Synthesis and characterization of a sulfated and a non-sulfated cyclic CCK8 analogue functionalized with a chelating group for metal labelling.
Two cyclic peptides, cyclo29,34[Dpr29, Lys34(DTPA-Glu)]-CCK8 (1) and cyclo29,34[Tyr27(SO3H), Dpr29, Lys34(DTPA-Glu)]-CCK8 (2), bearing the chelating moiety DTPA-Glu covalently bound to the Lys side chain have been synthesized by solid-phase methodology. The presence in compound 2 of many acidic functions characteristic of the chelating agent increases the lability of the sulfate group on the Tyr side chain. This finding suggests that prolonged acid treatments should be avoided during the preparation of such peptides. Sulfation of cyclo29,34[Dpr29, Lys34(DTPA-Glu)]-CCK8 was performed using a pyridine-SO3 complex as reagent. This reaction has been found to be the most suitable synthetic strategy for obtaining compound 2 in good yield. Cyclo29,34[Tyr27(SO3H), Dpr29, Lys34(DTPA-Glu)]-CCK8 is a new promising CCK8 analogue, able to coordinate radioactive isotopes of metal ions such as 111In(III), and to bind, in a selective way, the CCKA-R receptor.
De Luca
Stefania
S
Centro Interuniversitario per la Ricerca sui Peptidi Bioattivi, Dipartimento di Chimica Biologica, Università di Napoli Federico II, 80134 Napoli, Italy.
Morelli
Giancarlo
G
D002614:Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism; D002766:Cholecystokinin / Q000737:chemistry*; D006801:Humans; D007205:Indium Radioisotopes / Q000737:chemistry* / Q000378:metabolism; D007553:Isotope Labeling; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011949:Receptors, Cholecystokinin / Q000378:metabolism; D013463:Sulfuric Acid Esters / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism; D014443:Tyrosine / Q000737:chemistry
D002614:Chelating Agents; D007205:Indium Radioisotopes; D010456:Peptides, Cyclic; D011949:Receptors, Cholecystokinin; D013463:Sulfuric Acid Esters; D014443:Tyrosine; D002766:Cholecystokinin