Synthesis and biological activity of N-terminal lipidated and/or fluorescently labeled conjugates of astressin as corticotropin releasing factor antagonists.
This report describes the synthesis of eight N-terminally modified astressin analogs and their biochemical evaluation as corticotropin releasing factor (CRF) antagonists. The lipidated astressin derivatives were tested on rat CRF receptor type 1 and 2alpha and were found to be active as CRF antagonists (rCRFR1: pA(2)=7.5-8.3; rCRFR2alpha: pA(2)=7.5-9.0) with nearly equal activities as compared to unmodified astressin (rCRFR1: pA(2)=8.3+/-0.09; rCRFR2alpha: pA(2)=8.7+/-0.08).
Rijkers
Dirk T S
DT
Department of Medicinal Chemistry, Utrecht Institute for Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Utrecht University, PO Box 80082, 3508 TB Utrecht, The Netherlands. d.t.s.rijkers@pharm.uu.nl <d.t.s.rijkers@pharm.uu.nl>
den Hartog
Jack A J
JA
Liskamp
Rob M J
RM
D000818:Animals; D002460:Cell Line; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D005456:Fluorescent Dyes / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D018019:Receptors, Corticotropin-Releasing Hormone; D013329:Structure-Activity Relationship; D001616:beta-Galactosidase / Q000032:analysis / Q000096:biosynthesis; D000099052:CRF Receptor, Type 1
C101531:CRF receptor type 2; D005456:Fluorescent Dyes; D008055:Lipids; D010446:Peptide Fragments; D018019:Receptors, Corticotropin-Releasing Hormone; C104416:astressin; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone; D000242:Cyclic AMP; D001616:beta-Galactosidase