Computational survey of FHIT, a putative human tumor suppressor, truncates structure

Fragile Histidine Triad protein [FHIT], as a known tumor suppressor protein, has been proposed to play crucial role in inhibiting p53 degradation by MDM2. Studies have confirmed FHIT interaction with p53 or MDM2, although functional interacting domains of FHIT with MDM2 and/or p53 are not completely defined. Thus, through determining the significant structural interacting domains of FHIT, information with regard to MDM2 and p53 would be provided. As there were no previous studies evaluating the interaction of optimized important parts of target molecules, docking study was employed. Truncated structures of FHIT were screened to reveal critical sections engaging in FHIT interaction. HEX program was used in order to study the interaction of target structures. Given the total energy, FHIT structures [beta5-7, alpha1] and [alpha1] of FHIT were showed to be better candidates in comparison with other structures in interaction with optimized MDM2 part. Furthermore, FHIT structures [beta4-7, alpha1] and [beta5-7, alpha1] were considered to be better than other structures in interaction with optimized p53 part. FHIT truncates which interact with MDM2 optimized part exhibited lower energy levels than FHIT truncates which interact with p53 optimized part. Our results can be useful for designing new inhibitors of this protein complex interaction which would result in tumor repression

Separation of tramadol enantiomers by capillary electrophoresis using highly sulfated cyclodextrins

In the pharmaceutical industry a continuing need for chiral resolution of drugs for various purposes and in diverse matrices exist. For these reasons, analysts may require a number of different separation systems capable of resolving a given pair of enantiomers. Highly sulfated cyclodextrins [HS-CDs] represent a relatively new class of chiral selectors in capillary electrophoresis [CE]. In this investigation the use of HS-CDs as chiral selectors in CE for enantioseparation of tramadol, a highly potent analgesic, as the model drug and the influence of the type of selector and its concentration on enantiomeric resolution were studied. All of the available HSCDs [alpha,beta and gamma] could resolve tramadol enantiomers, but HS-gamma-CD showed better resolution and a baseline resolution was achieved with this selector even at a concentration as low as 0.5% w/v. Additionally, effect of the buffer pH on the enantioresolution was studied. At low pH buffers, in which electroosmotic flow is low in CE, the negatively charged selector prevented the cationic tramadol to migrate out of the capillary even after a long analysis time of 60 minutes. However, at higher pH values [pH=7 or more], the electroosmotic flow is high enough to drag drug-selector complex toward the detector and a reasonable of the enantiomers of the drug was achieved