Current Protein and Peptide Science - Volume 11, Issue 4, 2010

Cyclodextrins are oligosaccharides, specifically cyclic α-1,4-D-glucose oligomers, that possess a cone-like shape resulting in a hydrophobic inner cavity capable of forming complexes with several guest molecules in a hydrophilic matrix. This capability has led to an extensive investigation into cyclodextrin applications in several different substrates with the purpose of overcoming limitations, such as solubility issues, physical degradation and sensitivity to solvents, in guest substances. Researchers have recently described successful interactions between cyclodextrins and proteins, such as enzymes, peptides and amino acids. These complex biomolecules consist of potent active ingredients and are employed in several industrial biocatalyst processes. However, this group in particular tends to have limited usage in pharmaceuticals due to its natural processes of degradation and instability in unusual environments, frequently requiring accurate procedures and stabilization methods in all stages of production. In several cases, the final product still has a short shelflife and often requires a controlled environment for storage. The formation of a cyclodextrin supramolecular complex could not only prevent such problems, but also enhance the intrinsic characteristics of guest substances, thus allowing for an expansion in their industrial production and application. This work focuses on cyclodextrin interactions with proteinlike structures in order to describe their possible applications in the formulation of pharmaceutical proteins.

Antimicrobial peptides (AMPs) are produced by a wide range of organisms and serve as their natural defenses against infection caused by bacteria, viruses and fungi. Because of the positively charge and amphipathic structure, AMPs kill target cells through diverse and complex mechanisms once in a target membrane and these special mechanisms are considered to be the critical factors for the less tendency of drug resistence development. Thus AMPs may become a new generation of promising antimicrobial agents in future anti-infection application. Additionally, AMPs can also be used in food industry and agriculture. On the basis of discussing the structural features, action mechanisms and sources, the applications of AMPs were reviewed in this paper, including in food industry, feedstuff, cultivation of disease-resistant transgenic plant, cultivation of transgenic animal, and aquaculture, especially the patented applications.

Transcriptional repressors and activators are principal control elements in bacterial gene expression. They are involved in the regulation of metabolic pathways, cell division, response to environmental signals, sporulation, replication, to name only a few. Whereas the discovery of these regulators was often fortuitous, a number of molecular, biochemical and biophysical methods have been established that allow to investigate these proteins in great detail and to help understand their functions in the living cell. In this review we focus on a selected set of well characterized transcriptional regulators from Bacillus subtilis and their analysis by methods like EMSA, DNase I footprinting, chemical interference footprinting, in vitro transcription, SELEX, CD measurements, FRET and determination of three-dimensional structure.

Mitochondrial oxidative phosphorylation deficiency is accompanied by various down-stream, adaptive responses which play a key role in the varied phenotypes observed when mitochondrial dysfunction occurs. These responses are often accompanied by the induction of genes involved in defense mechanisms against oxidative stress. Among these responses, metallothioneins (MTs) has been identified to be responsive to mitochondrial dysfunction. MTs, which are expressed in four different isoforms, are small, cysteine rich, metal binding proteins that have been associated with a protective effect in cells under numerous diseased and stressed states. Their diverse functionality and protective roles can be ascribed to their three basic abilities or primary functions which are metal homeostasis, heavy metal detoxification and free radical scavenging. The involvement of MTs with numerous cellular processes, organelles and cells has received much attention while notice of their involvement with the function of mitochondria has been lacking. It is believed that MTs promote the survival of mitochondrial dysfunctional cells by acting as highly efficient reducing elements against the damaging properties of reactive oxygen species (ROS) and by limiting apoptosis. In addition to their role in mitochondrial disease, convincing evidence exist, albeit with conflicting results, of its involvement in some key functions of the mitochondrion, including redox modulation, metal homeostasis and enzyme and transcription factor regulation.

Incorporation of nonnatural amino acids into proteins has exerted great effects on many fields. In recent years, the engineering of translation apparatus facilitates the boom of this field. The modifications on tRNAs, tRNA synthetases, ribosomes, elongation factors and release factors efficiently broaden the repertoire of amino acids and largely increase the efficiency of incorporation. In addition, deep understanding of the translation mechanism helps us generate certain kinds of RNAs which can act as alternative translation components to catalyze the aminoacylation step or inhibitors to attenuate the activity of a certain component. Here I review the strategies to evolve or engineer the components of translation apparatus as well as the methods to control their activity to meet our needs.