Affinity and Kinetics of Different Heparins Binding to P- and L-Selectin

Abstract

Selectins are adhesion receptors that participate in inflammation and tumor cell metastasis. The anti-inflammatory and antimetastatic activities of heparins have been related partly to their ability to interact with P- and L-selectin. The recent findings that various heparins differ in antimetastatic activity were explained by differences in their P- and L-selectin binding ability. To obtain data to illustrate the binding characteristics, we detected for the first time the binding kinetics and affinity of the two low molecular weight heparins (LMWHs) enoxaparin and nadroparin, and of the unfractionated heparin Liquemin N to P- and L-selectin using a quartz crystal microbalance biosensor. Enoxaparin and nadroparin behave nearly identical in their binding affinity to both P-selectin ( KD 4.60 x 10 (- 6) M versus 7.61 x 10 (- 6) M) and L-selectin ( KD 2.01 x 10 (- 6) M versus 2.84 x 10 (- 6) M). Liquemin N displayed slightly higher affinities to both selectins ( KD 6.07 x 10 (- 7) M versus 1.07 x 10 (- 7) M). The differences are caused by a higher association rate compared with that of the LMWHs. These data support recent findings of antimetastatic activities, but illustrate that the intrinsic selectin binding does not entirely reflect the antimetastatic activities in vivo.

Dynamic Interaction of the Measles Virus Hemagglutinin with Its Receptor Signaling Lymphocytic Activation Molecule (SLAM, CD150)

“…Based on SPR binding analysis, Hashiguchi et al (2007) reported that the wild-type strain (IC-B) H-protein does not bind to CD46. We tested the binding kinetics of sH ICB carrying the N481Y mutation and recorded a K d of 1460 nM, an affinity similar to that seen between cell adhesion molecules (34). Thus, the single Tyr substitution at 481 confers on the H-protein the ability to bind CD46, where previously it had no interaction.…”

Structural Variations of the Cell Wall Precursor Lipid II and Their Influence on Binding and Activity of the Lipoglycopeptide Antibiotic Oritavancin

“…To further validate the data obtained from the in vitro assays, the binding parameters of oritavancin and vancomycin to selected lipid II variants (lipid II, lipid II-Gly 5 , amidated lipid II, amidated lipid II-Gly 5 , lipid II-D-Lac, and amidated lipid II-D-Lac) were determined using a quartz crystal microbalance (QCM) technique (48)(49)(50).…”

“…After equilibration of the quartz crystals under flow conditions until they reached a constant frequency, 1 M peptide solution was added. The frequency curves allow the calculation of the kinetic binding constants as described previously (49,50).…”

The Role of Dimension in Multivalent Binding Events: Structure–Activity Relationship of Dendritic Polyglycerol Sulfate Binding to L‐Selectin in Correlation with Size and Surface Charge Density

“…[18] Among this class of inhibitors is heparin, a naturally occurring polysaccharide isolated from animal tissue, which shows moderate anti-inflammatory potential in addition to a strong anti-coagulant effect. [19] This limits the extensive use of heparin in anti-inflammatory therapy due to the related risk of bleeding. However, heparinoids with reduced or no anti-coagulant properties but remaining selectin affinity have been developed.…”