77614-16-5Relevant articles and documents
A Blocking Group Scan Using a Spherical Organometallic Complex Identifies an Unprecedented Binding Mode with Potent Activity In Vitro and In Vivo for the Opioid Peptide Dermorphin
Strack, Martin,Bedini, Andrea,Yip, King T.,Lombardi, Sara,Siegmund, Daniel,Stoll, Raphael,Spampinato, Santi M.,Metzler-Nolte, Nils
, p. 14605 - 14610 (2016)
Herein, the selective enforcement of one particular receptor-ligand interaction between specific domains of the μ-selective opioid peptide dermorphin and the μ opioid receptor is presented. For this, a blocking group scan is described which exploits the steric demand of a bis(quinolinylmethyl)amine rhenium(I) tricarbonyl complex conjugated to a number of different, strategically chosen positions of dermorphin. The prepared peptide conjugates lead to the discovery of two different binding modes: An expected N-terminal binding mode corresponds to the established view of opioid peptide binding, whereas an unexpected C-terminal binding mode is newly discovered. Surprisingly, both binding modes provide high affinity and agonistic activity at the μ opioid receptor in vitro. Furthermore, the unprecedented C-terminal binding mode shows potent dose-dependent antinociception in vivo. Finally, in silico docking studies support receptor activation by both dermorphin binding modes and suggest a biological relevance for dermorphin itself. Relevant ligand-protein interactions are similar for both binding modes, which is in line with previous protein mutation studies.
Iodotrichlorosilane as Nα-Z cleaving agent in solid phase synthesis of dermorphin and oxytocin
Sivanandaiah, K. M.,Babu, V. V. Suresh,Renukeshwar, H. C.,Gangadhar, B. P.
, p. 487 - 491 (2007/10/02)
Iodotrichlorosilane, prepared by mixing freshly distilled silicon tetrachloride and sodium or potassium iodide, can be used for the efficient cleavage of Nα-benzyloxycarbonyl group in stepwise solid phase peptide synthesis.Thus, the opioid heptapeptide, dermorphin and the pituitary hormone, oxytocin have been synthesized in good yield and purity.
Structure-Activity Studies of Dermorphin. Synthesis and Some Pharmacological Data of Dermorphin and Its 1-Substiituted Analogues
Darlak, Krzysztof,Grzonka, Zbigniew,Janicki, Piotr,Czlonkowski, Andrzej,Gumulka, S. Witold
, p. 1445 - 1447 (2007/10/02)
Dermorphin and its analogues substituted at position 1 by N-acetyltyrosine, O-methyltyrosine, phenylalanine, D-phenylalanine, or alanine were obtained by solid-phase peptide synthesis.Their pharmacological effects were studied in vitro by the guinea pig ileum method and in vivo by the hot plate method, and the results were compared with those of morphine.The most pronounced activity was shown for dermorphin.A radioreceptor study showed a moderate affinity of dermorphin and its Tyr(Me)1 analogue for the opiate receptor sites from striatal homogenates.
