Äidinmaito - terveysjuomaa ja normaalibakteereita

The chemical composition of breast milk has been studied in detail in the past decades. Hundreds of new antibacterial and antiviral components have been found. Several molecules have been found to promote the proper function of neonatal intestine. However, microbiological studies of breast milk have been, until recently, focused mainly on detecting harmful and pathogenic bacteria and viruses. Natural microbial diversity of human milk has not been widely studied before the work reported in this thesis. This is mainly because breast milk has traditionally been thought to be sterile - even if a certain amount of commensal bacteria have usually been detected in milk samples. The first part of this licentiate thesis contains a short literature review about the anatomy and physiology of breast feeding, human milk chemical and microbiological composition, mastitis, intestinal flora and bacteriocins. The second part reports on the experiments of the licentiate work, concentrating on the microbial diversity in the milk of healthy breast-feeding mothers, and the ability of these bacteria to produce antibacterial substances against pathogenic bacteria. The results indicate that human milk is a source of commensal bacteria for infant intestine. 509 random isolates from 40 breast milk samples were isolated and identified by 16S rRNA sequencing. Median bacterial count was about 600 colony forming units per milliliter. Over half of the isolates were staphylococci, and almost one third streptococci. The most common species were skin bacteria Staphylococcus epidermidis and oral bacteria Streptococcus salivarius and Streptococcus mitis. Lactic acid bacteria, identified as members of Lactobacillus-, Lactococcus- and Leuconostoc -genera, were found in five milk samples. Enterococci were found in three samples. A novel finding in this study is the capability of these commensal bacteria to inhibit the growth of pathogens. In 90 precent of the milk samples commensal bacteria inhibiting the growth of Staphylococcus aureus were found. In 40 precent of samples the colonies could block the growth completely. One fifth of the isolated Staph. epidermidis strains, half of Str. salivarius strains, and all lactic acid bacteria and enterococci could inhibit or block the growth of Staph. aureus. In further study also Listeria innocua- and Micrococcus luteus active isolates were found in 33 and 11 precent of milk samples (out of 140). Furthermore, two Lactococcus lactis isolates from the breast milk were shown to produce bacteriocin nisin, which is an antimicrobial molecule used as a food preservative. The importance of these human milk commensal bacteria in the development of newborn intestinal flora and immune system, as well as in preventing maternal breast infections, should be further explored.

N-Carbamoyl-DL-aspartic acid

CsHaN205, PL a = 6.438 (2), b = 7.486 (3), c = 8.048 (4)A, a = 72.2(1), fl = 80.8(1), y = 76.4 (1) °, D m = 1.65 (1) (flotation), D c = 1.64 Mg m -3, Z = 2. Final R = 0.095 for 1205 observed reflections. The molecule assumes the sterically least favourable conformation with the side chain carboxyl group staggered between the a-carboxyl group and the N atom attached to C '~. The ureido group takes part in two specific interactions involving two nearly parallel hydrogen bonds in one and two convergent hydrogen bonds in the other.

Stretching single DNA-molecules with temperature-stabilized optical tweezers

This thesis consists of two parts; in the first part we performed a single-molecule force extension measurement with 10kb long DNA-molecules from phage-λ to validate the calibration and single-molecule capability of our optical tweezers instrument. Fitting the worm-like chain interpolation formula to the data revealed that ca. 71% of the DNA tethers featured a contour length within ±15% of the expected value (3.38 µm). Only 25% of the found DNA had a persistence length between 30 and 60 nm. The correct value should be within 40 to 60 nm. In the second part we designed and built a precise temperature controller to remove thermal fluctuations that cause drifting of the optical trap. The controller uses feed-forward and PID (proportional-integral-derivative) feedback to achieve 1.58 mK precision and 0.3 K absolute accuracy. During a 5 min test run it reduced drifting of the trap from 1.4 nm/min in open-loop to 0.6 nm/min in closed-loop.

