Decoding the Geography of Natural TBEV Microfoci in Germany: A Geostatistical Approach Based on Land-Use Patterns and Climatological Conditions.

Tickborne-encephalitis (TBE) is a potentially life-threating neurological disease that is mainly transmitted by ticks. The goal of the present study is to analyze the potential uniform environmental patterns of the identified TBEV microfoci in Germany. The results are used to calculate probabilities for the present distribution of TBEV microfoci in Germany based on a geostatistical model.

On-resin Diels-Alder reaction with inverse electron demand: an efficient ligation method for complex peptides with a varying spacer to optimize cell adhesion.

Solid phase peptide synthesis (SPPS) is the method of choice to produce peptides. Several protecting groups enable specific modifications. However, complex peptide conjugates usually require a rather demanding conjugation strategy, which is mostly performed in solution.

Multifunctional Coating Improves Cell Adhesion on Titanium by using Cooperatively Acting Peptides.

Promotion of cell adhesion on biomaterials is crucial for the long-term success of a titanium implant. Herein a novel concept is highlighted combining very stable and affine titanium surface adhesive properties with specific cell binding moieties in one molecule. A peptide containing L-3,4-dihydroxyphenylalanine was synthesized and affinity to titanium was investigated.

NIR-Cyanine Dye Linker: a Promising Candidate for Isochronic Fluorescence Imaging in Molecular Cancer Diagnostics and Therapy Monitoring.

Personalized anti-cancer medicine is boosted by the recent development of molecular diagnostics and molecularly targeted drugs requiring rapid and efficient ligation routes. Here, we present a novel approach to synthetize a conjugate able to act simultaneously as an imaging and as a chemotherapeutic agent by coupling functional peptides employing solid phase peptide synthesis technologies. Development and the first synthesis of a fluorescent dye with similarity in the polymethine part of the Cy7 molecule whose indolenine-N residues were substituted with a propylene linker are described.

A peptide & peptide nucleic acid synthesis technology for transporter molecules and theranostics--the SPPS.

Advances in imaging diagnostics using magnetic resonance tomography (MRT), positron emission tomography (PET) and fluorescence imaging including near infrared (NIR) imaging methods are facilitated by constant improvement of the concepts of peptide synthesis. Feasible patient-specific theranostic platforms in the personalized medicine are particularly dependent on efficient and clinically applicable peptide constructs. The role of peptides in the interrelations between the structure and function of proteins is widely investigated, especially by using computer-assisted methods.

Spatial localization of genes determined by intranuclear DNA fragmentation with the fusion proteins lamin KRED and histone KRED und visible light.

The highly organized DNA architecture inside of the nuclei of cells is accepted in the scientific world. In the human genome about 3 billion nucleotides are organized as chromatin in the cell nucleus. In general, they are involved in gene regulation and transcription by histone modification.

SPPS resins impact the PNA-syntheses' improvement.

The personalized medicine, also documented as "individualized medicine", is an effective and therapeutic approach. It is designed to treat the disease of the individual patient whose precise differential gene expression profile is well known. The trend in the biomedical and biophysical research shows important consequences for the pharmaceutical drug and diagnostics research.

Biocompatible silicon surfaces through orthogonal click chemistries and a high affinity silicon oxide binding peptide.

Multifunctionality is gaining more and more importance in the field of improved biomaterials. Especially peptides feature a broad chemical variability and are versatile mediators between inorganic surfaces and living cells. Here, we synthesized a unique peptide that binds to SiO(2) with nM affinity.

BioShuttle mobility in living cells studied with high-resolution FCS & CLSM methodologies.

With the increase in molecular diagnostics and patient-specific therapeutic approaches, the delivery and targeting of imaging molecules and pharmacologically active agents gain increasing importance. The ideal delivery system does not exist yet. The realization of two features is indispensable: first, a locally high concentration of target-specific diagnostic and therapeutic molecules; second, the broad development of effective and safe carrier systems.

ROS-mediated killing efficiency with visible light of bacteria carrying different red fluorochrome proteins.

Red fluorescent proteins can generate reactive oxygen species (ROS) if their fluorochrome is stimulated e.g. by visible light illumination.

Theranostic cRGD-BioShuttle Constructs Containing Temozolomide- and Cy7 For NIR-Imaging and Therapy.

Innovative and personalized therapeutic approaches result from the identification and control of individual aberrantly expressed genes at the transcriptional and post-transcriptional level. Therefore, it is of high interest to establish diagnostic, therapeutic and theranostic strategies at these levels. In the present study, we used the Diels-Alder Reaction with inverse electron demand (DAR(inv)) click chemistry to prepare a series of cyclic RGD-BioShuttle constructs.

Improved synthesis strategy for peptide nucleic acids (PNA) appropriate for cell-specific fluorescence imaging.

Progress in genomics and proteomics attended to the door for better understanding the recent rapid expanding complex research field of metabolomics. This trend in biomedical research increasingly focuses to the development of patient-specific therapeutic approaches with higher efficiency and sustainability. Simultaneously undesired adverse reactions are avoided.

Enhancement of the click chemistry for the inverse Diels Alder technology by functionalization of amide-based monomers.

