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This paper focuses on the inhibitory mechanism of E-64 and its derivatives (epoxysuccinyl-based inhibitors) with some cysteine proteases, based on the binding modes observed in the x-ray crystal structures of their enzyme-inhibitor complexes. E-64 is a potent irreversible inhibitor against general cysteine proteases, and its binding modes with papain, actinidin, cathepsin L, and cathepsin K have been reviewed at the atomic level. E-64 interacts with the Sn subsites of cysteine proteases. Although the Sn-Pn (n = 1-3) interactions of the inhibitor with the main chains of the active site residues are similar in respective complexes, the significant difference is observed in the side-chain interactions of S2-P2 and S3-P3 pairs because of different residues constituting the respective subsites. E-64-c and CA074 are representative derivatives developed from E-64 as a clinical usable and a cathepsin B-specific inhibitors, respectively. In contrast with similar binding/inhibitory modes of E-64-c and E-64 for cysteine proteases, the inhibitory mechanism of cathepsin B-specific CA074 results from the binding to the Sn' subsite.

Background Despite the non-invasive nature of non-invasive prenatal testing (NIPT), there is still a need for a separate informed consent process before testing. The objectives of this study are to assess (a) knowledge and preferences of Chinese women in a major public hospital in Hong Kong who underwent NIPT, and (b) whether their knowledge and preferences differ depending on womens’ characteristics and sources of information. Methods Setting: prenatal diagnosis and counselling clinic. Between February 2012 and September 2013, a questionnaire survey was distributed to all women who underwent NIPT after positive aneuploidy screening. As a pilot study, ten knowledge questions were designed based on the rapid response statement on Prenatal Detection of Down Syndrome using Massively Parallel Sequencing from the International Society for Prenatal Diagnosis in 2011. The source of women’s knowledge and their preferences were also evaluated. While conventional screening was publicly funded, NIPT was not. Differences between subgroups were compared using chi square tests and logistic regression analysis. Results Of 152 women who underwent NIPT, 135 (88.8 %) completed their questionnaires. More than 90 % of women recognised the possibility of false positive and false negative results. Slightly more than 70 % of women knew the inferior sensitivity of NIPT compared to an invasive test, and the possibility of an uninformative test result, but were not aware of the complicated aspects of NIPT. Pregnant women with an advanced level of education or those who underwent NIPT before 15 weeks provided answers that was more accurate by around 10-20 % in two to three knowledge questions than those without. These associations were confirmed by multivariate logistic regression analysis. The women received information on NIPT largely from their private doctors (47.4 %) and web (41.5 %). In their future pregnancies, more women would opt for NIPT (a self-financed item) after positive screening (‘free’ in a public hospital) (57.8 %) than as a primary screening (30.4 %). Conclusions It is feasible to use a questionnaire based on the ISPD statement on NIPT to assess women’s knowledge of the test. The Chinese women who underwent NIPT recognised the limitations, but did not understand the complicated aspects. More information should be provided by health care professionals in order to facilitate an informed choice by patients. More women preferred NIPT as a contingent test than as a primary screening probably because of its high cost.