Substance P derivatives with photoactivatable labels in the N‐terminal part of the molecule

Abstract

Photoactivatable substance P (SP) derivatives containing the p‐benzoylbenzoic moiety at the N‐terminal α‐amino group of Arg 1 or at the ε‐amino group of Lys 3 were prepared. Both derivatives also had a p‐hydroxyphenylpropionyl group for radioiodination. To obtain the analogue with the photolabel at Arg 1, SP was first reacted with N‐hydroxysuccinimide p‐hydroxyphenylpropionate, the Lys 3‐modified derivative was isolated by reversed‐phase high‐performance liquid chromatography (HPLC), reacted with N‐hydroxysuccinimide p‐benzoylbenzoate and purified by HPLC. To place the photolabel at Lys 3, the order of the reactions was reversed. The structure of the derivatives obtained was confirmed by mass spectrometry. The interaction of the derivatives obtained and of their 125I‐labeled forms with the NK‐1 neurokinin receptor from the rat brain, as well as with the nicotinic acetylcholine receptor from Torpedo electrocytes was analyzed. The results obtained supported by the data from the literature indicate that benzoylbenzoic acid derivatives should not be considered as universal photolabels, which ensure in all cases a high level of photo‐cross‐linking.

The Significance of NK1 Receptor Ligands and Their Application in Targeted Radionuclide Tumour Therapy

“…Multiple groups have recently published research concerning SP and its analogues or derivatives as agonistic or antagonistic peptide NK1R ligands [7,8,19,21,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65]. New unnatural peptides are designed in order to improve their biological properties (e.g., half-life, receptor affinity and lipophilicity).…”