title: 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.
authors.affiliation: Department of Pharmacy, Rheinische Friedrich Wilhelms University Bonn, Av. der Immenburg 4, 531L1 Bonn, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Simonis
authors.forename: Katrin
authors.initials: K
authors.lastname: Christ
authors.forename: Susanne
authors.initials: S
authors.lastname: Alban
authors.forename: Gerd
authors.initials: G
authors.lastname: Bendas
mesh_terms: D000925:Anticoagulants / Q000737:chemistry* / Q000627:therapeutic use; D017984:Enoxaparin / Q000737:chemistry* / Q000627:therapeutic use; D006801:Humans; D007700:Kinetics; D019041:L-Selectin / Q000737:chemistry* / Q000378:metabolism; D017762:Nadroparin / Q000737:chemistry* / Q000627:therapeutic use; D009362:Neoplasm Metastasis / Q000188:drug therapy; D019007:P-Selectin / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin; D017762:Nadroparin; D019007:P-Selectin; D011993:Recombinant Fusion Proteins; D019041:L-Selectin