TY - JOUR
T1 - A new strategy for the preparation of peptide-targeted technetium and rhenium radiopharmaceuticals. The automated solid-phase synthesis, characterization, labeling, and screening of a peptide-ligand library targeted at the formyl peptide receptor
AU - Stephenson, Karin A.
AU - Banerjee, Sangeeta Ray
AU - Sogbein, Oyebola O.
AU - Levadala, Murali K.
AU - McFarlane, Nicole
AU - Boreham, Douglas R.
AU - Maresca, Kevin P.
AU - Babich, John W.
AU - Zubieta, Jon
AU - Valliant, John F.
PY - 2005
Y1 - 2005
N2 - A new solid-phase, synthetic methodology was developed that enables libraries of peptide-based Tc-(I)/Re(I) radiopharmaceuticals to be prepared using a conventional automated peptide synthesizer. Through the use of a tridentate ligand derived from N-α-Fmoc-L-lysine, which we refer to as a single amino acid chelate (SAAC), a series of 12 novel bioconjugates [R-NH(CO)ZLF(SAAC)G, R = ethyl, isopropyl, n-propyl, tert-butyl, n-butyl, benzyl; Z = Met, Nle] that are designed to target the formyl peptide receptor (FPR) were prepared. Construction of the library was carried out in a multiwell format on an Advanced ChemTech 348 peptide synthesizer where multi-milligram quantities of each peptide were isolated in high purity without HPLC purification. After characterization, the library components were screened for their affinity for the FPR receptor using flow cytometry where the Ka values were found to be in the low micromolar range (0.5-3.0 μM). Compound 5j was subsequently labeled with 99mTc(I) and the product isolated in high radiochemical yield using a simple Sep-Pak purification procedure. The retention time of the labeled compound matched that of the fully characterized Re-analogue which was prepared through the use of the same solid-phase synthesis methodology that was used to construct the library. The work reported here is a rare example of a method by which libraries of peptide-ligand conjugates and their rhenium complexes can be prepared.
AB - A new solid-phase, synthetic methodology was developed that enables libraries of peptide-based Tc-(I)/Re(I) radiopharmaceuticals to be prepared using a conventional automated peptide synthesizer. Through the use of a tridentate ligand derived from N-α-Fmoc-L-lysine, which we refer to as a single amino acid chelate (SAAC), a series of 12 novel bioconjugates [R-NH(CO)ZLF(SAAC)G, R = ethyl, isopropyl, n-propyl, tert-butyl, n-butyl, benzyl; Z = Met, Nle] that are designed to target the formyl peptide receptor (FPR) were prepared. Construction of the library was carried out in a multiwell format on an Advanced ChemTech 348 peptide synthesizer where multi-milligram quantities of each peptide were isolated in high purity without HPLC purification. After characterization, the library components were screened for their affinity for the FPR receptor using flow cytometry where the Ka values were found to be in the low micromolar range (0.5-3.0 μM). Compound 5j was subsequently labeled with 99mTc(I) and the product isolated in high radiochemical yield using a simple Sep-Pak purification procedure. The retention time of the labeled compound matched that of the fully characterized Re-analogue which was prepared through the use of the same solid-phase synthesis methodology that was used to construct the library. The work reported here is a rare example of a method by which libraries of peptide-ligand conjugates and their rhenium complexes can be prepared.
UR - http://www.scopus.com/inward/record.url?scp=25444437726&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=25444437726&partnerID=8YFLogxK
U2 - 10.1021/bc0500591
DO - 10.1021/bc0500591
M3 - Article
C2 - 16173797
AN - SCOPUS:25444437726
SN - 1043-1802
VL - 16
SP - 1189
EP - 1195
JO - Bioconjugate Chemistry
JF - Bioconjugate Chemistry
IS - 5
ER -