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9 -{[2 -Hydroxy-I -(hydroxymethyl)ethoxy]methyllguanine (2'-nor-2'-deoxyguanosine; 2'NDG) selectively inhibits the replication of herpes group viruses. In cell culture studies 2'NDG was at least 10-fold more potent than acyclovir (ACV) in inhibition of human cytomegalovirus replication and Epstein-Barr virus-induced lymphocyte transformation and was about as effective as ACV in inhibition of herpes simplex viruses 1 and 2 and varicella zoster virus. Orally administered 2'NDG was 6-to 50-fold more efficacious than ACV in treating systemic or local HSV-1 infection or HSV-2 intravaginal infection in mice. The mode of action of 2'NDG appears to involve phosphorylation by herpes simplex virus thymidine kinase and subsequent phosphorylations by cellular kinases to produce 2'NDG triphosphate, which is a potent inhibitor of herpes virus DNA polymerase. Compared to ACV, 2'NDG was a more efficient substrate for HSV-1 thymidine kinase (Vma./Km for 2'NDG 30-fold higher than that for ACV), whereas 2'NDG monophosphate is a more efficient substrate for GMP kinase (Vm./Km for 2'NDG monophosphate 492-fold higher than that for ACV monophosphate). The combined effect is more rapid production of the inhibitory triphosphate from 2'NDG than from ACV.As part of our studies on the structure-activity relationships of herpes virus encoded thymidine kinase (TK) and DNA polymerase, a nucleoside analog, 9-{[2-hydroxy-1-(hydroxymethyl)-ethoxy]methyl}guanine (2'-nor-2'-deoxyguanosine; 2'NDG) (1-3) was synthesized. 2'NDG is an efficient substrate for the herpes simplex virus 1 (HSV-1) TK and is readily converted to the triphosphate, a potent inhibitor of viral DNA polymerase (1).In the present studies, a chemical synthesis of 2'NDG, the characteristics of its selective phosphorylation by HSV-1 TK, and its rapid conversion to the triphosphate are more fully described. In addition, data are presented demonstrating that the rapid phosphorylation of 2'NDG is correlated with potent inhibition of herpes virus replication in cell cultures and both prophylactic and therapeutic efficacy against herpes virus infections in mice.MATERIALS AND METHODS Materials. Phosphocreatine, creatine kinase, ATP, deoxythymidine, and dGMP were purchased from Sigma; GMP kinase (hog brain) and NADH, from Boehringer Mannheim; lactate dehydrogenase, from Worthington; [methyl-3H] by determining the drug concentration (,ug/ml) required to confer a 50% plaque inhibition on duplicate cell monolayers [for HSV-1, VZV, HCMV, Mengo virus, and vaccinia virus]. For both assays, the antiviral compound was added to the maintenance medium at the time of infection. Viral cytopathic effect was evaluated after incubation for 5 days at 37°C, and plaque development was evaluated after incubation for 3 days (7 days for HCMV) at 370C. Inhibition of EBV replication was measured by prevention of transformation of normal cord lymphocytes to lymphoblastoid cells. In brief, lymphocyte-rich suspensions were prepared from fresh, heparinized human cord blood specimens by differential centrifu...

Synthetic and natural peptides that act as nonselective melanocortin receptor agonists have been found to be anorexigenic and to stimulate erectile activity. We report the design and development of 1, a potent, selective (1184-fold vs MC3R, 350-fold vs MC5R), small-molecule agonist of the MC4 receptor. Pharmacological testing confirms the food intake lowering effects of MC4R agonism and suggests another role for the receptor in the stimulation of erectile activity.

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Cereal Chem. 82(2):187-190 Three different modified dry-grind corn processes, quick germ (QG), quick germ and quick fiber (QGQF), and enzymatic milling (E-Mill) were compared with the conventional dry-grind corn process for fermentation characteristics and distillers dried grains with solubles (DDGS) composition. Significant effects were observed on fermentation characteristics and DDGS composition with these modified dry-grind processes. The QG, QGQF, and E-Mill processes increased ethanol concentration by 8-27% relative to the conventional dry-grind process. These process modifications reduced the fiber content of DDGS from 11 to 2% and increased the protein content of DDGS from 28 to 58%.

An aqueous enzymatic method was developed to extract corn oil from corn germ. The basic steps in the method involved “churning” the corn germ with various enzymes and buffer for 4 h at 50°C, and an additional 16 h at 65°C, followed by centrifugation and removal of the oil layer from the surface. No hexane or other organic solvents are used in this process. By using oven‐dried corn germ samples (6 g) from a commercial corn wet mill, corn oil yields of about 80% were achieved using three different commercial cellulases. A fourfold scale‐up of the method (to 24 g of germ) resulted in oil yields of about 90%. Nine other commercial enzymes were evaluated and resulted in significant but lower oil yields. In the absence of enzymes, oil yields of 27 to 37% were achieved. The chemical compositions of hexane‐extracted vs. aqueous enzymatic‐extracted corn oils were very similar.

Iii CoI1\CIItiOI1I dI\-,,i,J coin pIi)cc.. 'atiJi I CiSi\ Cl cd into LIC\[IIIIIS i,stn liquclactioli entymes at high temperatures (90-120'C) during a liquefaction step. Dextrins are hydrolyzed into sugars using saccliaritication enzymes during a simultaneous sacchartfication and fermentation (SSF) step. Recently, a raw starch hydrolyzing enzyme (RSU), Star-en 001, was developed that converts starch into dextrins at low ternperatures (<48°C) and hydrolyzes dextrins into sugars during SSF. In this study, a dry-grind corn process using RSH enzyme was compared with o combinations (DGI and DG2) of commercial liquefaction and s:,ccharification enzymes. Dry-grind corn processes for all enzyme treat-Department of Agricultural and Biological Engineering, University of Illinois.