BINDing molecules

Mouse μ-opioid receptor carboxy-terminal splice variants have been shown to differ in their responses to agonists.     

Interstellar molecules

Summary The study of interstellar molecules broadly includes two areas of interest. One area uses the unique ability of molecules to act as probes of the physical conditions in the cold, dense, visually opaque component of the interstellar medium. The physical properties of this and other components of the interstellar medium are summarized. The other area deals with the chemistry of interstellar molecules, recent aspects of which are emphasized in this review. Gas-phase chemistry, shock chemistry, and grain surface chemistry are discussed in the context of recent observations. No present observations suggest that surface reactions are relevant, but neither can they be ruled out. Ion-molecule reactions are clearly operative, at least for the simpler species. Chemical isotope fractionation is reviewed, andd it is concluded that the complexities of the chemistry allow no cosmological conclusions to be drawn from observations of deuterium in interstellar molecules, while the presence of¹³C in interstellar molecules permits an estimate of the¹²C/¹³C ratio which is consistent with the current concepts of the nucleosynthesis history of the Galaxy. Possible connections between interstellar molecules and the early molecular history of the solar system are discussed.This is the first of a series of papers which will appear in the Synthesis section of the Journal of Molecular Evolution pertaining to the topic Organic Molecules in the Solar System and Beyond.Operated by Associated Universitites, Inc., under contract with the National Science Foundation     

Mind molecules

Scientific styles vary tremendously. For me, research is largely about the unfettered pursuit of novel ideas and experiments that can test multiple ideas in a day, not a year, an approach that I learned from my mentor Julius "Julie" Axelrod. This focus on creative conceptualizations has been my métier since working in the summers during medical school at the National Institutes of Health, during my two years in the Axelrod laboratory, and throughout my forty-five years at Johns Hopkins University School of Medicine. Equally important has been the "high" that emerges from brainstorming with my students. Nothing can compare with the eureka moments when, together, we sense new insights and, better yet, when high-risk, high-payoff experiments succeed. Although I have studied many different questions over the years, a common theme emerges: simple biochemical approaches to understanding molecular messengers, usually small molecules. Equally important has been identifying, purifying, and cloning the messengers' relevant biosynthetic, degradative, or target proteins, at all times seeking potential therapeutic relevance in the form of drugs. In the interests of brevity, this Reflections article is highly selective, and, with a few exceptions, literature citations are only of findings of our laboratory that illustrate notable themes.     

'Escentric' molecules

Can a fragrance be revolutionary? In this commentary, the creation of two unusual, extravagant fine fragrances, ‘escentr?c01’ and ‘molecule01’, is described. In response to the fantasy components found in release notes of many recent perfume launches, both center around a single real fragrance raw material, the transparent woody aroma chemical ‘Iso E Super’ ( 1 + 2 ). The perfume ‘escentr?c01’ contains 65% of it, accompanied by Trisamber ( 3 ), red pepper, lime oil, incense and musks, while ‘molecule01’ consists exclusively of ‘Iso E Super’ ( 1 + 2 ). The elegant woody note lives here its own eccentric life – the revolution starts.     

The molecules of memory

Identifying the key components in the molecular mechanisms of learning and memory is a highly complex process. Here we look at some specific experimental research that has contributed to our knowledge of molecular memory.     

Biophysics of single molecules

The modern methods of research on biological molecules which have led to the development of a new field of science, biophysics of single molecules, are reviewed. The measurement of the characteristics of single molecules enables one to reveal their individual features, and it is just for this reason that much more information can be obtained from one molecule than from the entire ensemble of molecules. The high sensitivity of the methods considered in detail makes it possible to come close to solving the basic problem of practical importance, namely, the determination of the nucleotide sequence of a single DNA molecule.     

Alignment of chain-like molecules

The steric obstruction model, that describes the enhanced alignment of folded proteins by anisotropic medium, is extended to account for the residual dipolar couplings of chain-like polypeptides. The average alignment of each chain segment is calculated from an ensemble of conformations represented by a spatial probability distribution. The segmental alignment depends on chain length, flexibility and segment's position in the chain. Residual dipolar couplings in turn depend on internuclear vector directions within each fragment. The results of calculations and simulations explain salient features of the experimental data. With this insight residual dipolar couplings can be interpreted to assess the degree of denaturation, local structures and spatial organization of weakly structured proteins.     

Sensing cell-secreted molecules

Fields of medicine and life sciences are constantly evolving and striving for improved understanding of how cells function at an individual level, small ensemble level, and tissue level. Such improved understanding will translate into developing therapeutic strategies as well as approaches for disease diagnosis. Behavior of cells at all levels is shaped in significant part by secreted molecules that serve as cues for proliferation, migration, death, and other cell life-altering events. Improved understanding of what signals released when by which cells requires novel tools for local detection of cell-secreted molecules. This paper reviews recent efforts by bioengineering and bioanalytical chemistry communities to develop biosensors for detecting molecules in extracellular space. Multiple topics including antibody-, enzyme- and aptamer-based biosensors for cell analysis as well as sensor miniaturization approaches are discussed.     

Synaptic adhesion molecules

Formation, differentiation and plasticity of synapses, the specialized cell-cell contacts through which neurons communicate, all require interactions between pre- and post-synaptic partners. Several synaptically localized adhesion molecules potentially capable of mediating these interactions have been identified recently. Functional studies suggest roles for some of them in target recognition (e.g. SYG-1 and sidekicks), formation and alignment of synaptic specializations (e.g. SynCAM, neuroligin and neurexin), and regulation of synaptic structure and function (e.g. cadherins and syndecan).     

Dual-affinity avidin molecules

A recently reported dual-chain avidin was modified further to contain two distinct, independent types of ligand-binding sites within a single polypeptide chain. Chicken avidin is normally a tetrameric glycoprotein that binds water-soluble d-biotin with extreme affinity (K(d) approximately 10(-15) M). Avidin is utilized in various applications and techniques in the life sciences and in the nanosciences. In a recent study, we described a novel avidin monomer-fusion chimera that joins two circularly permuted monomers into a single polypeptide chain. Two of these dual-chain avidins were observed to associate spontaneously to form a dimer equivalent to the wt tetramer. In the present study, we successfully used this scaffold to generate avidins in which the neighboring biotin-binding sites of dual-chain avidin exhibit two different affinities for biotin. In these novel avidins, one of the two binding sites in each polypeptide chain, the pseudodimer, is genetically modified to have lower binding affinity for biotin, whereas the remaining binding site still exhibits the high-affinity characteristic of the wt protein. The pseudotetramer (i.e., a dimer of dual-chain avidins) has two high and two lower affinity biotin-binding sites. The usefulness of these novel proteins was demonstrated by immobilizing dual-affinity avidin with its high-affinity sites. The sites with lower affinity were then used for affinity purification of a biotinylated enzyme. These "dual-affinity" avidin molecules open up wholly new possibilities in avidin-biotin technology, where they may have uses as novel bioseparation tools, carrier proteins, or nanoscale adapters.     

Determination of the concentration of ligand-specific molecules, found in mixtures with ligand-nonspecific molecules

A new method, which allows determination of the concentration of ligand-specific molecules in a mixture of these molecules with biochemically similar but ligand-unspecific molecules, is suggested. The method is based on a partial exhaustion of the mixture on a column with immobilized ligand and determination of the part of ligand-specific molecules presented in exhausted mixture. The concentration of monoclonal antibodies specific to bovine serum albumin in a commercial "Sigma" preparation and concentration of polyreactive immunoglobulins in a commercial "Sigma" preparation of bovine immunoglobulins were determined by suggested method.