Dopamine structural model

DMF, see Dimethylformamide DM SO, see Dimethyl sulfoxide DMT (dimethoxytrilyl ether), DNA synthesis and, 1114 DNA, see Deoxyribonucleic acid DNA fingerprinting, 1118-1119 reliability of, 1119 STR loci and, 1118 Dopamine, molecular model of. 930 Double bond, electronic structure of, 16... 

Fig. 45. Structural models of adsorbed molecules at Pt(100) and Pt(lll) surfaces, (a) L-Dopa (b) L-Tyrosine (c) L-Cysteine (d) L-Phenylalanine (e) L-Alanine (f) Dopamine (g) Catechol. Reprinted from ref. 84.

These studies provide structural models that should be useful for analyzing the dopamine/dendrimer systems. The next step is to test the effectiveness of these modified materials for encapsulation of dopamine (and related materials) and to determine how effectively they are delivered to the kidney centers. As such experiments proceed, continuing simulation will be useful in providing a quantitative framework for understanding various results. 

To help characterize the structure and function of dopamine receptors at the molecular level, the x-ray crystal structure of apomorphine (77) was compared to a structural model of dopamine ("Fig. 25.9k It is obvious that apomorphine contains molecular features In common with the structure of dopamine In the trans a-rotamer conformation ("Figs. 25.9 and 25. 0). Isoapomorphine, which embeds the structure of dopamine In the trans p-rotamerlc conformation ("Fig. 25.10k Is less active than apomorphine as a dopamine agonist. The... 

Seiler, M.P., Floersheim, P., Markstein, R. and Widmei A. (1993) Structure-activity relationships in the ra s-Hexahydroindolo[4, 3- f>]phenanthridine ( Benzergoline ) series. 2. Resolution, absolute configuration, and dopaminergic activity of the selective Dj agonist CY 208-243 and its implification for an extended rotamer-based dopamine receptor model ./. Med. Chem., 36, 977-984. 

Figure 3. Structural models of adsorbed molecules at Pt(lOO) and Pt(lll) surfaces. (A) L-dopa (LD) (B) L-Tyrosine (TYR) (C) L-cysteine (CYS) (D) L-phenylalanine (PHE) (E) L-alanine (ALA) (F) dopamine (DA) (G) catechol (CT) (H) 3,4-dihydroxyphenyl-acetic acid (DOPAC).

Figure 3 The chemical structures of the ligands used in the molecular modeling study of the Di dopamine receptor. The ligands were divided into two groups (active and inactive) based on their pharmacological properties. The hypothesized pharmacophoric elements are shown in bold.

Varady J, Wu X, Fang X, Min J, Hu Z, Levant B, Wang S. Molecular modeling of the three-dimensional structure of dopamine 3 (D3) subtype receptor discovery of novel and potent D3 ligands through a hybrid pharmacophore-and structure-based database searching approach. / Med Chem 2003 46 4377-92. 

In addition, Zn2+ was shown to inhibit dopamine uptake in a mutant containing an engineered tridentate zinc site, in which the i-4 site from His3757.60, Met3717.56, was replaced with histidine, whereas the introduction of histidines at the i-2, i-3, and i-5 position did not increase Zn2+ affinity (29). In contrast, histidines at positions i+2, i+3, and i+4 all resulted in potent inhibition of dopamine uptake by Zn2+. The incorporation of these data in a model of secondary structure provides evidence for an a-helical configuration of the extracellular portion of TM7, as well as the absence of well-defined secondary structure between positions 3757.6o and 37 97.64 (Fig. IB), thereby suggesting an approximate boundary between the C-terminal end of the helix and the beginning of EL4 (29). 

Tyrosinase is a monooxygenase which catalyzes the incorporation of one oxygen atom from dioxygen into phenols and further oxidizes the catechols formed to o-quinones (oxidase action). A comparison of spectral (EPR, electronic absorption, CD, and resonance Raman) properties of oxy-tyrosinase and its derivatives with those of oxy-Hc establishes a close similarity of the active site structures in these proteins (26-29). Thus, it seems likely that there is a close relationship between the binding of dioxygen and the ability to "activate" it for reaction and incoiporation into organic substrates. Other important copper monooxygenases which are however of lesser relevance to the model studies discussed below include dopamine p-hydroxylase (16,30) and a recently described copper-dependent phenylalanine hydroxylase (31). 

Recent data in our laboratories indicated the possible involvement of central and peripheral dopamine binding sites in the pathogenesis of duodenal ulceration. Structure activity studies with duodenal ulcerogens implicated dopamine as a putative mediator and/or modulator in duodenal ulceration. Using the cysteamine- or propionitrile-induced duodenal ulcer model in rats, we found that dopamine agonists (e.g., bromocriptine, lergotrile,... 

A topographical model has been proposed to explain why (E)-2-(3,4-dihydroxyphenyl)cyclopropylamine, 1, and alpha-methyldopamine (AMDA) are inactive in the renal vascular dopamine (DA) receptor system. In this model a steric protrusion (S2) resides approximately lX above the generalized plane of the receptor and acts to impede interaction with molecules such as 1 and AMDA which possess additional bulk in this region. Recent developments in DA structure-activity relationships offer further support for the existence of the S2 site. 

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