Budesonide and ciclesonide: effect of tissue binding on pulmonary receptor binding.

Newer inhaled glucocorticoids often show low systemic side effects because of their high protein binding. This study was interested in evaluating the effects of increased plasma protein and tissue binding on pulmonary receptor occupancy. Rats received des-ciclesonide (des-CIC; the active metabolite of the prodrug ciclesonide) and budesonide (BUD; a drug with lower protein binding but similar receptor affinity) as constant rate infusion over 6 h (intravenous bolus of 30 microg/kg, followed by 10 microg/h/kg over 6 h).

Synthesis and pharmacological evaluation of an analogue of the peptide hormone oxytocin that contains a mimetic of an inverse gamma-turn.

Oxytocin is a neurohypophyseal peptide hormone that induces labor and lactation in mammals. An inverse gamma-turn mimetic corresponding to the tripeptide Ile-Val-Asn has been synthesized and incorporated instead of residues 3-5 of oxytocin to probe the hypothesis that a gamma-turn involving these residues is found in the receptor bound conformation of oxytocin. In the turn mimetic, residues i and i + 1 are connected by a psi[CH(2)O] isostere while a covalent methylene bridge replaces the hydrogen bond that is often found between residues i and i + 2 in gamma-turns.

Conformations and receptor activity of desmopressin analogues, which contain gamma-turn mimetics or a psi[CH(2)O] isostere.

Three analogues of the antidiuretic drug desmopressin ([1-desamino,8-D-arginine]vasopressin) have been prepared. In two of these, gamma-turn mimetics based on a morpholin-3-one framework have been inserted instead of residues Phe3-Asn5, whereas the third analogue has a methylene ether isostere in place of the amide bond between residues 3 and 4. The three analogues were used to probe if the structure determined for desmopressin in aqueous solution, which contains an inverse gamma-turn centered around Gln4, is important in interactions with the vasopressin V(2) receptor.