Synthesis and biological evaluation of cyclic and branched peptide analogues as ligands for cholecystokinin type 1 receptor.
A library of cyclic CCK8 analogues, containing unnatural amino acids in the peptide sequence, is prepared using solid-phase synthesis. The structure of these cyclic peptides is based on a previously synthesised compound, cyclo-CCK8, selective for CCK(1) receptor. Structure-activity investigations are performed by evaluating the binding properties of the new analogues. In particular, the binding ability of the cyclic CCK8 analogues is tested by nuclear medicine studies on cell line transfected with CCK(1) receptor. Compounds named cyclo-A4-cyclo-A7 show binding constant in the range 6.0-8.0 microM, with an improved affinity over the previous described cyclo-CCK8, but almost comparable IC(50) values among new analogues towards CCK(1) were obtained.
De Luca
Stefania
S
Istituto di Biostrutture e Bioimmagini CNR, & Centro Interuniversitario per la Ricerca sui Peptidi Bioattivi (CIRPeB), via Mezzocannone, Napoli, Italy.
De Capua
Antonia
A
Saviano
Michele
M
Della Moglie
Raffaella
R
Aloj
Luigi
L
Tarallo
Laura
L
Pedone
Carlo
C
Morelli
Giancarlo
G
D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D003500:Cyclization; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D019151:Peptide Library; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D011949:Receptors, Cholecystokinin / Q000378:metabolism*; D013329:Structure-Activity Relationship
D008024:Ligands; D019151:Peptide Library; D010455:Peptides; D011949:Receptors, Cholecystokinin