Conformationally designed biomimetic systems and the investigation of the conformation control of biological reactions is becoming a topic of active research at the interface of chemistry and biology.[1] In this context the interrelationship between macrocycle conformation and physicochemical properties in porphyrins is emerging as a topic of special biological relevance. Various nonplanar conformations have been observed for the porphyrinoid cofactors involved in photosynthesis, electron transfer and respiration and it is now believed that the physicochemical properties of the natural tetrapyrroles are fine-tuned via steric interactions with the protein skeleton in a conformational control process.[1b,c,2] For example, there is considerable structural heterogeneity in the accessory bacteriochlorophylls of photosynthesis[3] and a conformational asymmetry is one possible explanation for the unidirectonality of the light-induced electron transfer in the photosynthetic reaction center.[4] Similarly different coactor conformations have been observed for and implied in the action of various heme proteins such as respiratory proteins,[5a] cytochromes,[5b] cytochrome P450[5c] and catalases.[5d] Indeed, dynamic conformation changes and redox dependent changes of the porphyrin conformation in proteins have now been established.[6] Different macrocycle conformations have also been described for diverse tetrapyrrole classes like corrins in B12 and F430[7a] and hydroporphyrins[7b] in sulfite and nitrite reductase[7c].[8

Photosynthesis is the most important energy conversion process for life on earth. Thus, many research groups attempt the synthesis of covalently linked porphyrin quinones to mimic the underlying electron transfer processes occurring in the primary step of photosynthesis. In order to study the influence of different acceptor strengths and geometrical parameters on the electron transfer properties a few hundred porphyrin-p-quinones with different bridging and acceptor units were synthesized.[1] In this context we became interested in the synthesis of stabilized porphyrin-o-quinones, which have not been described by other groups.

Until recently, investigations on the glycosylation of amino acids during the Maillard reaction, on the formation of advanced glycation endproducts (AGE) and the postranslational modification of proteins mainly concentrated on the amino acids lysine, arginine, asparagine, serine and threonine whereas the significance of tryptophan remained largely unnoticed. While studying occurrence and relevance of novel tryptophan metabolites in biological systems, our attention on tryptophan glycosylation was attracted by reports on mannosylated tryptophan residues in proteins [1-6]. In this contribution, we describe the characterization and structure elucidation of novel tryptophan glycoconjugates resulting from the chemical condensation of tryptophan and aldohexoses and demonstrate their occurrence in food samples [7]. In addition, we report on the identification of tryptophan-N- and -C-glycoconjugates, namely N1-(b-D-glucopyranosyl-4C1)-L-tryptophan and 2-(a -manno-pyranosyl-1C4)-L-tryptophan, formed enzymatically as novel tryptophan metabolites in plants [8] and man [7].

Synthesis of the title compound,1-(2'-O-methyl-ß-D-ribofuranosyl)-1H-imidazo-[4,5-d]pyridazine- -4,7(5H,6H)-dione (1), is reported. It was synthesized in four steps, starting from Methyl 1-(ß-D-ribofuranosyl)imidazo-4,5-dicarboxylate (2). The 3',5'-hydroxyl groups of 2 was protected with a bis-silylating agent to form 3, which was then methylated to form the corresponding 2'-O-methyl derivative 5. The silyl deprotection of the latter (to form 6), followed by treatment with hydrazine afforded the target nucleoside 1. The reported nucleoside has potentially beneficial applications in biomedicine based on antisense and triple-helical nucleic acid technologies.

Synthesis of the title compound,1-(2'-deoxy-ß-D-ribofuranosyl)-1H-imidazo[4,5-d]pyridazine- -4,7(5H,6H)-dione (1), is reported. It was synthesized in five steps, commencing with methyl 1-(ß-D-ribofuranosyl)imidazo-4,5-dicarboxylate (2). The 3',5'-hydroxyl groups of 2 was protected with a bis-silylating agent to form 3, which was then converted into the corresponding 2'-thionocarbonate derivative 5. The reduction of the latter with tri-n-butyltin hydride (to form 6), followed by silyl deprotection with tetra-n-btylammonium fluoride, afforded 7. Treatment of the latter with hydrazine hydrate yielded the target nucleoside 1.

