Abstract
Regulatory, receptor‐binding peptides are considered as the agents of choice for diagnostic imaging and therapy of cancers, because their receptors are overexpressed in various human cancer cells. It has been recently indicated that there is a putative role of NPY in breast tumors. The expression of the two best‐investigated NPY receptor subtypes, Y~1~ and Y~2~, in breast tissue shows predominant occurrence of the Y~1~ receptor subtype in tumors, whereas Y~2~ receptors are found in nonproliferative tissue. To investigate the usefulness of NPY analogs for tumor diagnosis and therapy, we investigated the metabolic stability of receptor‐selective NPY analogs in human blood plasma. NPY analogs were synthesized by Fmoc/t‐Bu solid‐phase strategy. Prior to the cleavage of peptides from the resin, they were labeled with 5(6)‐carboxyfluorescein (CF) either at the N‐terminus or at the side chain of Lys^4^. For the metabolic stability study, the digestion of peptides was monitored by HPLC and the cleavage products were identified by MALDI‐ToF mass spectrometry. The data showed that full‐length [Phe^7^, Pro^34^]NPY analogs, which show high binding affinity to Y~1~ receptors are enzymatically more stable than centrally truncated analogs, which show high binding affinity to Y~2~ receptors. Furthermore, the N‐terminally CF‐labeled Y~1~ and Y~2~ receptor‐selective peptides were found to be enzymatically more resistant than their counterparts containing the CF label at Lys^4^ side chain. © 2007 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 88: 182–189, 2007.
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