title: Identification of targeting peptides for ischemic myocardium by in vivo phage display.
abstract: Therapies selectively targeting ischemic myocardium could be applied by intravenous injection. Here, we report an approach for ischemic tissue-selective targeting based on in vivo screening of random peptide sequences using phage display. We performed in vivo biopanning using a phage library in a rat model of ischemia-reperfusion and identified three peptide motifs, CSTSMLKAC, CKPGTSSYC, and CPDRSVNNC, that exhibited preferential binding to ischemic heart tissue compared to normal heart as well as other control organs. The CSTSMLKAC sequence was capable of mediating selective homing of phage to ischemic heart tissue. The CSTSMLKAC peptide was then made as a fusion protein with Sumo-mCherry and injected intravenously in a mouse model of myocardial ischemia-reperfusion injury; subsequently, bio-distribution of Sumo-mCherry-CSTSMLKAC was measured with quantitative ELISA. The targeting peptide led to a significant increase in homing to ischemic left ventricle compared to tissues from non-ischemic left ventricle, the right ventricle, lung, liver, spleen, skeletal muscle, and brain (all p<0.001). These results indicate that the peptide sequence CSTSMLKAC represents a novel molecular tool that may be useful in targeting ischemic tissue and delivering bioengineered proteins into the injured myocardium by systemic intravenous administration.
authors.affiliation: The Harvard Stem Cell Institute and the Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Cambridge, MA, USA.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Kanki
authors.forename: Diana E
authors.initials: DE
authors.lastname: Jaalouk
authors.forename: Samuel
authors.initials: S
authors.lastname: Lee
authors.forename: Alvin Y C
authors.initials: AY
authors.lastname: Yu
authors.forename: Joseph
authors.initials: J
authors.lastname: Gannon
authors.forename: Richard T
authors.initials: RT
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D008297:Male; D051379:Mice; D017202:Myocardial Ischemia / Q000188:drug therapy*; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D019151:Peptide Library; D010455:Peptides