A model study for a novel approach to the synthesis of 2-carboxyinosines has been described. The synthesis of 9-benzyl-2-carboxyhypoxanthine (I), a model for 2-carboxyinosine, was achieved in 4 steps starting from 1-benzyl-5-nitroimidazole-4-carboxylic acid. Also reported is the synthesis of 9-benzyl-2,2-bis(ethoxycarbonyl)hypoxanthine (II).

(2R,4'R,8'R)-a-Tocopherol (1), the compound with highest vitamin E activity and, therefore, the biologically most valuable tocopherol, plays an important role in feed, food, and pharma industry. Since an economical total synthesis is not feasible up to now, large-scale production by semi-synthesis starts from natural-source material.1 A mixture of a-, b-, g-, and d-tocopherol (1-4) can be obtained from soybean deodorizer distillates (originally a waste stream of soybean processing) by a combination of various physico-chemical purification steps.

Neuropeptide Y (NPY), a 36-mer neuromodulator, binds to the receptors Y1, Y2, Y4 and Y5 with nanomolar affinity. They all belong to the rhodopsin-like G-protein coupled, seven transmembrane helix spanning receptors. In this study, Ala-substituted and centrally truncated NPY analogues were compared with respect to affinity to the Y-receptors. Furthermore, antibodies against the second (E2) and the third (E3) extracellular loop of NPY Y1-, Y2- and Y5-receptor subtypes were raised and affinity to intact cells was tested by immunofluorescence assays. Both methods were applied in order to receive subtype selective tools and to characterise ligand binding. The analogues [A13]-pNPY and [A27]-pNPY showed subtype selectivity for the Y2-receptor. Sera against the E2 loop of the Y1-receptor and against the E2 loop of the Y2-receptor were subtype selective. Two antibodies against the Y5 E2 and E3 loop recognised the Y5- and Y2-receptor subtypes. In combination, these sera are able to distinguish between the Y1-, Y2-, and Y5-receptor subtypes. The analogues and antibodies represent valuable tools to distinguish NPY receptors on membranes and intact cells.

The characteristics and application of recombinant sucrose synthase 1 (SuSy1) from potato for the synthesis of sucrose analogues are described. With UDP-Glc as donor substrate SuSy1 accepts a variety of ketoses, e.g. 1-deoxy-1-fluoro-D-fructose (100%), D-psicose (7%), L-sorbose (18%) and D-xylulose (7%), as well as aldoses, e.g. D-lyxose (22%) and L-mannose (16%). The enzyme also shows a flexible the donor substrate spectrum with acceptance of UDP-GlcNAc (100%), UDP-GlcA (32%), UDP-Gal (23%), UDP-GalNAc (6%) and UDP-Xyl (39%). The kinetic analysis revealed a substrate inhibition by UDP-Glc with a Km- and KiS-value of 0.46 mM and 2.25 mM, respectively and a Vmax of 21.76 U/mg. A substrate inhibition was also obtained for D-fructose with a Km- and a KiS-value of 2.05 mM and 35.88 mM, respectively, and a Vmax of 10.63 U/mg at a constant concentration of 2 mM UDP-Glc. Susy1 was used for the preparative synthesis of 1´-deoxy-1´-fluoro- b-Dfructofuranosyl- a-D-glucopyranoside and [13C1]-b-D-fructofuranosyl-a-D-glucopyranoside. Both products were characterized by 1H-, 13CNMR and in case of of 1´-deoxy-1´-fluoro-b-D-fructofuranosyl-a-D-glucopyranoside also with 19F-NMR.

Activation parameters [DG200, DH2, DS2] for barriers to rotation about N2O bonds in N-isopropoxypyridine-2(1H)-thione (1) and two 4-substituted N-isopropoxythiazole-2(3H)-thiones 2 and 3 were determined by variable-temperature 1H (600 MHz) and 13C (150 MHz) NMR spectroscopy in the temperature range of T = 135-250 K. The barriers to rotation about N2O bonds in cyclic thiohydroxamic acid O-esters 1, 2, and 3 are explained by a superposition of steric and electronic effects.