title: Improved synthesis and biological evaluation of chelator-modified α-MSH analogs prepared by copper-free click chemistry.
abstract: Radionuclide chelators (DOTA, NOTA) functionalized with a monofluorocyclooctyne group were prepared. These materials reacted rapidly and in high yield with a fully deprotected azide-modified peptide via Cu-free click chemistry under mild reaction conditions (aqueous solution, room temperature). The resulting bioconjugates bind with high affinity and specificity to their cell-surface receptor targets in vitro and appear stable to degradation in mouse serum over 3h of incubation at 37°C.
authors.affiliation: Department of Radiology, Carver College of Medicine, The University of Iowa, 500 Newton Road, ML B180, Iowa City, IA 52242, USA.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Baumhover
authors.forename: Molly E
authors.initials: ME
authors.lastname: Martin
authors.forename: Sharavathi G
authors.initials: SG
authors.lastname: Parameswarappa
authors.forename: Kyle C
authors.initials: KC
authors.lastname: Kloepping
authors.forename: M Sue
authors.initials: MS
authors.lastname: O'Dorisio
authors.forename: F Christopher
authors.initials: FC
authors.lastname: Pigge
authors.forename: Michael K
authors.initials: MK
authors.lastname: Schultz
mesh_terms: D000818:Animals; D001386:Azides; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry*; D057930:Click Chemistry / Q000379:methods*; D003300:Copper; D003301:Copper Radioisotopes / Q000737:chemistry; D004353:Drug Evaluation, Preclinical; D004355:Drug Stability; D005710:Gallium Radioisotopes / Q000737:chemistry; D006571:Heterocyclic Compounds / Q000737:chemistry; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D006801:Humans; D051379:Mice; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D012680:Sensitivity and Specificity; D000521:alpha-MSH / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism
chemical_list: D001386:Azides; D002614:Chelating Agents; D003301:Copper Radioisotopes; D005710:Gallium Radioisotopes; D006571:Heterocyclic Compounds; D006573:Heterocyclic Compounds, 1-Ring; D019275:Radiopharmaceuticals; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; C048993:1,4,7-triazacyclononane-N,N',N''-triacetic acid; D000521:alpha-MSH; D003300:Copper