Glycoprotein Ibα peptides inhibit thrombin and SFLLRN-induced platelet aggregation

The platelet glycoprotein Ib(alpha) (GPIb(alpha)) receptor contains a high-affinity binding site for thrombin that, when occupied, augments platelet activation and aggregation in part via the 7-transmembrane domain receptor (7-TMDR). We have constructed a series of peptides derived from GPIb(alpha)...

Full description

Saved in:

Bibliographic Details
Published in:	The Journal of laboratory and clinical medicine Vol. 128; no. 5; pp. 492 - 495
Main Authors:	MQCKEOWN, L. P, WILLIAMS, S. B, HANSMANN, K. E, KRUTZSCH, H, GRALINICK, H. R
Format:	Journal Article
Language:	English
Published:	Saint Louis, MO Elsevier 01-11-1996
Subjects:	Amino Acid Sequence Biological and medical sciences Blood coagulation. Blood cells Fundamental and applied biological sciences. Psychology Humans In Vitro Techniques Molecular and cellular biology Molecular Sequence Data Oligopeptides - chemistry Oligopeptides - pharmacology Peptide Fragments - antagonists & inhibitors Peptide Fragments - chemistry Peptide Fragments - genetics Peptide Fragments - pharmacology Platelet Platelet Aggregation - drug effects Platelet Glycoprotein GPIb-IX Complex - chemistry Platelet Glycoprotein GPIb-IX Complex - genetics Platelet Glycoprotein GPIb-IX Complex - pharmacology Receptors, Thrombin - chemistry Receptors, Thrombin - genetics Structure-Activity Relationship Thrombin - antagonists & inhibitors Thrombin - pharmacology Aggregation Human Platelet Thrombin(drug) Coagulation Activation Glycoproteins
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	The platelet glycoprotein Ib(alpha) (GPIb(alpha)) receptor contains a high-affinity binding site for thrombin that, when occupied, augments platelet activation and aggregation in part via the 7-transmembrane domain receptor (7-TMDR). We have constructed a series of peptides derived from GPIb(alpha) that encompass the amino acid sequence F216-T240. We have studied the effect(s) of these peptides on platelet aggregation induced by thrombin or by the 7-TMDR peptide SFLLRN. Twenty-four peptides were synthesized from the peptide sequence F216-T240. Several of the peptides derived from the sequence W219-V227 of GPIb(alpha) inhibited platelet aggregation, which was primarily dependent on the presence of the amino acid sequence A224-N226 (AEN). These data suggest that a region within the GPIb(alpha) chain modulates the platelet aggregation induced by alpha-thrombin. These GPIb(alpha) peptides did not interfere with platelet aggregation induced by other agonists--for example, collagen, ristocetin, calcium ionophore, or botrocetin--which indicates that these GPIb(alpha) peptide-platelet interaction(s) are specific. Our studies provide another potential mechanism for modulating platelet activation and aggregation via synthetic and natural peptides.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0022-2143 1532-6543
DOI:	10.1016/S0022-2143(96)90046-3