TY - JOUR
T1 - Syntheses of sulfated glycopolymers and analyses of their BACE-1 inhibitory activity
AU - Nishimura, Yuri
AU - Shudo, Hiroki
AU - Seto, Hirokazu
AU - Hoshino, Yu
AU - Miura, Yoshiko
N1 - Funding Information:
This work was supported by a Grant-in-Aid for Young Scientists (A) ( 23685027 ), and a Grant-in-Aid for Challenging Exploratory Research ( 00335069 ). The computation was primarily carried out using the computer facilities at the Research Institute for Information Technology, Kyushu University.
PY - 2013/12/1
Y1 - 2013/12/1
N2 - The glycopolymers for glycosaminoglycan mimic were synthesized, and the inhibitory effects of Alzheimer's β-secretase (BACE-1) were examined. The regio-selective sulfation was conducted on N-acetyl glucosamine (GlcNAc), and the acrylamide derivatives were synthesized with the consequent sulfated GlcNAc. The glycopolymers were synthesized with acrylamide using radical initiator. The glycopolymer with sulfated GlcNAc showed the strong inhibitory effect on BACE-1, and the inhibitory effects were dependent on the sulfation positions. Especially, glycopolymers carrying 3,4,6-O-sulfo-GlcNAc showed the strong inhibitory effect. The docking simulation suggested that glycopolymers bind to the active site of BACE-1.
AB - The glycopolymers for glycosaminoglycan mimic were synthesized, and the inhibitory effects of Alzheimer's β-secretase (BACE-1) were examined. The regio-selective sulfation was conducted on N-acetyl glucosamine (GlcNAc), and the acrylamide derivatives were synthesized with the consequent sulfated GlcNAc. The glycopolymers were synthesized with acrylamide using radical initiator. The glycopolymer with sulfated GlcNAc showed the strong inhibitory effect on BACE-1, and the inhibitory effects were dependent on the sulfation positions. Especially, glycopolymers carrying 3,4,6-O-sulfo-GlcNAc showed the strong inhibitory effect. The docking simulation suggested that glycopolymers bind to the active site of BACE-1.
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U2 - 10.1016/j.bmcl.2013.09.057
DO - 10.1016/j.bmcl.2013.09.057
M3 - Article
C2 - 24125881
AN - SCOPUS:84886946149
SN - 0960-894X
VL - 23
SP - 6390
EP - 6395
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 23
ER -