抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Signaling Recognition Events with Fluorescent Sensors and Switches.

In the last 10 years the field of molecular diagnostics has witnessed an explosion of interest in the use of nanomaterials in assays for gases, metal ions, and DNA and protein markers for many diseases. Intense research has been fueled by the need for practical, robust, and highly sensitive and selective detection agents that can address the deficiencies of conventional technologies. Chemists are playing an important role in designing and fabricating new materials for application in diagnostic assays. In certain cases assays based upon nanomaterials have offered significant advantages over conventional diagnostic systems with regard to assay sensitivity, selectivity, and practicality. Some of these new methods have recently been reviewed elsewhere with a focus on the materials themselves or as subclassifications in more generalized overviews of biological applications of nanomaterials.1-7 We intend to review some of the major advances and milestones in the field of detection systems based upon nanomaterials and their roles in biodiagnostic screening for nucleic acids, * To whom correspondence should be addressed. Phone: 847-4913907. Fax: 847-467-5123. E-mail: chadnano@northwestern.edu. Nathaniel L. Rosi earned his B.A. degree at Grinnell College (1999) and his Ph.D. degree from the University of Michigan (2003), where he studied the design, synthesis, and gas storage applications of metal−organic frameworks under the guidance of Professor Omar M. Yaghi. In 2003 he began postdoctoral studies as a member of Professor Mirkin’s group at Northwestern University. His current research focuses on the rational assembly of DNA-modified nanostructures into larger-scale materials.

/pdf/nanostructures-in-biodiagnostics-5553cs9yqw.pdf

Nanostructures in Biodiagnostics

Detection of chemical and biological agents plays a fundamental role in biomedical, forensic and environmental sciences1–4 as well as in anti bioterrorism applications.5–7 The development of highly sensitive, cost effective, miniature sensors is therefore in high demand which requires advanced technology coupled with fundamental knowledge in chemistry, biology and material sciences.8–13

In general, sensors feature two functional components: a recognition element to provide selective/specific binding with the target analytes and a transducer component for signaling the binding event. An efficient sensor relies heavily on these two essential components for the recognition process in terms of response time, signal to noise (S/N) ratio, selectivity and limits of detection (LOD).14,15 Therefore, designing sensors with higher efficacy depends on the development of novel materials to improve both the recognition and transduction processes. Nanomaterials feature unique physicochemical properties that can be of great utility in creating new recognition and transduction processes for chemical and biological sensors15–27 as well as improving the S/N ratio by miniaturization of the sensor elements.28

Gold nanoparticles (AuNPs) possess distinct physical and chemical attributes that make them excellent scaffolds for the fabrication of novel chemical and biological sensors (Figure 1).29–36 First, AuNPs can be synthesized in a straightforward manner and can be made highly stable. Second, they possess unique optoelectronic properties. Third, they provide high surface-to-volume ratio with excellent biocompatibility using appropriate ligands.30 Fourth, these properties of AuNPs can be readily tuned varying their size, shape and the surrounding chemical environment. For example, the binding event between recognition element and the analyte can alter physicochemical properties of transducer AuNPs, such as plasmon resonance absorption, conductivity, redox behavior, etc. that in turn can generate a detectable response signal. Finally, AuNPs offer a suitable platform for multi-functionalization with a wide range of organic or biological ligands for the selective binding and detection of small molecules and biological targets.30–32,36 Each of these attributes of AuNPs has allowed researchers to develop novel sensing strategies with improved sensitivity, stability and selectivity. In the last decade of research, the advent of AuNP as a sensory element provided us a broad spectrum of innovative approaches for the detection of metal ions, small molecules, proteins, nucleic acids, malignant cells, etc. in a rapid and efficient manner.37



Figure 1

Physical properties of AuNPs and schematic illustration of an AuNP-based detection system.



In this current review, we have highlighted the several synthetic routes and properties of AuNPs that make them excellent probes for different sensing strategies. Furthermore, we will discuss various sensing strategies and major advances in the last two decades of research utilizing AuNPs in the detection of variety of target analytes including metal ions, organic molecules, proteins, nucleic acids, and microorganisms.

/pdf/gold-nanoparticles-in-chemical-and-biological-sensing-5e2qojkdzn.pdf

Gold nanoparticles in chemical and biological sensing.

