Premium
Glycation Methods for Bombesin Analogs Containing the ( N α His)Ac chelator for 99m Tc(CO) 3 Radiolabeling
Author(s) -
Brans Luc,
Maes Veronique,
GarcíaGarayoa Elisa,
Schweinsberg Christian,
Daepp Simone,
Bläuenstein Peter,
August Schubiger P.,
Schibli Roger,
Tourwé Dirk A.
Publication year - 2008
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2008.00727.x
Subject(s) - bombesin , chemistry , glycation , peptide , biodistribution , receptor , gastrin , biochemistry , gastrin releasing peptide , in vitro , neuropeptide , secretion
The overexpression of peptide receptors in a variety of human carcinomas has generated considerable interest in peptide‐based radiopharmaceuticals for peptide receptor imaging and peptide receptor radiotherapy. The gastrin‐releasing peptide receptor is overexpressed in human prostate‐, breast‐, colon‐ and small cell lung carcinoma cells. We have developed metabolically stable 99m Tc‐radiolabeled bombesin ([Cha 13 , Nle 14 ]BBS(7–14)) analogs, which bind with high affinity to the gastrin‐releasing peptide receptors. However, because of their lipophilicity, they showed unfavorable biodistribution with high hepatic accumulation and hepatobiliary excretion. We now report a study of different glycation methods for [Cha 13 , Nle 14 ]BBS(7–14) analogs to improve their biodistribution profile. Whereas the glycation using the Maillard reaction was problematic, resulting in low yields, selective introduction of the glycomimetic shikimic acid to the side chain of a Lys residue was possible. A chemoselective ligation of α‐ d ‐glucose to an amino‐oxyacetylated [Cha 13 , Nle 14 ]BBS(7–14) analog could be achieved, but was complicated by the co‐elution of starting peptide and glycopeptide. The best procedure consisted of the [1,3]‐cycloaddition of N 3 ‐β‐ d ‐glucose to a propargylglycine‐containing [Cha 13 , Nle 14 ]BBS(7–14) analog, using a catalytic amount of Cu(I)I. All glycated [Cha 13 , Nle 14 ]BBS(7–14) analogs showed high affinity for the gastrin‐releasing peptide receptor and rapid accumulation into PC‐3 tumor cells.