본문 바로가기
HOME> 논문 > 논문 검색상세

논문 상세정보

Higher-affinity oligosaccharide ligands for E-selectin.

Nelson, R M Dolich, S Aruffo, A Cecconi, O Bevilacqua, M P
  • 초록  

    A series of synthetic oligosaccharides based on sialyl Lewis x (sLex; Neu5Ac alpha 2-3Gal beta 1-4[Fuc alpha 1-3]GlcNAc) and sialyl Lewis a (sLea; Neu5Ac alpha 2-3Gal beta 1-3[Fuc alpha 1-4]GlcNAc) was used to study the binding interactions of selectins. E-selectin-immunoglobulin fusion protein (E-selectin-Ig) bound to immobilized bovine serum albumin (BSA)-neoglycoproteins containing sLex or sLea in a Ca(2+)-dependent manner. Solution-phase sLex tetrasaccharide blocked this interaction by 50% at a concentration of 750 +/- 20 microM (IC50). sLea was more effective (IC50 = 220 +/- 20 microM), while nonsialylated, nonfucosylated derivatives showed little or no activity at concentrations up to 1 mM. Attachment of an 8-methoxycarbonyloctyl aglycone in a beta linkage to the anomeric carbon of the GlcNAc of sLex or sLea increased their blocking activity nearly twofold. Finally, replacement of the 2-N-acetyl substituent of the GlcNAc by an azido or amino group resulted in substantial increases in activity, with the most potent inhibitor being amino substituted sLea, which was 36-fold more active (IC50 = 21 +/- 3 microM) than the reducing tetrasaccharide sLex. In contrast to results obtained with E-selectin-Ig, P-selectin-Ig binding to immobilized BSA-sLea was blocked modestly by most oligosaccharides at 1 mM, with no substantial differences among them. IC50 values of soluble oligosaccharides determined in competitive binding studies accurately predicted blocking of leukocyte adhesion to recombinant E-selectin-Ig and to cytokine-activated endothelium.


  • 원문보기

    원문보기
    무료다운로드 유료다운로드
    • 원문이 없습니다.

    유료 다운로드의 경우 해당 사이트의 정책에 따라 신규 회원가입, 로그인, 유료 구매 등이 필요할 수 있습니다. 해당 사이트에서 발생하는 귀하의 모든 정보활동은 NDSL의 서비스 정책과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니 담기를 통하여 원문복사서비스 이용이 가능합니다.

 활용도 분석

  • 상세보기

    amChart 영역
  • 원문보기

    amChart 영역