Inhibition of the biosynthesis of sterols by phenyl and phenolic compounds in rat liver

The presence of mitochondria increased the incorporation of [2-14C]mevalonate into sterols in a cell-free system from rat liver. Various phenyl and phenolic compounds inhibited the incorporation of mevalonate when added in vitro. p-Hydroxycinnamate, a metabolite of tyrosine, was the most powerful inhibitor among the compounds tested. Catechol, resorcinol and quinol were inhibitory at high concentrations. Organic acids lacking an aromatic ring were not inhibitory. Two hypocholesterolaemic drugs, Clofibrate (α-p-chlorophenoxyisobutyrate) and Clofenapate [α,4-(p-chlorophenyl)phenoxyisobutyrate], which are known to affect some step before the formation of mevalonate in the biosynthesis of cholesterol in vivo, showed inhibition at a step beyond the formation of mevalonate in vitro. The presence of the aromatic ring and the carboxyl group in a molecule appears to be necessary for the inhibition.

X-ray studies on crystalline complexes involving amino acids. IV. The structure of L-arginine L-ascorbate

L-Arginine ascorbate, C6HIsN40+.C6H706, a 1"1 crystalline complex between the amino acid arginineand the vitamin ascorbic acid, crystallizes in the monoclinic space group P21 with two formula units in a cell of dimensions a = 5.060 (8), b = 9.977 (9), c = 15.330 (13) A, fl = 97.5 (2) °. The structure was solved by the symbolic addition procedure and refined to an R of 0.067 for 1501 photographically observed reflec- tions. The conformation of the arginine molecule in the structure is different from any observed so far. The present structure provides the first description of the ascorbate anion unaffected by the geometrical constraints and disturbances imposed by the requirements of metal coordination. The lactone group and the deprotonated enediol group in the anion are planar and the side chain assumes a conformation which appears to be sterically the most favourable. In the crystals, the arginine molecules and the ascorbate anions aggregate separately into alternating layers. The molecules in the arginine layer are held together by interactions involving a-amino and ~t-carboxylate groups, a situation analogous to that found in proteins. The two layers of unlike molecules are interconnected primarily through the interactions of the side-chain guanidyl group of arginine with the ascorbate ion. These involve a specific ion-pair interaction accompanied by two convergent hydrogen bonds and another pair of nearly parallel hydrogen bonds.

Studies on crystalline complexes involving amino acids. V. The structure of L-serine-L-ascorbic acid

L-Serine-L-ascorbic acid, C3HTNOa. C6HsO6, a 1:1 complex between the amino acid serine and the vitamin ascorbic acid, crystallizes in the orthorhombic space group P2~2~2~ with four formula units in a cell of dimensions a = 5.335(3), b = 8.769(2), c = 25.782 (5) A. The structure was solved by direct methods and refined by full-matrix least squares to an R of 0.036 for 951 observed reflections. Both molecules are neutral in the structure. The conformation of the serine molecule is different from that observed in the crystal structures of L-serine, DL-serine and L-serine monohydrate. The enediol group in the ascorbic acid molecule is planar, whereas significant departures from planarity are observed in the lactone group. The conformation of this molecule is similar to that observed in arginine ascorbate. The unlike molecules aggregate into separate columns in the crystal structure. The columns are held together by hydrogen bonds. Among these, a pair of hydrogen bonds between the enediol group of ascorbic acid and the carboxylate group of serine provides a possible model for a specific interaction between ascorbic acid and a carboxylate ion.

Enzyme molecular choreography : studies on soluble inorganic pyrophosphatases

Inorganic pyrophosphatases (PPases, EC 3.6.1.1) hydrolyse pyrophosphate in a reaction that provides the thermodynamic 'push' for many reactions in the cell, including DNA and protein synthesis. Soluble PPases can be classified into two families that differ completely in both sequence and structure. While Family I PPases are found in all kingdoms, family II PPases occur only in certain prokaryotes. The enzyme from baker's yeast (Saccharomyces cerevisiae) is very well characterised both kinetically and structurally, but the exact mechanism has remained elusive. The enzyme uses divalent cations as cofactors; in vivo the metal is magnesium. Two metals are permanently bound to the enzyme, while two come with the substrate. The reaction cycle involves the activation of the nucleophilic oxygen and allows different pathways for product release. In this thesis I have solved the crystal structures of wild type yeast PPase and seven active site variants in the presence of the native cofactor magnesium. These structures explain the effects of the mutations and have allowed me to describe each intermediate along the catalytic pathway with a structure. Although establishing the ʻchoreographyʼ of the heavy atoms is an important step in understanding the mechanism, hydrogen atoms are crucial for the mechanism. The most unambiguous method to determine the positions of these hydrogen atoms is neutron crystallography. In order to determine the neutron structure of yeast PPase I perdeuterated the enzyme and grew large crystals of it. Since the crystals were not stable at ambient temperature, a cooling device was developed to allow neutron data collection. In order to investigate the structural changes during the reaction in real time by time-resolved crystallography a photolysable substrate precursor is needed. I synthesised a candidate molecule and characterised its photolysis kinetics, but unfortunately it is hydrolysed by both yeast and Thermotoga maritima PPases. The mechanism of Family II PPases is subtly different from Family I. The native metal cofactor is manganese instead of magnesium, but the metal activation is more complex because the metal ions that arrive with the substrate are magnesium different from those permanently bound to the enzyme. I determined the crystal structures of wild type Bacillus subtilis PPase with the inhibitor imidodiphosphate and an inactive H98Q variant with the substrate pyrophosphate. These structures revealed a new trimetal site that activates the nucleophile. I also determined that the metal ion sites were partially occupied by manganese and iron using anomalous X- ray scattering.