I read this book the same weekend that the Packers took on the Rams, and the experience of the latter event, obviously, colored my judgment. Although I abhor anything that smacks of being a handbook (like, \"How to Earn a Merit Badge in Neurosurgery\") because too many volumes in biomedical science already evince a boyscout-like approach, I must confess that parts of this volume are fast, scholarly, and significant, with certain reservations. I like parts of this well-illustrated book because Dr. Sj6strand, without so stating, develops certain subjects on technique in relation to the acquisition of judgment and sophistication. And this is important! So, given that the author (like all of us) is somewhat deficient in some areas, and biased in others, the book is still valuable if the uninitiated reader swallows it in a general fashion, realizing full well that what will be required from the reader is a modulation to fit his vision, propreception, adaptation and response, and the kind of problem he is undertaking. A major deficiency of this book is revealed by comparison of its use of physics and of chemistry to provide understanding and background for the application of high resolution electron microscopy to problems in biology. Since the volume is keyed to high resolution electron microscopy, which is a sophisticated form of structural analysis, but really morphology in a modern guise, the physical and mechanical background of The instrument and its ancillary tools are simply and well presented. The potential use of chemical or cytochemical information as it relates to biological fine structure , however, is quite deficient. I wonder when even sophisticated morphol-ogists will consider fixation a reaction and not a technique; only then will the fundamentals become self-evident and predictable and this sine qua flon will become less mystical. Staining reactions (the most inadequate chapter) ought to be something more than a technique to selectively enhance contrast of morphological elements; it ought to give the structural addresses of some of the chemical residents of cell components. Is it pertinent that auto-radiography gets singled out for more complete coverage than other significant aspects of cytochemistry by a high resolution microscopist, when it has a built-in minimal error of 1,000 A in standard practice? I don't mean to blind-side (in strict football terminology) Dr. Sj6strand's efforts for what is \"routinely used in our laboratory\"; what is done is usually well done. It's just that …

Methods in Enzymology.

Electrochemistry-based sensors offer sensitivity, selectivity and low cost for the detection of selected DNA sequences or mutated genes associated with human disease. DNA-based electrochemical sensors exploit a range of different chemistries, but all take advantage of nanoscale interactions between the target in solution, the recognition layer and a solid electrode surface. Numerous approaches to electrochemical detection have been developed, including direct electrochemistry of DNA, electrochemistry at polymer-modified electrodes, electrochemistry of DNA-specific redox reporters, electrochemical amplifications with nanoparticles, and electrochemical devices based on DNA-mediated charge transport chemistry.

/pdf/electrochemical-dna-sensors-4ft4krws65.pdf

Electrochemical DNA sensors

The design of small complexes that bind and react at specific sequences of DNA becomes important as we begin to delineate, on a molecular level, how genetic information is expressed. A more complete understanding of how to target DNA sites with specificity will lead not only to novel chemotherapeutics but also to a greatly expanded ability for chemists to probe DNA and to develop highly sensitive diagnostic agents.

Recognition and reaction of metallointercalators with DNA.

Mixed-ligand complexes of ruthenium(II): factors governing binding to DNA

Considerable research has focused on the development of nonradioactive probes for nucleic acids. Extensive photophysical studies indicate that Ru(phen){sub 3}{sup 2+} bound to double-helical DNA displays an increase in luminescence owing to intercalation; emission from the metal-to-ligand charge transfer (MLCT) excited state decays as a biexponential with one lifetime of 2 {mu}s attributed to the intercalative form and a second lifetime of 0.6 {mu}s (indistinguishable from the free species) assigned to the surface bound form. Here we report the application of a novel transition-metal complex as a true molecular light switch for DNA. This probe is Ru(bpy){sub 2}(dppz){sup 2+} (bpy = 2,2{prime}-bipyridine, dppz = dipyrido(3,2-a:2{prime},3{prime}-c)phenazine), which shows no photoluminescence in aqueous solution at ambient temperatures, but displays intense photoluminescence in the presence of double-helical DNA, to which the complex binds avidly.

Molecular light switch for DNA : Ru(bpy)2(dppz)2+

Rapid photoinduced electron transfer is demonstrated over a distance of greater than 40 angstroms between metallointercalators that are tethered to the 5' termini of a 15-base pair DNA duplex. An oligomeric assembly was synthesized in which the donor is Ru(phen)2dppz2+ (phen, phenanthroline, and dppz, dipyridophenazine) and the acceptor is Rh(phi)2phen3+ (phi, phenanthrenequinone diimine). These metal complexes are intercalated either one or two base steps in from the helix termini. Although the ruthenium-modified oligonucleotide hybridized to an unmodified complement luminesces intensely, the ruthenium-modified oligomer hybridized to the rhodium-modified oligomer shows no detectable luminescence. Time-resolved studies point to a lower limit of 10(9) per second for the quenching rate. No quenching was observed upon metallation of two complementary octamers by Ru(phen)3(2+) and Rh(phen)3(3+) under conditions where the phen complexes do not intercalate. The stacked aromatic heterocycles of the DNA duplex therefore serve as an efficient medium for coupling electron donors and acceptors over very long distances.

https://science.sciencemag.org/content/sci/262/5136/1025.full.pdf

Jacqueline K. Barton

Papers

Electrochemical DNA sensors

Recognition and reaction of metallointercalators with DNA.

Mixed-ligand complexes of ruthenium(II): factors governing binding to DNA

Molecular light switch for DNA : Ru(bpy)2(dppz)2+

Long-range photoinduced electron transfer through a DNA helix