Synthesis ofN-acetyl Glucosamine Analogs as Inhibitors for Hyaluronan Biosynthesis.
Elevated hyaluronan expression is a hallmark of many types of cancer. Therefore, inhibition of hyaluronan biosynthesis can potentially slow the growth of tumor cells. Herein, we explore a chain termination strategy to reduce hyaluronan synthesis by tumor cells. Several analogs of glucosamine were prepared, which contained modifications at the C-3 positions. These analogs can possibly cap the nonreducing end of a growing hyaluronan chain, thus lowering the amount of hyaluronan synthesized. Upon incubation with pancreatic cancer cells, a fluorine-containing glucosamine analog was found to exhibit significant inhibitory activities of hyaluronan synthesis. Furthermore, it drastically reduced the proliferation of cancer cells.
Department of Chemistry, Michigan State University, East Lansing, MI 48824, USA.
Gilbert
G
Wasonga
Department of Glycotechnology, Center for Advanced Medical Research, Hirosaki University Graduate School of Medicine, Hirosaki 036-8224, Japan.
Yota
Y
Tatara
Department of Glycotechnology, Center for Advanced Medical Research, Hirosaki University Graduate School of Medicine, Hirosaki 036-8224, Japan.
Ikuko
I
Kakizaki
Department of Chemistry, Michigan State University, East Lansing, MI 48824, USA.
Xuefei
X
Huang
Biosynthesis; Chain terminator; Hyaluronan; Inhibitor; Salvage pathway