Synthesis, Reactivity and Biological Activity of 17β-HSD1 Inhibitors Based on a Thieno[2,3-d]pryrimidin-4(3H)-one Core

Breast cancer is the most common cancer in women in Western countries. In the early stages of development most breast cancers are hormone-dependent, and estrogens, especially estradiol, have a pivotal role in their development and progression. One approach to the treatment of hormone-dependent breast cancers is to block the formation of the active estrogens by inhibiting the action of the steroid metabolising enzymes. 17beta-Hydroxysteroid dehydrogenase type 1 (17beta-HSD1) is a key enzyme in the biosynthesis of estradiol, the most potent female sex hormone. The 17beta-HSD1 enzyme catalyses the final step and converts estrone into the biologically active estradiol. Blocking 17beta-HSD1 activity with a specific enzyme inhibitor could provide a means to reduce circulating and tumour estradiol levels and thus promote tumour regression. In recent years 17beta-HSD1 has been recognised as an important drug target. Some inhibitors of 17beta-HSD1 have been reported, however, there are no inhibitors on the market nor have clinical trials been announced. The majority of known 17beta-HSD1 inhibitors are based on steroidal structures, while relatively little has been reported on non-steroidal inhibitors. As compared with 17beta-HSD1 inhibitors based on steroidal structures, non-steroidal compounds could have advantages of synthetic accessibility, drug-likeness, selectivity and non-estrogenicity. This study describes the synthesis of large group of novel 17beta-HSD1 inhibitors based on a non-steroidal thieno[2,3-d]pyrimidin-4(3H)-one core. An efficient synthesis route was developed for the lead compound and subsequently employed in the synthesis of thieno[2,3-d]pyrimidin-4(3H)-one based molecule library. The biological activities and binding of these inhibitors to 17beta-HSD1 and, finally, the quantitative structure activity relationship (QSAR) model are also reported. In this study, several potent and selective 17beta-HSD1 inhibitors without estrogenic activity were identified. This establishment of a novel class of inhibitors is a progressive achievement in 17beta-HSD1 inhibitor development. Furthermore, the 3D-QSAR model, constructed on the basis of this study, offers a powerful tool for future 17beta-HSD1 inhibitor development. As part of the fundamental science underpinning this research, the chemical reactivity of fused (di)cycloalkeno thieno[2,3-d]pyrimidin-4(3H)-ones with electrophilic reagents, i.e. Vilsmeier reagent and dimethylformamide dimethylacetal, was investigated. These findings resulted in a revision of the reaction mechanism of Vilsmeier haloformylation and further contributed to understanding the chemical reactivity of this compound class. This study revealed that the reactivity is dependent upon a stereoelectronic effect arising from different ring conformations.

