Nanoparticles That Display Short Collagen-Related Peptides. Potent Stimulation of Human Platelet Aggregation by Triple Helical Motifs

Collagen plays a key role in the activation and adhesion of blood platelets via their cell-surface receptors. Normally, collagen-related peptides (CRPs), even one as long as a 30-mer (10 Gly-Pro-Hyp (GPO) repeats), are unable to effectively express collagen's platelet-activating behavior. We at...

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Bibliographic Details
Published in:Bioconjugate chemistry 2007-07, Vol.18 (4), p.1025-1027
Main Authors: Cejas, Mabel A, Chen, Cailin, Kinney, William A, Maryanoff, Bruce E
Format: Article
Language:English
Subjects:
Amino Acid Motifs
Biochemistry
Blood
Blood clots
Carrier Proteins - chemistry
Carrier Proteins - pharmacology
Humans
Nanoparticles
Nanoparticles - chemistry
Peptides
Peptides - chemistry
Peptides - pharmacology
Platelet Aggregation - drug effects
Proteins
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Summary:Collagen plays a key role in the activation and adhesion of blood platelets via their cell-surface receptors. Normally, collagen-related peptides (CRPs), even one as long as a 30-mer (10 Gly-Pro-Hyp (GPO) repeats), are unable to effectively express collagen's platelet-activating behavior. We attached two short CRPs, AcHN-(Gly-Pro-Hyp) n Gly-OH with n = 5 (1) and n = 10 (2), via the C-terminus to amino-functionalized latex nanoparticles to create a multimeric display of triple helical motifs. These nanomaterials were characterized by dynamic light scattering and environmental scanning electron microscopy. The nanoparticles bearing the 31-mer CRP sequence, 2, but not the 16-mer sequence, 1, effectively induced the aggregation of human platelets, with a potency level approaching that of native type I collagen. Our results highlight the importance of presenting triple helical CRP motifs of sufficient length on a suitable scaffold in order to stimulate platelets.
ISSN:1043-1802
1520-4812
DOI:10.1021/bc070105s