Engineering pro-angiogenic peptides using stable, disulfide-rich cyclic scaffolds.

Publisher: Elsevier Country of Publication: United States NLM ID: 7603509 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1528-0020 (Electronic) Linking ISSN: 00064971 NLM ISO Abbreviation: Blood Subsets: MEDLINE

Publication: 2021- : [New York] : Elsevier
Original Publication: New York, Grune & Stratton [etc.]

Angiogenic Proteins/*chemistry ; Disulfides/*chemistry ; Peptides, Cyclic/*chemistry ; Protein Engineering/*methods; Amino Acid Sequence ; Angiogenic Proteins/genetics ; Angiogenic Proteins/pharmacology ; Animals ; Cells, Cultured ; Chick Embryo ; Chorioallantoic Membrane/blood supply ; Chorioallantoic Membrane/drug effects ; Cyclotides/chemistry ; Cyclotides/genetics ; Cyclotides/pharmacology ; Dose-Response Relationship, Drug ; Endothelial Cells/drug effects ; Endothelial Cells/physiology ; Hemolysis/drug effects ; Humans ; Models, Molecular ; Molecular Sequence Data ; Neovascularization, Physiologic/drug effects ; Peptides, Cyclic/genetics ; Peptides, Cyclic/pharmacology ; Protein Conformation ; Protein Stability ; Rats

Fragments from the extracellular matrix proteins laminin and osteopontin and a sequence from VEGF have potent proangiogenic activity despite their small size (< 10 residues). However, these linear peptides have limited potential as drug candidates for therapeutic angiogenesis because of their poor stability. In the present study, we show that the therapeutic potential of these peptides can be significantly improved by "grafting" them into cyclic peptide scaffolds. Momordica cochinchinensis trypsin inhibitor-II (MCoTI-II) and sunflower trypsin inhibitor-1 (SFTI-1), naturally occurring, plant-derived cyclic peptides of 34 and 14 residues, respectively, were used as scaffolds in this study. Using this approach, we have designed a peptide that, in contrast to the small peptide fragments, is stable in human serum and at nanomolar concentration induces angiogenesis in vivo. This is the first report of using these scaffolds to improve the activity and stability of angiogenic peptide sequences and is a promising approach for promoting angiogenesis for therapeutic uses.

0 (Angiogenic Proteins)
0 (Cyclotides)
0 (Disulfides)
0 (Peptides, Cyclic)
0 (SFTI-1 peptide, sunflower)
0 (trypsin inhibitor MCoTI-II)

Date Created: 20111101 Date Completed: 20120316 Latest Revision: 20210206

20250114

10.1182/blood-2011-06-359141

22039263