213487-91-3

Upstream product

• 186581-53-3 diazomethane 
• 66076-71-9 (Cbz-D,L-Homo-Cys-OH)₂ 
• 501-53-1 benzyl chloroformate 
• 147857-42-9 Dimethyl (2RS,2'RS)-homocystinate dihydrochloride 
• 462-10-2 DL-homocystine 

Downstream Products

• 224822-71-3 2-Benzyloxycarbonylamino-4-chlorosulfonyl-butyric acid methyl ester 
• 38869-96-4 (3RS)-3-[N-(Benzyloxycarbonyl)amino]-2-oxo-tetrahydrothiophene 
• 382601-87-8 Methyl (2RS)-N-(benzyloxycarbonyl)homocysteinate 
• 382601-88-9 Dimethyl (2RS)-2-[N-(benzyloxycarbonyl)amino]-6-oxo-5-thiapimelate 
• 134306-32-4 (+/-)-2-<(benzyloxycarbonyl)amino>butanoic acid methyl ester 

Relevant academic research and scientific papers

Synthesis and in vitro enzyme activity of aza, oxa and thia derivatives of bacterial cell wall biosynthesis intermediates

Mechanism based inhibitors of diaminopimelate aminotransferase (DAP-AT) were designed using knowledge of its substrate specificity and mechanism. Synthesis of thiolester and amide substrate analogues was achieved prior to in vitro inhibition studies, but ester analogues proved too unstable to isolate. Thia substrate analogues showed no inhibitory properties, but the aza substrate analogue 12a showed reversible inhibition vs. DAP-AT and time dependent inhibition in the absence of the natural substrate 4. Substrate analogue 12a is thefirst example of an amide inhibitor of PLP dependent enzymes. Antibiotic properties of 12a were also briefly assessed.

β-Amino-thiols inhibit the zinc metallopeptidase activity of tetanus toxin light chain

Tetanus neurotoxin is a 150-kDa protein produced by Clostridium tetani, which causes the lethal spastic paralytic syndromes of tetanus by blocking inhibitory neurotransmitter release at central synapses. The toxin light chain (50 kDa) has a zinc endopeptidase activity specific for synaptobrevin, an essential component of the neuroexocytosis apparatus. Previous unsuccessful attempts to block the proteolytic activity of this neurotoxin with well-known inhibitors of other zinc proteases led us to study the design of specific inhibitors as a possible drug therapy to prevent the progressive evolution of tetanus following infection. Starting from the synaptobrevin sequence at the level of the cleavage site by tetanus neurotoxin (Gln76- Phe77)a thiol analogue of glutamine demonstrated inhibitory activities in the millimolar range. A structure-activity relationship performed with this compound led us to determine the requirement for the correct positioning of the thiol group, the primary amino group, and a carboxamide or sulfonamide group on the side chain. This resulted in the design of a β-amino(4- sulfamoylphenyl)glycine-thiol, the first significantly efficient inhibitor of tetanus neurotoxin with a K(i) value of 35 ± 5μM.