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 attached two short CRPs, AcHN-(Gly-Pro-Hyp)nGly-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.
Cejas
Mabel A
MA
Vascular Research Team, Johnson & Johnson Pharmaceutical Research and Development, Spring House, Pennsylvania 19477-0776, USA.
Chen
Cailin
C
Kinney
William A
WA
Maryanoff
Bruce E
BE
D020816:Amino Acid Motifs; D002352:Carrier Proteins / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*
D002352:Carrier Proteins; D010455:Peptides; C435908:collagen-related peptide