We report the discovery of conopressin-T, a novel bioactive peptide isolated 
from Conus tulipa venom. Conopressin-T belongs to the vasopressin-like peptide 
family and displays high sequence homology to the mammalian hormone oxytocin 
(OT) and to vasotocin, the endogenous vasopressin analogue found in teleost 
fish, the cone snail's prey. Conopressin-T was found to act as a selective 
antagonist at the human V 1a receptor. All peptides in this family contain two 
conserved amino acids within the exocyclic tripeptide (Pro7 and Gly9), which are 
replaced with Leu7 and Val9 in conopressin-T. Whereas conopressin-T binds only 
to OT and V 1a receptors, an L7P analogue had increased affinity for the V 1a 
receptor and weak V2 receptor binding. Surprisingly, replacing Gly9 with Val9 in 
OT and vasopressin revealed that this position can function as an 
agonist/antagonist switch at the V 1a receptor. NMR structures of both 
conopressin-T and L7P analogue revealed a marked difference in the orientation 
of the exocyclic tripeptide that may serve as templates for the design of novel 
ligands with enhanced affinity for the V 1a receptor.