Design, synthesis and biological activity of carbohydrate-containing peptidomimetics as new ligands for the human tachykinin NK-2 receptor.
Enantiopure cycloadducts between glycals and alkyl or aryl heterodienes were selected as small, rigid, nonpeptide molecules able to superimpose to the structure of the cyclopeptide tachykinin NK-2 antagonist 1. The presence of three aromatic groups in the pyranose ring resulted essential for NK-2 affinity, while an increase in activity was shown by the corresponding sulfoxides.
Capozzi
Giuseppe
G
Dipartimento di Chimica Organica Ugo Schiff, Universita' di Firenze, via della Lastruccia, 13, I-50019 Sesto Fiorentino, Florence, Italy.
Giannini
Sabrina
S
Menichetti
Stefano
S
Nativi
Cristina
C
Giolitti
Alessandro
A
Patacchini
Riccardo
R
Perrotta
Enzo
E
Altamura
Maria
M
Alberto Maggi
Carlo
C
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D015195:Drug Design; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D018716:Molecular Mimicry; D009005:Monosaccharides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000494:pharmacology; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013440:Sulfides; D013450:Sulfones; D014162:Transfection
D008024:Ligands; D009005:Monosaccharides; D009842:Oligopeptides; D010456:Peptides, Cyclic; D018041:Receptors, Neurokinin-2; D013440:Sulfides; D013450:Sulfones