Neurologically active plant compounds and peptide hormones: a chirality connection

The most dramatic, but seldom mentioned, difference between alkaloid and pe ptide opioids is the change of chirality of the a carbon of the tyramine mo iety. We propose that the presence of Gly(2) or D-Ala(2) in the two most co mmon message domains compensates this change by allowing the attainment of unusual conformations. A thorough conformational search of Tyr-D-Ala-Phe-NH -CH3 and of its isomer Tyr-L-Ala-Phe-NH-CH3 backs this view and establishes a solid link between alkaloid and peptide opioids. This finding supports t he notion that morphine, like other neurologically active plant compounds, may bind to endogenous receptors in plants to regulate cell-to-cell signali ng systems. (C) 1999 Federation of European Biochemical Societies.