Proprotein convertases (PCs) are a family of serine proteases that convert numerous proteins from their initially synthesised non-active precursors into bioactive forms. PCs are hence important regulatory molecules in generating a large number of tissue-specific and functionally important bioactive proteins. These include growth factors, peptide hormones, adhesion molecules, and HIV envelope proteins. PCs are therefore regarded as promising targets for therapeutic applications.
We have discovered that PC6, a member of the PC family, in the uterus is critical for embryo implantation. Preventing PC6 production in the mouse uterus leads to a complete failure of implantation, while blocking PC6 function in human cells inhibits the equivalent critical step of implantation. What makes this discovery more important is that PCs, including PC6, also play a critical role in HIV infection through the activation of HIV envelope proteins. This makes PC6 an exciting target for preventing pregnancy and HIV infection at the same time (a “double whammy” female contraceptive).
We have developed appropriate in vitro model of human embryo implantation, which is suitable for sensitive and high throughput screening for implantation inhibitors. Our research is developing various ways of inhibiting PC6 to prevent embryo implantation in animals and in cell models relevant to human implantation. Our ultimate aim is to develop novel female non-hormonal contraception that could also protect women from HIV infection.
Dr Jian Wang (Shanghai Institute of Planned Parenthood Research, Shanghai, China)
Dr Zhaogui Sun (Shanghai Institute of Planned Parenthood Research, Shanghai, China)
Dr Tracy Nero (St Vincent’s Institute of Medical Research, Melbourne, Australia)
Prof Michael Parker (St Vincent’s Institute of Medical Research, Melbourne, Australia)
Dr Guan-Sheng Jiao (PanThera Biopharma LLC, Hawaii, USA)