Peptide backbone modifications on the C-terminal hexapeptide of neurotensin.
To compare backbone-induced susceptibilities with affinity changes that are caused by side-chain modifications in the respective positions, structure activity relationship studies on a series of NT(8-13) analogues were performed providing valuable insights into the major requirement for neurotensin receptor recognition and activation. The data led us to highly potent NTR1 ligands and the generation of a pharmacophore model that will be helpful for the discovery of therapeutically relevant non-peptidic NTR1 agonists.
Einsiedel
Jürgen
J
Department of Chemistry and Pharmacy, Emil Fischer Center, Friedrich Alexander University, D-91052 Erlangen, Germany.
Hübner
Harald
H
Hervet
Maud
M
Härterich
Steffen
S
Koschatzky
Susanne
S
Gmeiner
Peter
P
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015394:Molecular Structure; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics; D009496:Neurotensin / Q000737:chemistry* / Q000378:metabolism; D010165:Palladium / Q000494:pharmacology; D010446:Peptide Fragments / Q000737:chemistry*; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018028:Receptors, Neurotensin / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013329:Structure-Activity Relationship; D013552:Swine
D010446:Peptide Fragments; D012333:RNA, Messenger; D018028:Receptors, Neurotensin; C114036:neurotensin type 1 receptor; D009496:Neurotensin; D010165:Palladium; D002118:Calcium