[Lys(DOTA)4]BVD15, a novel and potent neuropeptide Y analog designed for Y1 receptor-targeted breast tumor imaging

Identification of a Cyanine-Dye Labeled Peptidic Ligand for Y1R and Y4R, Based upon the Neuropeptide Y C-Terminal Analogue, BVD-15

“…21 This peptide has been amenable to conjugation with a variety of radiolabels and fluorophores. In particular, Gueŕin et al showed that the Ileconjugated Lys to incorporate DOTA, NOTA or fluorine moieties, 22,23 and we extended this result to include a rhodamine fluorophore. 24 No less notably, the Lys 4 substitution itself resulted in increased affinity, 23 and other basic residues were also well tolerated.…”

“…We extended the types of conjugates included at Lys 4 , but also encompassed substitutions at Asn 2 . While a lysine residue at the 2-position had been shown to be detrimental to Y1R activity, 23 the influence on subsequent conjugation had not been tested.…”

Red-fluorescent argininamide-type NPY Y1 receptor antagonists as pharmacological tools

“…Except for 40 these compounds were prepared by coupling of the corresponding Nprotected (Boc, Cbz) x-aminocarboxylic acids (16,17,19,23,24,28,35) to building block 12 or 30 (synthesis described previously) 6 with the aid of 1,1 0 -carbonyldiimidazole (CDI) (Scheme 3). The protected intermediates were purified by column chromatography prior to Boc-or Cbz-deprotection yielding the amines.…”

“…The Y 1 R was selected as a representative model of a peptidergic GPCR, for instance, as this receptor subtype was recently associated with diagnosis and treatment of tumours. [11][12][13][14][15][16][17][18][19] For the synthesis of non-peptidic fluorescent ligands, the argininamidetype Y 1 R selective antagonists BIBP 3226 20 and BIBO 3304 21 ( Fig. 1) were considered appropriate parent molecules to construct high affinity fluorescent probes with reduced propensity to induce internalisation compared to (peptidic) agonists.…”

Getting beta all the time: discovery of reliable markers of beta cell mass

“…This is in part because of their ill-defined cellular localisation and intractability to molecular cloning. Hence much of the development of imaging technologies for islets based on positron emission tomography and single photon emission computed tomography has been directed towards the use of high-affinity ligands of plasma membrane receptors such as glucagon-like peptide 1 (GLP-1) [8][9][10] and neuropeptide Y (NPY) [11], membrane channel components such as vesicular monoamine transporter 2 (VMAT2) [12], and the Kir6.2/sulfonylurea receptor complex, or more general metabolic functional markers [13].…”