Codon usage biases in Alzheimer's disease and other neurodegenerative diseases.

Establishing codon usage biases are crucial for understanding the etiology of central nervous system neurodegenerative diseases (CNSNDD) especially Alzheimer's disease (AD) as well as genetic factors. G and C ending codons are strongly biased in the coding sequences of these proteins as a result of genomic GC composition constraints. On the other hand, codons that identified as translationally optimal in the major trend all end in C or G, suggesting translational selection should also be taken into consideration additional to compositional constraints. Furthermore, this investigation reveals that three common codons, CGC (Arg), AGC (Ser), and GGC (Gly), are also critical in affecting codon usage bias. They not only can offer an insight into the codon usage bias of AD and its mechanism, but also may help in the possible cures for these diseases.

Molecular dynamics of some pentapeptides having a strong tendency to helical conformation.

Some pentapeptides with higher alpha-helical tendency possess typical sequence pattern, such as "+ - + + - - +", "+ - - + - - +", "+ - + - - - +", and " - + + - - - +" ( "+" = D,N,E,Q,K,R,T,C, or H; "-" = L,I,V, or A), especially symmetrical motifs (a pair of reverse sequences beside palindromic segments), such as ALALA, QQAQE/EQAQQ, and REALE/ELAER, hint that the nascent peptide can fold a certain conformation in a two-way folding fashion.

Construction of drug screening cell model and application to new compounds inhibiting FITC-fibrinogen binding to CHO cells expressing human alphaIIbbeta3.

To identify potential candidates for antiplatelet drugs, human alphaIIbbeta3 (GPIIb/IIIa) was expressed in Chinese hamster ovary (CHO) cells, which was validated by tetrapeptide RGDS (Arg-Gly-Asp-Ser) with IC(50) of 0.057 mM, supported by Basani's results [Basani, R. B., French, D. L., Vilaire, G., Brown, D. L., Chen, F., Coller, B. S., Derrick, J. M., Gartner, T. K., Bennett, J. S., Poncz, M., 2000. A naturally occurring mutation near the amino terminus of alpha IIb defines a new region involved in ligand binding to alpha IIbbeta 3. Blood 95, 180-188]. The ability of 2-(4-substituted-piperazin-1-ylacetyl)-1,2,3,4-tetrahydroisoquinoline derivatives to inhibit fibrinogen binding to alphaIIbbeta3 based on the CHO cell model was measured by flow cytometry using GPIIb/IIIa assay, and the IC(50) values of compounds 1-6 were 0.166, 0.037, 0.311, 0.025, 0.034, and 0.184 mM, respectively. Our research results indicated that the compounds with phenylsulfonyl (compounds 1 and 2) and benzoyl groups (compounds 4 and 5) at position 4 of piperazine showed higher IC(50) values of inhibiting ADP-induced human platelet aggregation. Particularly compound 4 possessed IC(50) value of approximately 6.84 nM. Additionally, a complex model of alphaIIbbeta3 with compound 4 revealed that the pharmacophore of compound 4, including m-nitro group of 4-benzene-piperazine, the nitrogen atom in the piperazine group, and 2-nitrogen of 1,2,3,4-tetrahydroisoquinoline nucleus, interacted with the hydroxyl groups of Thr125 of beta3 and Tyr166 of alpha2b by hydrogen bonds and the carboxyl group at side chain of Asp179 of alpha2b in the fashion of electrostatic interaction. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays showed that compounds 4 and 5 possess potential anti-cancer activities, suggesting a potential role of integrin-guided signal pathway in cancer therapy. Further evaluation is under investigation.