No abstract

Neuropeptide Y (NPY) receptors belong to the G-protein-coupled receptor (GPCR) superfamily and mediate several physiological responses, such as blood pressure, food intake, sedation and memory retention. To understand the interactions between the NPY Y1 receptor subtype and its ligands, computer modeling was applied to the natural peptide agonist, NPY and a small molecule antagonist, BIBP3226. An agonist and antagonist binding domain was elucidated using mutagenesis data for the Y1 receptor as well as for other GPCR families. The agonist and antagonist ligands which were investigated appear to share common residues for their interaction within the transmembrane regions of the Y1 receptor structure, including Gln120, Asn283 and His306. This is in contrast to findings with tachykinin receptors where the binding domains of the non-peptide antagonists have very little in common with the binding domains of the agonist, substance-P. In addition, a hydrogen bond between the hydroxyl group of Tyr36 of NPY and the side chain of Gln219, an interaction that is absent in the model complex between Y1 and the antagonist BIBP3226, is proposed as one of the potential interactions necessary for receptor activation.

No abstract

No abstract

SummarySeveral attempts to prepare 3-acetyl-5-benzyl-3-pyrrolin-2-one (7) from phenylalanine are described. This goal was only reached formally, because compound 7 exists in the tautomeric form of (Z)-5-benzyl-3-(1'-hydroxyethylidene)-4-pyrrolin-2-one (17) according to the spectral data. The problem of tautomerism in pyrrolinone systems is discussed.The formation of an appropriate pyrrolinone system represents a major task in any synthetic approach toward cytochalasans [ 2 ] . Several studies have been carried out for the construction of this part of the molecule which should serve as a basic unit for the annelation of the cyclohexane ring. Because a cis ring-fusion is required for the resulting octahydroisoindolone system, a Diels-Alder reaction was used for its formation. Some difficulties arose, however, with respect to the introScheme 1 duction of the functionality R which should allow an easy completion of the macrocyclic system. The substituent R may either be present already in the dienophile, or may be inserted after the elaboration of the condensed ring system (Scheme 1). The first approach has been used in early attempts by several authors