77066-56-9

Upstream product

• 13734-34-4 N-tert-butoxycarbonyl-L-phenylalanine 
• 1738-77-8 L-leucine benzyl ester p-toluenesulfonate 
• 74193-68-3 N-tert-butyloxycarbonyl-L-phenylalanyl-L-leucine benzyl ester 
• 76-05-1 trifluoroacetic acid 

Downstream Products

• 73994-88-4 Boc-Gly-Phe-Leu-OBzl 
• 81678-16-2 leucine enkephalin acetate 
• 69729-16-4 N-benzyloxycarbonyl-L-tyrosyl-glycyl-glycyl-L-phenylalanyl-L-leucine benzyl ester 

Relevant academic research and scientific papers

New cysteine protease inhibitors: Electrophilic (Het)arenes and unexpected prodrug identification for the trypanosoma protease rhodesain

Electrophilic (het)arenes can undergo reactions with nucleophiles yielding π- or Meisenheimer (σ-) complexes or the products of the SNAr addition/elimination reactions. Such building blocks have only rarely been employed for the design of enzyme inhibitors. Herein, we demonstrate the combination of a peptidic recognition sequence with such electrophilic (het)arenes to generate highly active inhibitors of disease-relevant proteases. We further elucidate an unexpected mode of action for the trypanosomal protease rhodesain using NMR spectroscopy and mass spectrometry, enzyme kinetics and various types of simulations. After hydrolysis of an ester function in the recognition sequence of a weakly active prodrug inhibitor, the liberated carboxylic acid represents a highly potent inhibitor of rhodesain (Ki = 4.0 nM). The simulations indicate that, after the cleavage of the ester, the carboxylic acid leaves the active site and re-binds to the enzyme in an orientation that allows the formation of a very stable π-complex between the catalytic dyad (Cys-25/His-162) of rhodesain and the electrophilic aromatic moiety. The reversible inhibition mode results because the SNAr reaction, which is found in an alkaline solvent containing a low molecular weight thiol, is hindered within the enzyme due to the presence of the positively charged imidazolium ring of His-162. Comparisons between measured and calculated NMR shifts support this interpretation.

Naphthoquinones as covalent reversible inhibitors of cysteine proteases—studies on inhibition mechanism and kinetics

The facile synthesis and detailed investigation of a class of highly potent protease inhibitors based on 1,4‐naphthoquinones with a dipeptidic recognition motif (HN‐L‐Phe‐L‐Leu‐OR) in the 2‐position and an electron‐withdrawing group (EWG) in the 3‐positio

Preparation and conformational study of CF3-containing enkephalin-derived oligopeptide

Incorporation of (2S,3S)-4,4,4-trifluorothreonine (F3-Thr) instead of Thr in the enkephalin-derived hexapeptide led to the apparent conformational alteration due to the strong electron-withdrawing effect of the trifluoromethyl group by comparison with the original compound on the basis of their various NMR measurements.