title: Receptor-mediated uptake of boron-rich neuropeptide y analogues for boron neutron capture therapy.
abstract: Peptidic ligands selectively targeting distinct G protein-coupled receptors that are highly expressed in tumor tissue represent a promising approach in drug delivery. Receptor-preferring analogues of neuropeptide Y (NPY) bind and activate the human Y1 receptor subtype (hY1 receptor), which is found in 90% of breast cancer tissue and in all breast-cancer-derived metastases. Herein, novel highly boron-loaded Y1 -receptor-preferring peptide analogues are described as smart shuttle systems for carbaboranes as (10) B-containing moieties. Various positions in the peptide were screened for their susceptibility to carbaborane modification, and the most promising positions were chosen to create a multi-carbaborane peptide containing 30 boron atoms per peptide with excellent activation and internalization patterns at the hY1 receptor. Boron uptake studies by inductively coupled plasma mass spectrometry revealed successful uptake of the multi-carbaborane peptide into hY1 -receptor-expressing cells, exceeding the required amount of 10(9) boron atoms per cell. This result demonstrates that the NPY/hY receptor system can act as an effective transport system for boron-containing moieties.
authors.affiliation: Institute of Biochemistry, Universität Leipzig, Brüderstrasse 34, 04103 Leipzig (Germany).
authors.forename: Verena M
authors.initials: VM
authors.lastname: Ahrens
authors.forename: René
authors.initials: R
authors.lastname: Frank
authors.forename: Solveig
authors.initials: S
authors.lastname: Boehnke
authors.forename: Christian L
authors.initials: CL
authors.lastname: Schütz
authors.forename: Gabriele
authors.initials: G
authors.lastname: Hampel
authors.forename: Dorothée S
authors.initials: DS
authors.lastname: Iffland
authors.forename: Nicolas H
authors.initials: NH
authors.lastname: Bings
authors.forename: Evamarie
authors.initials: E
authors.lastname: Hey-Hawkins
authors.forename: Annette G
authors.initials: AG
authors.lastname: Beck-Sickinger
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001880:Boranes / Q000138:chemical synthesis / Q000737:chemistry*; D016754:Boron Neutron Capture Therapy; D001943:Breast Neoplasms / Q000532:radiotherapy; D019556:COS Cells; D002522:Chlorocebus aethiops; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008969:Molecular Sequence Data; D009478:Neuropeptide Y / Q000031:analogs & derivatives / Q000378:metabolism*; D017476:Receptors, Neuropeptide Y / Q000235:genetics / Q000378:metabolism*
chemical_list: D001880:Boranes; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y
keywords: boron neutron capture therapy; cellular uptake; neuropeptide Y; peptides; solid-phase synthesis