Novel azapeptide inhibitors of cathepsins B and K. Structural background to increased specificity for cathepsin B

Abstract: We have designed and synthesized a new series of azapeptides which act as potential inhibitors of cathepsin B and/or cathepsin K. Their structures are based upon the inhibitory sites of natural cysteine protease inhibitors, cystatins. For the synthesized azapeptides, the equilibrium constants for dissociation of inhibitor–enzyme complex, K_i, were determined. Comparison of these values indicated that all of the azainhibitors act much stronger toward cathepsin B. Z‐Arg‐Leu‐His‐Agly‐Ile‐Val‐OMe ( 7 ) proved to be approximately 500 times more potent for cathepsin B than for cathepsin K. To be able to explain the obtained experimental values we used the molecular dynamics procedures to analyze the interactions between cathepsin B and compound 7 . We also determined the structure of the most potent and selective cathepsin B azainhibitor by means of NMR studies and theoretical calculations. In this report, we describe SAR studies of azapeptide inhibitors indicating the influence of the conformational flexibility of the examined compounds on inhibition of cathepsins B and K.     

Alice in Wonderland syndrome as a presenting symptom of EBV infection

Four Chinese patients (2 boys, 2 girls), ages 4–9 years, who had episodes of perception error of body schema and objects are reported. The metamorphopsia, which had been named Alice in Wonderland syndrome, is the major presentation. All of them were proved to have acute Epstein-Barr virus infection, as documented by positive heterophil antibody test and/or positive IgM antibody to Epstein-Barr virus capsid antigen. The duration of the perception disorder ranged from 1 week to 3 months. We believe that any young child presenting with Alice in Wonderland syndrome should undergo examination for Epstein-Barr virus infection; complete recovery from the disorder can be expected.     

The red eye

A red eye is a cardinal sign of ocular inflammation. Most cases are benign and can be managed by the primary care provider. The key is recognizing cases requiring ophthalmological consultation by differentiating between ciliary and conjunctival injection. Ciliary injection indicates inflammation of the cornea, iris, or ciliary body, whereas conjunctival injection mainly affects the posterior conjunctival blood vessels. The author has stated that he does not have a significant financial interest or other relationship with any product manufacturer or provider of services discussed in this article. The author also does not discuss the use of off-label products, which includes unlabeled, unapproved, or investigative products or devices.