Double bond isosteres of the peptide bond: synthesis and biological activity of cholecystokinin (CCK) C-terminal hexapeptide analogs.
New and existing methodologies were used to prepare a series of modified CCK analogs in which each amide bond was replaced by a trans-alkene unit. The data indicate that every amide linkage at C-terminal tetrapeptide (CCK-4) region is crucial for biological activity. While the amide bond beyond the Trp residue in the N-terminal direction can be replaced by a trans-alkene and still retain most of the binding potency and functional activity.
Shue
Y K
YK
Pharmaceutical Product Division, Abbott Laboratories, Abbott Park, IL 60064.
Tufano
M D
MD
Carrera
G M
GM
Kopecka
H
H
Kuyper
S L
SL
Holladay
M W
MW
Lin
C W
CW
Witte
D G
DG
Miller
T R
TR
Stashko
M
M
D000595:Amino Acid Sequence; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D002766:Cholecystokinin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010179:Pancreas / Q000378:metabolism; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D011869:Radioligand Assay; D013329:Structure-Activity Relationship
D010446:Peptide Fragments; D002766:Cholecystokinin