561007-53-2Relevant academic research and scientific papers
Phosphinotripeptidic inhibitors of leucylaminopeptidases
Jewgiński, Micha?,Haremza, Kinga,de los Santos, Jesús M.,Sbai, Zouhair Es,Oszywa, Bartosz,Pawe?czak, Ma?gorzata,Palacios, Francisco,Latajka, Rafa?
, (2021/05/19)
Phosphinate pseudopeptide are analogs of peptides containing phosphinate moiety in a place of the amide bond. Due to this, the organophosphorus fragment resembles the tetrahedral transition state of the amide bond hydrolysis. Additionally, it is also capable of coordinating metal ions, for example, zinc or magnesium ions. These two properties of phosphinate pseudopeptides make them an ideal candidate for metal-related protease inhibitors. This research investigates the influence of additional residue in the P2 position on the inhibitory properties of phosphinopeptides. The synthetic strategy is proposed, based on retrosynthetic analysis. The N-C-P bond formation in the desired compounds is conveniently available from the three-component condensation of appropriate amino components, aldehydes, and hypophosphorous acid. One of the crucial synthetic steps is the careful selection of the protecting groups for all the functionals. Determination of the inhibitor activity of the obtained compounds has been done using UV-Vis spectroscopy and standard substrate L-Leu-p-nitroanilide toward the enzymes isolated from the porcine kidney (SsLAP, Sus scrofa Leucine aminopeptidase) and barley seeds (HvLAP, Hordeum vulgare Leucine aminopeptidase). An efficient procedure for the preparation of phosphinotripeptides has been performed. Activity test shown that introduction of additional residue into P2 position obtains the micromolar range inhibitors of SsLAP and HvLAP. Moreover, careful selection of the residue in the P2 position should improve its selectivity toward mammalian and plant leucyl aminopeptidases.
Specific interactions of divalent metal ions with phosphonic analogues of dipeptide inhibitors of proteases
Galezowska,Sobek,Drag,Mucha,Kafarski,Kozlowski
, p. 603 - 617 (2007/10/03)
Potentiometric and spectroscopic methods were used to evaluate the binding ability of two dipetides with C-terminal phosphonic group. This phopshonate moiety is quite effective in the coordination of metal ions. The two phosphinate analogues, which are ve
Synthesis and activity of phosphinic tripeptide inhibitors of cathepsin C
Mucha, Artur,Pawelczak, Malgorzata,Hurek, Jozef,Kafarski, Pawel
, p. 3113 - 3116 (2007/10/03)
Phosphinic tripeptide analogues Gly-Xaaψ[P(O)(OH)CH2]-Gly have been developed as inhibitors of cathepsin C (DPP I), a lysosomal, papain-like cysteine protease. The target compounds were synthesised by addition of methyl acrylate to the appropri
The most potent organophosphorus inhibitors of leucine aminopeptidase. Structure-based design, chemistry, and activity
Grembecka, Jolanta,Mucha, Artur,Cierpicki, Tomasz,Kafarski, Pawe?
, p. 2641 - 2655 (2007/10/03)
A new class of very potent inhibitors of cytosol leucine aminopeptidase (LAP), a member of the metalloprotease family, is described. The X-ray structure of bovine lens leucine aminopeptidase complexed with the phosphonic acid analogue of leucine (LeuP) wa
