P-selectin blocking potency of multimeric tyrosine sulfates in vitro and in vivo.
P-selectin blocking potency was investigated using synthetic monomeric and polymeric anionic compounds containing sulfate groups such as O-sulfotyrosine (sTyr) and/or sulfated Lewis structures. A non-carbohydrate-containing polyacrylamide conjugate sTyr-PAA (80% mol of sTyr) was a remarkably potent inhibitor of P-selectin binding in vitro, having an IC(50) value of 6 ng/mL (equivalent to 10 nM calculated on the basis of sTyr residues or 0.1 nM calculated by the mass of the macromolecule). The inhibitory effect of sTyr-PAA (80%) towards P-selectin is significantly greater than that of fucoidan (IC(50), 100 ng/mL). However, sTyr-PAA (80%) was less effective than fucoidan at reducing neutrophil extravasation in an in vivo rat model of peritonitis.
Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16/10, 117997 Moscow, Russia.
Tatyana V
TV
Pochechueva
Natalia A
NA
Ushakova
Marina E
ME
Preobrazhenskaya
Nikolay E
NE
Nifantiev
Yu E
YE
Tsvetkov
Marina A
MA
Sablina
Alexander B
AB
Tuzikov
Mike I
MI
Bird
Robert
R
Rieben
Nicolai V
NV
Bovin
D000180:Acrylic Resins / Q000737:chemistry; D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D019281:Dimerization; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D016256:Lewis X Antigen / Q000737:chemistry / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects; D019007:P-Selectin / Q000187:drug effects* / Q000378:metabolism; D010538:Peritonitis / Q000188:drug therapy; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D000099166:Polyacrylamides
D000180:Acrylic Resins; D016256:Lewis X Antigen; D019007:P-Selectin; D014443:Tyrosine; D000099166:Polyacrylamides; C005662:tyrosine O-sulfate