TY - JOUR
T1 - Backbone metal-cyclization
T2 - A novel approach for simultaneous peptide cyclization and radiolabeling. Application to the combinatorial synthesis of rhenium-cyclic somatostatin analogs
AU - Fridkin, Gil
AU - Bonasera, Thomas A.
AU - Litman, Pninit
AU - Gilon, Chaim
PY - 2005/1
Y1 - 2005/1
N2 - A novel approach for the combinatorial synthesis of backbone-derived metal-cyclic peptide libraries is presented. In this approach the metalo-cyclic peptides are prepared from their linear precursors through complexation of a metal atom via two hemi-chelating arms located on the peptide backbone. Thus, cyclization and metal labeling of the peptides are achieved simultaneously. A library, composed of 48 rhenium-cyclic somatostatin analogs, was prepared. All rhenium somatostatin complexes exhibited high to moderate in vitro binding affinities toward cloned human somatostatin receptor subtype 2 (hsstr2). Five rhenium-cyclic peptides were found to be most potent with IC50 values between 1 and 3 nM making them promising leads for further development of tumor diagnostic and therapeutic radiolabeled agents. A 99mTc somatostatin cyclic analog was successfully prepared by the same method.
AB - A novel approach for the combinatorial synthesis of backbone-derived metal-cyclic peptide libraries is presented. In this approach the metalo-cyclic peptides are prepared from their linear precursors through complexation of a metal atom via two hemi-chelating arms located on the peptide backbone. Thus, cyclization and metal labeling of the peptides are achieved simultaneously. A library, composed of 48 rhenium-cyclic somatostatin analogs, was prepared. All rhenium somatostatin complexes exhibited high to moderate in vitro binding affinities toward cloned human somatostatin receptor subtype 2 (hsstr2). Five rhenium-cyclic peptides were found to be most potent with IC50 values between 1 and 3 nM making them promising leads for further development of tumor diagnostic and therapeutic radiolabeled agents. A 99mTc somatostatin cyclic analog was successfully prepared by the same method.
KW - Backbone metal-cyclization
KW - Radiolabeled somatostatin analogs
UR - http://www.scopus.com/inward/record.url?scp=13244299209&partnerID=8YFLogxK
U2 - 10.1016/j.nucmedbio.2004.08.007
DO - 10.1016/j.nucmedbio.2004.08.007
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C2 - 15691660
AN - SCOPUS:13244299209
SN - 0969-8051
VL - 32
SP - 39
EP - 50
JO - Nuclear Medicine and Biology
JF - Nuclear Medicine and Biology
IS - 1
ER -