Synthesis and evaluation of aza-peptidyl inhibitors of the lysosomal asparaginyl endopeptidase, legumain was written by Lee, Jiyoun;Bogyo, Matthew. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2012.Synthetic Route of C21H21NO4 The following contents are mentioned in the article:
Legumain or asparaginyl endopeptidase (AEP) is a lysosomal cysteine protease with a high level of specificity for cleavage of protein substrates after an asparagine residue. It is also capable of cleaving after aspartic acids sites when in the acidic environment of the lysosome. Legumain expression and activity is linked to a number of pathol. conditions including cancer, atherosclerosis and inflammation, yet its biol. role in these pathologies is not well-understood. Highly potent and selective inhibitors of legumain would not only be valuable for studying the functional roles of legumain in these conditions, but may have therapeutic potential as well. The authors describe here the design, synthesis and in vitro evaluation of selective legumain inhibitors based on the aza-asparaginyl scaffold. The authors synthesized a library of aza-peptidyl inhibitors with various non-natural amino acids and different electrophilic warheads, and characterized the kinetic properties of inactivation of legumain. The authors also synthesized fluorescently labeled inhibitors to investigate cell permeability and selectivity of the compounds The inhibitors have second order rate constants of up to 5 × 104 M-1 s-1 and IC50 values as low as 4 nM against recombinant mouse legumain. In addition, the inhibitors are highly selective toward legumain and have little or no cross-reactivity with cathepsins. Overall, the authors have identified several valuable new inhibitors of legumain that can be used to study legumain function in multiple disease models. This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5Synthetic Route of C21H21NO4).
(S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5) belongs to piperidine derivatives. Piperidine is a saturated organic heteromonocyclic parent, an azacycloalkane, a secondary amine and a member of piperidines. Fluorinated piperidines are also the subject of continued interest in medicinal chemistry, for example in the synthesis of selective dipeptidyl peptidase II (DPP II) inhibitors. Piperidine derivatives are also used in solid-phase peptide synthesis (SPPS) and many degradation reactions.Synthetic Route of C21H21NO4
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem