Abstracts


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PKC delta and epsilon in drug targeting and therapeutics
Yonezawa T., Kurata R., Kimura M., Inoko H.

Protein kinase C (PKC) belongs to the serine and threonine kinase family. At least ten PKC isoforms have been identified and subdivided into three groups: classical (alpha, beta I, beta II and gamma), novel (delta, epsilon, theta and eta), and atypical (zeta and iota/lambda). Two calcium-insensitive isoforms of novel PKC, PKC delta and epsilon, have received particular attention as promising targets for new drugs. PKCs play a multifaceted role in cellular responses in a range of tissues. Professor Mochly-Rosen's group and KAI Pharmaceuticals Inc. have developed drugs targeted against PKC delta (KAI-9803) and epsilon (KAI-1678). These drugs ameliorate pathological conditions in acute myocardial infarction and reduce pain via specific modulation of membrane-translocation of PKC delta or epsilon. Another research group has recently used the KinAceTM approach to produce PKC epsilon-abrogating peptides (KCe-12 and KCe-16) that are based on the catalytic domain of PKC. These peptides specifically inhibit PKC epsilon and ameliorate pathological conditions in a rodent insulin resistance model. This review describes the development of these therapeutic drugs targeting PKC delta and epsilon by two independent groups in the light of recent patents.


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Recent patents on antimicrobial peptides
Pathan F.K., Venkata D.A., Panguluri S.K.

Research on antimicrobial peptides has gained pace to exploit their potential and ability to replace conventional antibiotics. Antimicrobial peptides are important members of the host defense system, as they have a broad ability to kill microbes. Antimicrobial peptides and proteins form an important means of host defense in eukaryotes. Large antimicrobial proteins (>100 a.a.), are often lytic, nutrient-binding proteins or specifically target the microbial macromolecules. Small antimicrobial peptides act by disrupting the structure or function of microbial cell membranes. A multitude of antimicrobial peptides has been found in the epithelial layers, phagocytes, and body fluids of multicellular animals including humans. Aside from their role as endogenous antibiotics, antimicrobial peptides have functions in inflammation, wound repair, and regulation of the adaptive immune system. In this review, we discuss recent patents relating to antimicrobial peptides. These patents are related to the method of identifying peptides that have antimicrobial activity, including the papillosin antimicrobial peptide and its encoding gene, the antimicrobial peptide isolated from Halocynthia aurantium, retrocyclins, and the use of cathelicidin LL-37 and its derivatives for wound healing. These patents provide valuable information that could be useful in the identification of antimicrobial peptides and the exploitation of their therapeutic potential.


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Estrogen receptor polymorphisms: Significance to human physiology, disease and therapy
Figtree G.A., Noonan J.E., Bhindi R., Collins P.

Other than its well-recognized effects on reproductive physiology, estrogen has important actions in a wide variety of other body systems with important examples including bone, blood vessels and the heart. These effects are seen in both females and males. Investigators have hypothesized that genetic variants in the genes coding for estrogen signalling proteins may cause variable sensitivity to the hormone and influence an individual's estrogen-sensitive phenotypes. The most obvious candidate genes are the estrogen receptors alpha and beta (ERα and β). However, the regulation of these genes is complex and not well understood. Furthermore, their coding exons, and regulatory sequences are dispersed across large segments of the genome. A number of common polymorphisms have been identified in both ERα and ERβ, with variable degrees of evidence of their direct biological significance and their association with human disease. The identification of genetic variations associated with altered estrogen response is of potential public health importance. Insights may be gained into the pathogenesis of estrogen sensitive diseases such as osteoporosis, breast cancer and cardiovascular disease contributing to the development and application of newer therapies for these disorders. Furthermore, genetic variants that alter sensitivity to estrogen may affect both therapeutic and harmful responses to exogenous estrogen administered in the form of the oral contraceptive pill or hormone replacement therapy. This clinical significance has led to the publication of a number of patents which will be reviewed.


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RNA silencing: Recent developments on miRNAs
Nicolas F.E., Lopez-Gomollon S., Lopez-Martinez A.F., Dalmay T.

MicroRNAs (miRNAs) are small non-protein-coding transcripts that regulate gene expression post-transcriptionally by pairing with target messenger RNAs (mRNAs). It is predicted that humans express thousands of miRNAs and, although only a few hundred have been identified, there is already mounting evidence suggesting that they play an important role in several different developmental processes. It is therefore not surprising that miRNAs have been found to be deregulated in many diseases. The discovery of miRNAs has uncovered a natural form of controlling RNA transcription and translation, which could provide new avenues for diagnosis, prognostic, and therapeutic applications. This review summarizes some of the key recently published patents and relevant research advances on miRNA target identification, strategies to modulate their activity and the potential applications in human diseases such as cancer and viral infections, as well as methods and techniques for purification, detection and quantification of miRNAs.