SHORT-CHAIN PEPTIDE DYE CONJUGATES AS CONTRASTING AGENTS FOR OPTICAL DIAGNOSTICS

摘要

Conjugates (I) of vasoactive intestinal peptide (VIP), somatostatin or neurotensin peptides and polymethine dyes are new. Peptide-dye conjugates of formula (I) are new. X = a sequence of 5-30 alpha -, beta - or gamma -amino acids (D or L) corresponding to the amino acid sequence of VIP, somatostatin or neurotensin or a fragment, derivative or analog thereof, optionally cyclized by a disulfide bridge between two cysteines or by an amide bridge between the N and C termini; A1 = H, acetyl, 1-10C alkyl (optionally substituted by 1-3 COOH groups and/or 1-6 OH groups), a polyoxyethylene group comprising 2-30 CH2CH2O units, or a polymethine dye having at least one absorption maximum in the 380-1200 nm range; and A2 = OH, NH2 or a polymethine dye having at least one absorption maximum in the 380-1200 nm range; provided that at least one of A1 and A2 is a polymethine dye, that when A1 is a polymethine dye, it is bonded to the N-terminal amino group and that when A2 is a polymethine dye, it is bonded to a lysine amino group or serine hydroxy group at any position within X. Independent claims are also included for the following: (1) a diagnostic method comprising administering (I) to a patient, either intravenously or to the bronchi by inhalation or to the gastrointestinal tract, esophagus or bladder by spraying and then washing out excess (I), and then performing an endoscopic investigation by local excitation of fluorescence at an excitation wavelength of 350-1200 nm and site-specific detection of the fluorescence emitted by the dye; and (2) cyanine dyes of formula (II). p = 1-3; n = 1-4 or 10; R1, R2 = 4-sulfobutyl, 3-sulfopropyl, 2-sulfoethyl, 3-methyl-3-sulfopropyl, methyl, ethyl or propyl; R3 = H, COOE1, CONE1E2, NHCOE1, NHCONHE1, NE1E2, OE1, OSO3E1, SO3E1 or SO2NHE1; and E1, E2 = H, CH3, ethyl, or 3-6C alkyl optionally interrupted by 1-2 O atoms and/or a CO group and/or optionally substituted by 1-5 OH groups.