Novel Organo-Noble-Gas Hydrides

Noble gases are mostly known as inert monatomic gases due to their limited reactivity with other elements. However, the first predictions of noble-gas compounds were suggested by Kossel in 1916, by von Antropoff in 1924, and by Pauling in 1930. It took many decades until the first noble-gas compound, XePtF6, was synthesized by Neil Bartlett in 1962. This was followed by gradual development of the field and many noble-gas compounds have been prepared. In 1995, a family of noble-gas hydride molecules was discovered at the University of Helsinki. These molecules have the general formula of HNgY, where H is a hydrogen atom, Ng is a noble-gas atom (Ar, Kr, or Xe), and Y is an electronegative fragment. The first molecular species made include HXeI, HXeBr, HXeCl, HKrCl and HXeH. Nowadays the total number of prepared HNgY molecules is 23 including both inorganic and organic compounds. The first and only neutral ground-state argon compound, HArF, was synthetized in 2000. Helium and neon are the only elements in the periodic table that do not form neutral, ground-state molecules. In this Thesis, experimental preparation of eight novel xenon- and krypton-containing organo-noble-gas hydrides made from acetylene (HCCH), diacetylene (HCCCCH) and cyanoacetylene (HCCCN) are presented. These novel species include the first organic krypton compound, HKrCCH, as well as the first noble-gas hydride molecule containing two Xe atoms, HXeCCXeH. Other new compounds are HXeCCH, HXeCC, HXeC4H, HKrC4H, HXeC3N, and HKrC3N. These molecules are prepared in noble-gas matrices (krypton or xenon) using ultraviolet photolysis of the precursor molecule and thermal mobilization of the photogenerated H atoms. The molecules were identified using infrared spectroscopy and ab initio calculations. The formation mechanisms of the organo-noble-gas molecules are studied and discussed in this context. The focus is to evidence experimentally the neutral formation mechanisms of HNgY molecules upon global mobility of H atoms. The formation of HXeCCXeH from another noble-gas compound (HXeCC) is demonstrated and discussed. Interactions with the surrounding matrix and molecular complexes of the HXeCCH molecule are studied. HXeCCH was prepared in argon and krypton solids in addition to a Xe matrix. The weak HXeCCH∙∙∙CO2 complex is prepared and identified. Preparation of the HXeCCH∙∙∙CO2 complex demonstrates an advanced approach to studies of HNgY complexes where the precursor complex (HCCH∙∙∙CO2) is obtained using photolysis of a larger molecule (propiolic acid).

Parity violation in molecular magnetic resonance properties

The Standard Model of particle physics consists of the quantum electrodynamics (QED) and the weak and strong nuclear interactions. The QED is the basis for molecular properties, and thus it defines much of the world we see. The weak nuclear interaction is responsible for decays of nuclei, among other things, and in principle, it should also effects at the molecular scale. The strong nuclear interaction is hidden in interactions inside nuclei. From the high-energy and atomic experiments it is known that the weak interaction does not conserve parity. Consequently, the weak interaction and specifically the exchange of the Z^0 boson between a nucleon and an electron induces small energy shifts of different sign for mirror image molecules. This in turn will make the other enantiomer of a molecule energetically favorable than the other and also shifts the spectral lines of the mirror image pair of molecules into different directions creating a split. Parity violation (PV) in molecules, however, has not been observed. The topic of this thesis is how the weak interaction affects certain molecular magnetic properties, namely certain parameters of nuclear magnetic resonance (NMR) and electron spin resonance (ESR) spectroscopies. The thesis consists of numerical estimates of NMR and ESR spectral parameters and investigations of the effects of different aspects of quantum chemical computations to them. PV contributions to the NMR shielding and spin-spin coupling constants are investigated from the computational point of view. All the aspects of quantum chemical electronic structure computations are found to be very important, which makes accurate computations challenging. Effects of molecular geometry are also investigated using a model system of polysilyene chains. PV contribution to the NMR shielding constant is found to saturate after the chain reaches a certain length, but the effects of local geometry can be large. Rigorous vibrational averaging is also performed for a relatively small and rigid molecule. Vibrational corrections to the PV contribution are found to be only a couple of per cents. PV contributions to the ESR g-tensor are also evaluated using a series of molecules. Unfortunately, all the estimates are below the experimental limits, but PV in some of the heavier molecules comes close to the present day experimental resolution.

