Synthesis of selective inhibitors against V. cholerae sialidase and human cytosolic sialidase NEU2.
Sialidases or neuraminidases catalyze the hydrolysis of terminal sialic acid residues from sialyl oligosaccharides and glycoconjugates. Despite successes in developing potent inhibitors specifically against influenza virus neuraminidases, the progress in designing and synthesizing selective inhibitors against bacterial and human sialidases has been slow. Guided by sialidase substrate specificity studies and sialidase crystal structural analysis, a number of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (DANA or Neu5Ac2en) analogues with modifications at C9 or at both C5 and C9 were synthesized. Inhibition studies of various bacterial sialidases and human cytosolic sialidase NEU2 revealed that Neu5Gc9N(3)2en and Neu5AcN(3)9N(3)2en are selective inhibitors against V. cholerae sialidase and human NEU2, respectively.
Department of Chemistry, University of California, One Shields Avenue, Davis, California 95616, USA.
Zahra
Z
Khedri
Yanhong
Y
Li
Hongzhi
H
Cao
Jingyao
J
Qu
Hai
H
Yu
Musleh M
MM
Muthana
Xi
X
Chen
D060326:Chemistry Techniques, Synthetic; D003600:Cytosol / Q000201:enzymology*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D009438:Neuraminic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D011487:Protein Conformation; D014734:Vibrio cholerae / Q000201:enzymology*
D004791:Enzyme Inhibitors; D009438:Neuraminic Acids; C403285:NEU2 protein, human; D009439:Neuraminidase