Rabbit Anti-Human COMT (a.a. 52-271) Polyclonal antibody

Nicotinamide N-methyltransferase (NNMT) catalyzes the methylation of nicotinamide to form N-methylnicotinamide. Overexpression of NNMT is associated with a variety of diseases, including a number of cancers and metabolic disorders, suggesting a role for NNMT as a potential therapeutic target. By structural modification of a lead NNMT inhibitor previously developed in our group, we prepared a diverse library of inhibitors to probe the different regions of the enzymes active site. This investigation revealed that incorporation of a naphthalene moiety, intended to bind the hydrophobic nicotinamide binding pocket via pi-pi stacking interactions, significantly increases the activity of bisubstrate-like NNMT inhibitors (half-maximal inhibitory concentration 1.41 mu M). These findings are further supported by isothermal titration calorimetry binding assays as well as modeling studies. The most active NNMT inhibitor identified in the present study demonstrated a dose-dependent inhibitory effect on the cell proliferation of the HSC-2 human oral cancer cell line.

Background:Impaired dopamine metabolism is associated with Parkinson's disease (PD). Considering the overlap in the clinical and pathological characteristics between PD and multiple system atrophy (MSA), we investigated the effect of five potential functional polymorphisms in dopamine metabolism-related genes on disease susceptibility, phenotypes, and responses to dopamine in a large sample of PD and MSA patients. Methods:A total of 1506 PD patients, 496 MSA patients, and 894 healthy controls were included in this study. Five variants (rs6356 inTH, rs921451 inDDC, rs4680 inCOMT, rs1799836 inMAOB, and rs1611115 inDBH) were genotyped in all cases using Sequenom iPLEX Assay technology. Results:After adjusting for gender and age at onset, except forDDCrs921451, which was associated with an increased risk of MSA (p= 0.001, OR = 1.21), no significant differences were found in genotype distribution or minor allele frequencies for the other four variants between PD and MSA patients and healthy controls. In the subgroup analysis,DDCrs921451 was associated with an increased risk for late-onset PD as well as for PD onset in males (p= 0.002 [OR = 1.13]p= 0.003 [OR = 1.15], respectively). In addition, patients harboring the risk alleleDDCrs921451 required lower levodopa equivalent daily doses of dopaminergic medication than those without the risk allele (52.00 +/- 21.31 mg/day,p= 0.015). Conclusion:None of the five candidate functional variants is a major determinant of the risk for PD or MSA. The modified PD phenotypes associated with these variants requires further confirmation.