Article

Abstract

• Blood coagulation involves activation of platelets and coagulation factors. At the interface of these two processes resides the lipid phosphatidylserine. Activated platelets expose phosphatidylserine on their outer membrane leaflet and activated clotting factors assemble into enzymatically active complexes on the exposed lipid, ultimately leading to the formation of fibrin. Here, we describe how small peptide and peptidomimetic probes derived from the lipid binding domain of the protein myristoylated alanine-rich C-kinase substrate (MARCKS) bind to phosphatidylserine exposed on activated platelets and thereby inhibit fibrin formation. The MARCKS peptides antagonize the binding of factor Xa to phosphatidylserine and inhibit the enzymatic activity of prothrombinase. In whole blood under flow, the MARCKS peptides colocalize with, and inhibit fibrin cross-linking, of adherent platelets. In vivo, we find that the MARCKS peptides circulate to remote injuries and bind to activated platelets in the inner core of developing thrombi.

Creator

• Brodsky, Gary L
• Yin, Hang
• Onasoga, Abimbola
• White, Ormacinda R
• Paola, Jorge Di
• Brown, Peter N
• Brass, Lawrence F
• Branchford, Brian R
• Kastelowitz, Noah
• Tamura, Ryo
• Stalker, Timothy J

Date Issued

• 2017-06-27

Academic Affiliation

• Chemical and Biological Engineering

Journal Title

• Scientific Reports

Journal Issue/Number

• 1

Journal Volume

• 7

File Extent

• 4275-4275

Last Modified

• 2019-12-05

Identifier

• PubMed ID: 28655899

Resource Type

• Article

Rights Statement

• In Copyright

DOI

•  https://doi.org/10.1038/s41598-017-04494-y

ISSN

• 2045-2322

Language

• English [eng]

License

• Creative Commons BY Attribution 4.0 International

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