Multivalent HSA conjugates of 3'-sialyllactose are potent inhibitors of adenoviral cell attachment and infection.
Adenoviruses of serotypes 8, 19 and 37 are the major cause of the severe eye infection EKC (epidemic keratoconjunctivitis). In general, all adenoviruses interact with their cellular receptors through the fibre proteins, which extend from the virus particle. Recently, adenovirus type 37 (Ad37) was found to bind and infect human corneal cells through attachment to carbohydrate structures that carry terminal alpha-(2-3)-linked sialic acids. Herein we present a synthetic route to a 3'-sialyllactose derivative and corresponding multivalent HSA conjugates with varying orders of valency. The potential of these compounds as inhibitors of EKC-causing adenovirus of serotype Ad37, was studied with both a binding assay and an infectivity assay. The results revealed that these compounds effectively prevent Ad37 from binding to and infecting human corneal epithelial (HCE) cells. Moreover, the inhibition is significantly increased with higher orders of multivalency.
Johansson
Susanne M C
SM
Organic Chemistry, Department of Chemistry, Umeå Universitet, 901 87 Umeå, Sweden.
Arnberg
Niklas
N
Elofsson
Mikael
M
Wadell
Göran
G
Kihlberg
Jan
J
D000256:Adenoviridae / Q000378:metabolism* / Q000472:pathogenicity; D000258:Adenovirus Infections, Human; D000818:Animals; D002460:Cell Line; D006801:Humans; D007637:Keratoconjunctivitis / Q000821:virology; D015394:Molecular Structure; D009844:Oligosaccharides / Q000737:chemistry* / Q000378:metabolism*; D011991:Receptors, Virus / Q000737:chemistry / Q000378:metabolism; D012709:Serum Albumin / Q000737:chemistry*
C421467:3'-sialyllactose; D009844:Oligosaccharides; D011991:Receptors, Virus; D012709:Serum Albumin