My research is mainly devoted to further improvement of leptin antagonists by increasing their affinity toward the receptor and extending their in vivo persistence in circulation and subsequently testing them in various conditions in vitro and in vivo. Increase in affinity is achieved by using error-prone PCR, creating a large library of mutants and selecting of high affinity mutants by yeast surface display method. So far we have identified 6 mutants with affinity increased 10 – 50 fold. To extend in vivo half life we have developed a protocol of mono-pegylation of leptin or leptin antagonists. Pegylated leptin antagonists have a profound reversible weight gaining effect in mice whereas pegylated leptin leads to weight loss. Leptin antagonists are tested for their anti-inflammatory activity in various mice models of autoimmune diseases in collaboration of researchers (Dr. E. Elinav and Prof. Z. Halpern) from Ichilov Hospital and this project was patented and licensed for development into a medicine to BiolineRX by Yissum. In additional projects in collaboration with researchers from Agricultural Research Organization we investigate the functional aspects of polymorphism in ruminants (Dr. E. Gotwine) and prepare analogs of phospholipase A2 as possible anti-mastitis agents (Dr. E. Sarusi). In a new project starting in Dec 2008 we investigate the effect of ruminant leptin antagonists to increase appetite and adaptive metabolism in ruminants in collaboration with Prof. Y.R. Boisclair from Cornell University.
- Development of high affinity leptin antagonists
- Development and bioactivity of pegylated leptin antagonists
- Functional aspects of polymorphism in ruminants
- Preparation of recombinant PLA2 as an anti-mastitis reagent
- Use of leptin antagonists to increase appetite and adaptive metabolism in ruminants