Molecular Recognition of B-DNA Minor-Groove Binders: The Rigid Analogue Approach to Synthesise Antileishmaniasis Compounds: A Molecular Modeling Study

Aromatic bisamidines are active against Leishmania sp. and Pneumocystis carinii. The mode of action is not known, but it has been suggested that they bind to B-DNA minor grooves. Within the drug design based upon the receptor structure, we show the binding energies for some pentamidine analogues with B-DNA and results establish a common base for the synthesis of their rigid counterparts. This is done through the identification of pharmacophore conformation that is isohelical to B-DNA. Results also show the closer pharmacophoric conformation the better binding energies

beta-Arrestin-dependent constitutive internalization of the human chemokine decoy receptor D6

Seven transmembrane receptors mediate diverse physiological responses including hormone action, o1-faction, neurotransmission, and chemotaxis. Human D6 is a non-signaling seven-transmembrane receptor expressed on lymphatic endothelium interacting with most inflammatory CC-chemokines resulting in their rapid internalization. Here, we demonstrate that this scavenging activity is mediated by continuous internalization and constant surface expression of the receptor, a process involving the clathrin-coated pit-dependent pathway. D6 constitutively associates with the cytoplasmic adaptor \u3b2-arrestin, and this interaction is essential for D6 internalization. An acidic region, but not the putative phosphorylation sites in the cytoplasmic tail of D6, is critical for receptor interaction with \u3b2-arrestin and subsequent internalization. Neither the native D6 nor mutants uncoupled from \u3b2-arrestin activate any G-protein-mediated signaling pathways. Therefore, D6 may be considered a decoy receptor structurally adapted to perform chemokine scavenging

A Psychodynamic View of Counseling Psychology

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69032/2/10.1177_001100008000900114.pd