Cross-linking exogenous bifunctional peptides into fibrin gels with factor XIIIa

Jason C. Schense, Jeffrey A. Hubbell

Research output: Contribution to journalArticle

239 Citations (Scopus)

Abstract

Bi-domain peptides with a factor XIIIa substrate in one domain and a bioactive peptide in another domain were covalently incorporated into fibrin gels during coagulation through the action of the transglutaminase factor XIIIa. The cross-linking characteristics were determined for two bi-domain peptides with factor XIIIa substrates based on fibrinogen, dYRGDTIGEGQQHHLGG-NH2, and dLRGDGAKDV-NH2, as well as one bi-domain peptide with a substrate sequence based on α2-plasmin inhibitor, dLNQEQVSPLRGD-NH2, and another with a nonbiological, oligolysine substrate, dLRGDKKKKG-NH2 (substrate domains in italic). Each of these peptides was able to cross-link into the fibrin gels during coagulation, with the peptide containing the factor XIIIa substrate based on α2-plasmin inhibitor being incorporated at levels in excess of 8 mol/mol fibrinogen. The structural characteristics of these peptide-modified gels proved to be the same as those for a native fibrin gel. The bioactivity of the incorporated active factors was tested in a neuronal culture model with day 8 chicken dorsal root ganglia using two bioactive sequences, RGD and DGEA, and one inactive control sequence, RDG. Each of these peptides influenced the extension of neurites from the ganglia as expected, indicating that the incorporated factors retained their activity. With the use of soluble competitive inhibitors, it was shown that this effect was due to the covalently incorporated peptides. Through exploiting the role of factor XIIIa in coagulation, we have developed a method by which to impart the character of nonfibrin proteins, such as extracellular matrix proteins, to fibrin, a biological material with many potential therapeutic and academic applications.

Original languageEnglish
Pages (from-to)75-81
Number of pages7
JournalBioconjugate Chemistry
Volume10
Issue number1
DOIs
StatePublished - Jan 1 1999
Externally publishedYes

Fingerprint

Factor XIIIa
Fibrin
Peptides
Gels
Antifibrinolytic Agents
Substrates
Coagulation
Fibrinogen
Transglutaminases
Extracellular Matrix Proteins
Spinal Ganglia
Neurites
Ganglia
Proteins
Chickens
Bioactivity
Biological materials
Protein Domains

ASJC Scopus subject areas

  • Chemistry(all)
  • Organic Chemistry
  • Clinical Biochemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry

Cite this

Cross-linking exogenous bifunctional peptides into fibrin gels with factor XIIIa. / Schense, Jason C.; Hubbell, Jeffrey A.

In: Bioconjugate Chemistry, Vol. 10, No. 1, 01.01.1999, p. 75-81.

Research output: Contribution to journalArticle

Schense, Jason C. ; Hubbell, Jeffrey A. / Cross-linking exogenous bifunctional peptides into fibrin gels with factor XIIIa. In: Bioconjugate Chemistry. 1999 ; Vol. 10, No. 1. pp. 75-81.
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