Studies of new inorganic species using relativistic quantum chemistry

In the present work the methods of relativistic quantum chemistry have been applied to a number of small systems containing heavy elements, for which relativistic effects are important. First, a thorough introduction of the methods used is presented. This includes some of the general methods of computational chemistry and a special section dealing with how to include the effects of relativity in quantum chemical calculations. Second, after this introduction the results obtained are presented. Investigations on high-valent mercury compounds are presented and new ways to synthesise such compounds are proposed. The methods described were applied to certain systems containing short Pt-Tl contacts. It was possible to explain the interesting bonding situation in these compounds. One of the most common actinide compounds, uranium hexafluoride was investigated and a new picture of the bonding was presented. Furthermore the rareness of uranium-cyanide compounds was discussed. In a foray into the chemistry of gold, well known for its strong relativistic effects, investigations on different gold systems were performed. Analogies between Au$^+$ and platinum on one hand and oxygen on the other were found. New systems with multiple bonds to gold were proposed to experimentalists. One of the proposed systems was spectroscopically observed shortly afterwards. A very interesting molecule, which was theoretically predicted a few years ago is WAu$_{12}$. Some of its properties were calculated and the bonding situation was discussed. In a further study on gold compounds it was possible to explain the substitution pattern in bis[phosphane-gold(I)] thiocyanate complexes. This is of some help to experimentalists as the systems could not be crystallised and the structure was therefore unknown. Finally, computations on one of the heaviest elements in the periodic table were performed. Calculation on compounds containing element 110, darmstadtium, showed that it behaves similarly as its lighter homologue platinum. The extreme importance of relativistic effects for these systems was also shown.

Science-based Industries Coin

Obverse: 10 Lirot silver coin, in the center stylized design of the atomic reactor building at Nahal Sorek. Reverse: Design of a cog-wheel rotating molecule.

Science-based Industries Coin

Obverse: silver 10 Lirot coin, in the center atomic reactor at Nahal Sorek. Reverse: design of a cog-wheel rotating molecule.

Intermolecular Interactions of Noble-Gas-Containing Species

The importance of intermolecular interactions to chemistry, physics, and biology is difficult to overestimate. Without intermolecular forces, condensed phase matter could not form. The simplest way to categorize different types of intermolecular interactions is to describe them using van der Waals and hydrogen bonded (H-bonded) interactions. In the H-bond, the intermolecular interaction appears between a positively charged hydrogen atom and electronegative fragments and it originates from strong electrostatic interactions. H-bonding is important when considering the properties of condensed phase water and in many biological systems including the structure of DNA and proteins. Vibrational spectroscopy is a useful tool for studying complexes and the solvation of molecules. Vibrational frequency shift has been used to characterize complex formation. In an H-bonded system A∙∙∙H-X (A and X are acceptor and donor species, respectively), the vibrational frequency of the H-X stretching vibration usually decreases from its value in free H-X (red-shift). This frequency shift has been used as evidence for H-bond formation and the magnitude of the shift has been used as an indicator of the H-bonding strength. In contrast to this normal behavior are the blue-shifting H-bonds, in which the H-X vibrational frequency increases upon complex formation. In the last decade, there has been active discussion regarding these blue-shifting H-bonds. Noble-gases have been considered inert due to their limited reactivity with other elements. In the early 1930 s, Pauling predicted the stable noble-gas compounds XeF6 and KrF6. It was not until three decades later Neil Bartlett synthesized the first noble-gas compound, XePtF6, in 1962. A renaissance of noble-gas chemistry began in 1995 with the discovery of noble-gas hydride molecules at the University of Helsinki. The first hydrides were HXeCl, HXeBr, HXeI, HKrCl, and HXeH. These molecules have the general formula of HNgY, where H is a hydrogen atom, Ng is a noble-gas atom (Ar, Kr, or Xe), and Y is an electronegative fragment. At present, this class of molecules comprises 23 members including both inorganic and organic compounds. The first and only argon-containing neutral chemical compound HArF was synthesized in 2000 and its properties have since been investigated in a number of studies. A helium-containing chemical compound, HHeF, was predicted computationally, but its lifetime has been predicted to be severely limited by hydrogen tunneling. Helium and neon are the only elements in the periodic table that do not form neutral, ground state molecules. A noble-gas matrix is a useful medium in which to study unstable and reactive species including ions. A solvated proton forms a centrosymmetric NgHNg+ (Ng = Ar, Kr, and Xe) structure in a noble-gas matrix and this is probably the simplest example of a solvated proton. Interestingly, the hypothetical NeHNe+ cation is isoelectronic with the water-solvated proton H5O2+ (Zundel-ion). In addition to the NgHNg+ cations, the isoelectronic YHY- (Y = halogen atom or pseudohalogen fragment) anions have been studied with the matrix-isolation technique. These species have been known to exist in alkali metal salts (YHY)-M+ (M = alkali metal e.g. K or Na) for more than 80 years. Hydrated HF forms the FHF- structure in aqueous solutions, and these ions participate in several important chemical processes. In this thesis, studies of the intermolecular interactions of HNgY molecules and centrosymmetric ions with various species are presented. The HNgY complexes show unusual spectral features, e.g. large blue-shifts of the H-Ng stretching vibration upon complexation. It is suggested that the blue-shift is a normal effect for these molecules, and that originates from the enhanced (HNg)+Y- ion-pair character upon complexation. It is also found that the HNgY molecules are energetically stabilized in the complexed form, and this effect is computationally demonstrated for the HHeF molecule. The NgHNg+ and YHY- ions also show blue-shifts in their asymmetric stretching vibration upon complexation with nitrogen. Additionally, the matrix site structure and hindered rotation (libration) of the HNgY molecules were studied. The librational motion is a much-discussed solid state phenomenon, and the HNgY molecules embedded in noble-gas matrices are good model systems to study this effect. The formation mechanisms of the HNgY molecules and the decay mechanism of NgHNg+ cations are discussed. A new electron tunneling model for the decay of NgHNg+ absorptions in noble-gas matrices is proposed. Studies of the NgHNg+∙∙∙N2 complexes support this electron tunneling mechanism.