In the near future personalized medicine with nucleic acids will play a key role in molecular diagnostics and therapy, which require new properties of the nucleic acids, like stability against enzymatic degradation. Here we demonstrate that the replacement of nucleobases with PNA by functional molecules harbouring either a dienophile or a diene reactivity is feasible and confers all new options for functionalization. These newly developed derivatives allow independent multi-ligations of multi-faceted components by use of the inverse Diels Alder technology.

Positioning effects of KillerRed inside of cells correlate with DNA strand breaks after activation with visible light.

Fluorescent proteins (FPs) are established tools for new applications, not-restricted to the cell biological research. They could also be ideal in surgery enhancing the precision to differentiate between the target tissue and the surrounding healthy tissue. FPs like the KillerRed (KRED), used here, can be activated by excitation with visible day-light for emitting active electrons which produce reactive oxygen species (ROS) resulting in photokilling processes.

A cyclic-RGD-BioShuttle functionalized with TMZ by DARinv "Click Chemistry" targeted to αvβ3 integrin for therapy.

Clinical experiences often document, that a successful tumor control requires high doses of drug applications. It is widely believed that unavoidable adverse reactions could be minimized by using gene-therapeutic strategies protecting the tumor-surrounding healthy tissue as well as the bone-marrow. One new approach in this direction is the use of "Targeted Therapies" realizing a selective drug targeting to gain effectual amounts at the target site, even with drastically reduced application doses.

Extension of the PNA world by functionalized PNA monomers eligible candidates for inverse Diels Alder Click Chemistry.

Progress in genome research led to new perspectives in diagnostic applications and to new promising therapies. On account of their specificity and sensitivity, nucleic acids (DNA/RNA) increasingly are in the focus of the scientific interest. While nucleic acids were a target of therapeutic interventions up to now, they could serve as excellent tools in the future, being highly sequence-specific in molecular diagnostics.

Gain of a 500-fold sensitivity on an intravital MR contrast agent based on an endohedral gadolinium-cluster-fullerene-conjugate: a new chance in cancer diagnostics.

Among the applications of fullerene technology in health sciences the expanding field of magnetic resonance imaging (MRI) of molecular processes is most challenging. Here we present the synthesis and application of a Gd(x)Sc(3-x)N@C(80)-BioShuttle-conjugate referred to as Gd-cluster@-BioShuttle, which features high proton relaxation and, in comparison to the commonly used contrast agents, high signal enhancement at very low Gd concentrations. This modularly designed contrast agent represents a new tool for improved monitoring and evaluation of interventions at the gene transcription level.

The Diels-Alder-reaction with inverse-electron-demand, a very efficient versatile click-reaction concept for proper ligation of variable molecular partners.

The ligation of active pharmaceutical ingredients (API) for working with image processing systems in diagnostics (MRT) attracts increasing notice and scientific interest. The Diels-Alder ligation Reaction with inverse electron demand (DAR(inv)) turns out to be an appropriate candidate. The DAR(inv) is characterized by a specific distribution of electrons of the diene and the corresponding dienophile counterpart.

From green to red--To more dead? Autofluorescent proteins as photosensitizers.

Inactive compounds like autofluorescent proteins can absorb visible daylight (around 500-700 nm) and can emit active electrons producing reactive oxygen species (ROS) leading to an increase in photokilling processes in bacteria. The endogenously originated ROS create single strand breaks in the cells DNA. These various types of breaks can be partially repaired by different cellular repair systems but a high number of breaks leads to cell death.

Autofluorescent proteins as photosensitizer in eukaryontes.

Since the discovery of the green fluorescent green protein (GFP) in 1961 many variants of fluorescent proteins (FP) were detected. The importance was underlined by the Nobel price award in chemistry 2008 for the invention, application, and development of the GFP by Shimomura, Chalfie and Tsien. GFP, first described by Shimomura now is indispensible in the scientific daily life.

High-resolution flow cytometry: a suitable tool for monitoring aneuploid prostate cancer cells after TMZ and TMZ-BioShuttle treatment.

If metastatic prostate cancer gets resistant to antiandrogen therapy, there are few treatment options, because prostate cancer is not very sensitive to cytostatic agents. Temozolomide (TMZ) as an orally applicable chemotherapeutic substance has been proven to be effective and well tolerated with occasional moderate toxicity especially for brain tumors and an application to prostate cancer cells seemed to be promising. Unfortunately, TMZ was inefficient in the treatment of symptomatic progressive hormone-refractory prostate cancer (HRPC).

Treatment of glioblastoma multiforme cells with temozolomide-BioShuttle ligated by the inverse Diels-Alder ligation chemistry.

Recurrent glioblastoma multiforme (GBM), insensitive against most therapeutic interventions, has low response and survival rates. Temozolomide (TMZ) was approved for second-line therapy of recurrent anaplastic astrocytoma. However, TMZ therapy in GBM patients reveals properties such as reduced tolerability and inauspicious hemogram.

Transporter molecules influence the gene expression in HeLa cells.

Progresses in biology and pharmacology led to highly specific bioactive substances, but their poor bioavailability at the site of action is a result of their physico-chemical properties. Various design approaches for transport carrier molecules facilitating the cellular entry of bioactive substances could help to reach their molecular target in cells and tissues. The transfer efficacy and the subsequent pharmacological effects of the cargo molecules are well investigated, but the investigations of effects of the carrier molecules themselves on the target cells or tissues remain necessary.