.4, 594, 37500, and 173-fold more selective for caspase-3 over caspases-2, -6, -7, -8, -9, and -10, respectively. Aza-peptide Michael acceptors designed with caspase specific sequences are selective and do not show any cross reactivity with clan CA cysteine proteases such as papain, cathepsin B, and calpains. High-resolution crystal structures of caspase-3 and caspase-8 in complex with aza-peptide Michael acceptor inhibitors demonstrate the nucleophilic attack on C2 and provide insight into the selectivity and potency of the inhibitors with respect to the P1′ moiety.

Aza-Peptide Michael Acceptors: A New Class of Inhibitors Specific for Caspases and Other Clan CD Cysteine Proteases

Aza-peptide Michael acceptors are a new class of irreversible inhibitors that are highly potent and specific for clan CD cysteine proteases. The aza-Asp derivatives were specific for caspases, while aza-Asn derivatives were effective legumain inhibitors. Aza-Lys and aza-Orn derivatives were potent inhibitors of gingipain K and clostripain. Aza-peptide Michael acceptors showed no cross reactivity toward papain, cathepsin B, and calpain.

Design, Synthesis, and Evaluation of Aza-Peptide Epoxides as Selective and Potent Inhibitors of Caspases-1, -3, -6, and -8

Aza-peptide epoxides, a novel class of irreversible protease inhibitors, are specific for the clan CD cysteine proteases. Aza-peptide epoxides with an aza-Asp residue at P1 are excellent irreversible inhibitors of caspases-1, -3, -6, and -8 with second-order inhibition rates up to 1 910 000 M-1 s-1. In general, the order of reactivity of aza-peptide epoxides is S,S > R,R > trans > cis. Interestingly, some of the R,R epoxides while being less potent are actually more selective than the S,S epoxides. Our aza-peptide epoxides designed for caspases are stable, potent, and specific inhibitors, as they show little to no inhibition of other proteases such as the aspartyl proteases porcine pepsin, human cathepsin D, plasmepsin 2 from P. falciparum, HIV-1 protease, and the secreted aspartic proteinase 2 (SAP-2) from Candida albicans; the serine proteases granzyme B and α-chymotrypsin; and the cysteine proteases cathepsin B and papain (clan CA), and legumain (clan CD).

Aza-peptide epoxides: A new class of inhibitors selective for clan CD cysteine proteases

Aza-peptide epoxides, a new class of irreversible protease inhibitors, are specific for the clan CD cysteine proteases. The inhibitors have second-order rate constants up to 105 M-1 s-1, with the most potent epoxides having the S,S stereochemistry. The aza-Asn derivatives are effective legumain inhibitors, while the aza-Asp epoxides were specific for caspases. The inhibitors have little or no inhibition with other proteases such as chymotrypsin, papain, or cathepsin B.