title: Use of N,O-bis-Fmoc-D-Tyr-ONSu for introduction of an oxidative iodination site into cholecystokinin family peptides.
abstract: We report the synthesis of a new reagent for the introduction of an oxidative iodination site into the amino terminus of acid-labile peptides, and the use of this reagent to synthesize a novel affinity-labeling probe for the cholecystokinin (CCK) receptor. The acylation reagent, N,O-bis-fluorenylmethyloxycarbonyl-D-tyrosine hydroxysuccinimide ester, utilizes base-labile protection of both the alpha amino group and the aromatic ring hydroxyl. This can be safely removed to expose a cross-linkable free amino group on the aminopeptidase-resistant D-enantiomer of tyrosine. The synthetic probe, D-Tyr-Gly-Asp-Tyr(OSO3H)-Nle-Gly-Trp-Nle-Asp-Phe-NH2, was fully biologically active, could be radioiodinated to high-specific radioactivity (2000 Ci/mmol), bound with high affinity to the pancreatic CCK receptor, and covalently labeled the hormone-binding site. This reagent should be useful for the synthesis of a wide variety of analogues of CCK and other acid-labile peptides.
authors.affiliation: Gastroenterology Research Unit, Mayo Clinic and Foundation, Rochester, MN.
authors.forename: S P
authors.initials: SP
authors.lastname: Powers
authors.forename: D I
authors.initials: DI
authors.lastname: Pinon
authors.forename: L J
authors.initials: LJ
authors.lastname: Miller
mesh_terms: D000345:Affinity Labels / Q000138:chemical synthesis*; D002766:Cholecystokinin / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D007457:Iodine Radioisotopes; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D013329:Structure-Activity Relationship; D013388:Succinimides; D014443:Tyrosine / Q000031:analogs & derivatives
chemical_list: D000345:Affinity Labels; D007202:Indicators and Reagents; D007457:Iodine Radioisotopes; D013388:Succinimides; C056981:N,O-bis(fluorenylmethyloxycarbonyl)tyrosine hydroxysuccinimide ester; D014443:Tyrosine; D002766:Cholecystokinin