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Inhibition of plasma-mediated adherence of sickle erythrocytes to microvascular endothelium by conformationally constrained RGD-containing peptides.
Am J Hematol. 1996 Oct; 53(2):92-8.AJ

Abstract

Adherence of sickle erythrocytes to vascular endothelium likely initiates or participates in microvascular occlusion, leading to ischemic tissue and organ damage characteristic of sickle-cell pain episodes. In vitro, sickle-cell adherence to endothelium involves adhesive plasma proteins and integrin and nonintegrin receptors on sickle cells and endothelial cells. The involvement of arginine-glycine-aspartic acid (RGD) sequences in adhesive plasma proteins and integrin receptors suggests that RGD-containing peptides may inhibit sickle-cell/endothelial-cell adherence. In the present study, inhibition of plasma-mediated sickle-erythrocyte adherence to endothelium using conformationally constrained RGD-containing peptides was quantified in vitro under continuous flow at a shear stress of 1.0 dyn/cm2. Two conformationally constrained RGD peptides were investigated: 6Z (which has high affinity for alpha5beta1, alpha(V)beta3, and alpha(IIIb)beta3 integrin receptors), and TP9201 (which preferentially binds to alpha(IIb)beta3). Peptide 6Z at 50 microM inhibited plasma-mediated sickle-cell adherence to microvascular endothelium 70% when incubated with sickle red cells, and 63% when incubated with endothelium. Under similar conditions, peptide TP9201 inhibited plasma-mediated sickle-cell adherence up to 85% at concentrations from 250 to 500 microM TP9201. The inhibition of plasma-mediated adherence by conformationally constrained RGD peptides, but not by linear or circular constructs, suggests that the tertiary structure of the peptide containing the binding sequence is important. Inhibition of plasma-mediated sickle-cell adhesion with these peptides in vitro suggests that such conformationally constrained RGD peptides could provide therapeutic interventions in the course of the disease by inhibiting receptor-ligand interactions.

Authors+Show Affiliations

School of Chemical Engineering, Georgia Institute of Technology Atlanta 30332-0100, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

8892733

Citation

Kumar, A, et al. "Inhibition of Plasma-mediated Adherence of Sickle Erythrocytes to Microvascular Endothelium By Conformationally Constrained RGD-containing Peptides." American Journal of Hematology, vol. 53, no. 2, 1996, pp. 92-8.
Kumar A, Eckman JR, Wick TM. Inhibition of plasma-mediated adherence of sickle erythrocytes to microvascular endothelium by conformationally constrained RGD-containing peptides. Am J Hematol. 1996;53(2):92-8.
Kumar, A., Eckman, J. R., & Wick, T. M. (1996). Inhibition of plasma-mediated adherence of sickle erythrocytes to microvascular endothelium by conformationally constrained RGD-containing peptides. American Journal of Hematology, 53(2), 92-8.
Kumar A, Eckman JR, Wick TM. Inhibition of Plasma-mediated Adherence of Sickle Erythrocytes to Microvascular Endothelium By Conformationally Constrained RGD-containing Peptides. Am J Hematol. 1996;53(2):92-8. PubMed PMID: 8892733.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of plasma-mediated adherence of sickle erythrocytes to microvascular endothelium by conformationally constrained RGD-containing peptides. AU - Kumar,A, AU - Eckman,J R, AU - Wick,T M, PY - 1996/10/1/pubmed PY - 2000/6/20/medline PY - 1996/10/1/entrez SP - 92 EP - 8 JF - American journal of hematology JO - Am J Hematol VL - 53 IS - 2 N2 - Adherence of sickle erythrocytes to vascular endothelium likely initiates or participates in microvascular occlusion, leading to ischemic tissue and organ damage characteristic of sickle-cell pain episodes. In vitro, sickle-cell adherence to endothelium involves adhesive plasma proteins and integrin and nonintegrin receptors on sickle cells and endothelial cells. The involvement of arginine-glycine-aspartic acid (RGD) sequences in adhesive plasma proteins and integrin receptors suggests that RGD-containing peptides may inhibit sickle-cell/endothelial-cell adherence. In the present study, inhibition of plasma-mediated sickle-erythrocyte adherence to endothelium using conformationally constrained RGD-containing peptides was quantified in vitro under continuous flow at a shear stress of 1.0 dyn/cm2. Two conformationally constrained RGD peptides were investigated: 6Z (which has high affinity for alpha5beta1, alpha(V)beta3, and alpha(IIIb)beta3 integrin receptors), and TP9201 (which preferentially binds to alpha(IIb)beta3). Peptide 6Z at 50 microM inhibited plasma-mediated sickle-cell adherence to microvascular endothelium 70% when incubated with sickle red cells, and 63% when incubated with endothelium. Under similar conditions, peptide TP9201 inhibited plasma-mediated sickle-cell adherence up to 85% at concentrations from 250 to 500 microM TP9201. The inhibition of plasma-mediated adherence by conformationally constrained RGD peptides, but not by linear or circular constructs, suggests that the tertiary structure of the peptide containing the binding sequence is important. Inhibition of plasma-mediated sickle-cell adhesion with these peptides in vitro suggests that such conformationally constrained RGD peptides could provide therapeutic interventions in the course of the disease by inhibiting receptor-ligand interactions. SN - 0361-8609 UR - https://www.unboundmedicine.com/medline/citation/8892733/Inhibition_of_plasma_mediated_adherence_of_sickle_erythrocytes_to_microvascular_endothelium_by_conformationally_constrained_RGD_containing_peptides_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0361-8609&date=1996&volume=53&issue=2&spage=92 DB - PRIME DP - Unbound Medicine ER -