Synthesis and evaluation of novel multimeric neurotensin(8-13) analogs.
Neurotensin(8-13) is a hexapeptide with subnanomolar affinity to the neurotensin receptor 1 which is expressed with high incidence in several human tumor entities. Thus, radiolabeled neurotensin(8-13) might be used for tumor targeting. However, its application is limited by insufficient metabolic stability. The present study aims at improving metabolic stability by the synthesis of multimeric neurotensin(8-13) derivatives rather than commonly employed chemical modifications of the peptide itself. Thus, different dimeric and tetrameric peptides carrying C- or N-terminal attached neurotensin(8-13) moieties have been synthesized and their binding affinity toward the neurotensin receptor has been determined. The results demonstrate that branched compounds containing neurotensin(8-13) attached via its C-terminus only show low receptor affinities, whilst derivatives with neurotensin(8-13) attached via the N-terminus show IC50 values in the nanomolar range. Moreover, within the multimeric neurotensin(8-13) derivatives with neurotensin(8-13) attached via the N-terminus an increasing number of branching units lead to higher binding affinities toward the neurotensin receptor.
Hultsch
Christina
C
Institute of Radiopharmacy, Research Center Rossendorf, Germany.
Pawelke
Beate
B
Bergmann
Ralf
R
Wuest
Frank
F
D000595:Amino Acid Sequence; D019073:HT29 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D009496:Neurotensin / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding; D018028:Receptors, Neurotensin / Q000737:chemistry / Q000378:metabolism
D010446:Peptide Fragments; D018028:Receptors, Neurotensin; D009496:Neurotensin; C054381:neurotensin (8-13)