ABSTRACT
Two glycosylated peptides have been studied using NMR spectroscopy supported by molecular modeling. Peptide I is an oxytocin (OT) analogue in which glutamine 4 was replaced by serine with attached α-d-mannose through the oxygen β atom, whereas peptide II is a lysine-vasopressin (LVP) analogue with lysine 8 side chain modified by the attachment of glucuronic acid through an amide bond. Both peptides exhibit very weak uterotonic effect and are less susceptible to proteolytic degradation than the mother hormones. Additionally, peptide II reveals very weak pressor and antidiuretic activities. Our results have shown that the conformational preferences of glycosylated analogues are highly similar to those of their respective mother hormones. OT glycosylated analogue (I) exhibits a 3,4 β-turn characteristic of OT-like peptides, and vasopressin-glycosylated analogue (II) exhibits β-turns typical of vasopressin-like peptides. Therefore, the lack of binding of the glycosylated analogues to the receptors can be attributed to a steric interference between the carbohydrate moieties and the receptors. We also consider this to be the reason of the very low activity of the analyzed glycopeptides. We expect that results from these studies will be helpful in designing new OT-like and vasopressin-like drugs. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.
The introduction of the sterically restricted bulky glycoconjugates significantly reduces the activity of the neurohypophyseal hormones analogues. We consider that the reason of this can be steric repulsion between the carbohydrate moiety and the receptors. Therefore, despite that oxytocin-glycosylated analogue I exhibits 3,4 β-turn characteristic of oxytocin-like peptides and vasopressin-glycosylated analogue II exhibits β-turns typical of vasopressin-like peptides, these analogues have very low activity.