Design och syntes av potentiella inhibitorer för galektin-1

Sammanfattning: Galectin-1 is a member of the carbohydrate-binding protein family galectins. Galectins are involved in the immune system. However, in cancer growth, galectin-1 is overproduced to not make the immune system respond. Therefore, inhibitors of the protein were synthesized to make the immune system approach the cancer and respond. From previous studies and simulations on the computer program Maestro different inhibitors were designed to target tumor growth in the brain going through the blood-brain barrier. A difficulty was to design a molecule nonpolar enough to go through the barrier but still be soluble in the body. The common parts of the inhibitors were a triazole, thiophen, hydroxyl group toward the inner part of the binding site. The otherward part were different in form of variation of rings and functional groups trying to target different and specific aminoamides selective to galectin-1. The majority of the synthesized compounds were not bindning to galectin-3 but were all binding to galectin-1, except one. The most promising compounds were VU33 and VU21. The sidechain of VU33 was composed of one five-ring with two nitrogen’s and one benzene ring. According to modelling, the sidechain interacted well with Glu71 and Trp68 which probably is the reason for the good affinity. The sidechain of VU21 was partially composed of coumarin with a carbonyl carbon directed towards the end of the molecule which according to modelling interacted well with Glu71. To conclude, the study was a success in the means of synthesizing inhibitors for galectin-1 and concluding character trades for better and worse inhibitors.