A novel class of small functional peptides that bind and inhibit human alpha-thrombin isolated by mRNA display

Chem Biol. 2003 Jan;10(1):69-79. doi: 10.1016/s1074-5521(02)00309-5.

Abstract

Here we report the in vitro selection of novel small peptide motifs that bind to human alpha-thrombin. We have applied mRNA display to select for thrombin binding peptides from an unbiased library of 1.2 x 10(11) different 35-mer peptides, each containing a random sequence of 15 amino acids. Two clones showed binding affinities ranging from 166 to 520 nM. A conserved motif of four amino acids, DPGR, was identified. Clot formation of human plasma is inhibited by the selected clones, and they downregulate the thrombin-mediated activation of protein C. The identified peptide motifs do not share primary sequence similarities to any of the known natural thrombin binding motifs. As new inhibitors for human thrombin open interesting possibilities in thrombosis research, our newly identified peptides may provide further insights into this field of investigation and may be possible candidates for the development of new anti-thrombotic agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Blood Coagulation / drug effects
  • Dose-Response Relationship, Drug
  • Fibrinolytic Agents / chemistry
  • Fibrinolytic Agents / isolation & purification
  • Fibrinolytic Agents / pharmacology
  • Gene Expression Profiling
  • Humans
  • Peptide Library
  • Peptides / chemistry
  • Peptides / isolation & purification*
  • Peptides / pharmacology
  • Protein Binding
  • Protein C / drug effects
  • Thrombin / antagonists & inhibitors*
  • Thrombin / metabolism

Substances

  • Fibrinolytic Agents
  • Peptide Library
  • Peptides
  • Protein C
  • Thrombin