Deriving structural information from non-coding ribonucleic acids by mass spectrometry

The purpose of this study is to describe the development of application of mass spectrometry for the structural analyses of non-coding ribonucleic acids during past decade. Mass spectrometric methods are compared of traditional gel electrophoretic methods, the characteristics of performance of mass spectrometric, analyses are studied and the future trends of mass spectrometry of ribonucleic acids are discussed. Non-coding ribonucleic acids are short polymeric biomolecules which are not translated to proteins, but which may affect the gene expression in all organisms. Regulatory ribonucleic acids act through transient interactions with key molecules in signal transduction pathways. Interactions are mediated through specific secondary and tertiary structures. Posttranscriptional modifications in the structures of molecules may introduce new properties to the organism, such as adaptation to environmental changes or development of resistance to antibiotics. In the scope of this study, the structural studies include i) determination of the sequence of nucleobases in the polymer chain, ii) characterisation and localisation of posttranscriptional modifications in nucleobases and in the backbone structure, iii) identification of ribonucleic acid-binding molecules and iv) probing of higher order structures in the ribonucleic acid molecule. Bacteria, archaea, viruses and HeLa cancer cells have been used as target organisms. Synthesised ribonucleic acids consisting of structural regions of interest have been frequently used. Electrospray ionisation (ESI) and matrix-assisted laser desorption ionisation (MALDI) have been used for ionisation of ribonucleic analytes. Ammonium acetate and 2-propanol are common solvents for ESI. Trihydroxyacetophenone is the optimal MALDI matrix for ionisation of ribonucleic acids and peptides. Ammonium salts are used in ESI buffers and MALDI matrices as additives to remove cation adducts. Reverse phase high performance liquid chromatography has been used for desalting and fractionation of analytes either off-line of on-line, coupled with ESI source. Triethylamine and triethylammonium bicarbonate are used as ion pair reagents almost exclusively. Fourier transform ion cyclotron resonance analyser using ESI coupled with liquid chromatography is the platform of choice for all forms of structural analyses. Time-of-flight (TOF) analyser using MALDI may offer sensitive, easy-to-use and economical solution for simple sequencing of longer oligonucleotides and analyses of analyte mixtures without prior fractionation. Special analysis software is used for computer-aided interpretation of mass spectra. With mass spectrometry, sequences of 20-30 nucleotides of length may be determined unambiguously. Sequencing may be applied to quality control of short synthetic oligomers for analytical purposes. Sequencing in conjunction with other structural studies enables accurate localisation and characterisation of posttranscriptional modifications and identification of nucleobases and amino acids at the sites of interaction. High throughput screening methods for RNA-binding ligands have been developed. Probing of the higher order structures has provided supportive data for computer-generated three dimensional models of viral pseudoknots. In conclusion. mass spectrometric methods are well suited for structural analyses of small species of ribonucleic acids, such as short non-coding ribonucleic acids in the molecular size region of 20-30 nucleotides. Structural information not attainable with other methods of analyses, such as nuclear magnetic resonance and X-ray crystallography, may be obtained with the use of mass spectrometry. Sequencing may be applied to quality control of short synthetic oligomers for analytical purposes. Ligand screening may be used in the search of possible new therapeutic agents. Demanding assay design and challenging interpretation of data requires multidisclipinary knowledge. The implement of mass spectrometry to structural studies of ribonucleic acids is probably most efficiently conducted in specialist groups consisting of researchers from various fields of science.