Biomedical subjects
Publications and source records attributed to D W Armstrong.
The potential for obtaining enhanced purities and for achieving greater homogeneity of materials in microgravity first attracted biotechnologists to space bioprocessing. This is but one of the benefits of microgravity. This review discusses the unique opportunities of space biotechnology and the diverse means to achieve microgravity conditions.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
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Different drug stereoisomers can have different physiological and therapeutic effects. Difficulties in separating optical isomers often make it impractical to market stereochemically pure products or to monitor isomeric contamination. This is not thought to be a problem with drugs isolated from biological sources (the alkaloids, for example). However, small amounts of isomeric impurities also exist in many biological systems. More importantly the isolation and purification process can cause partial or complete racimization in some cases. Great care must be taken in the handling of some drugs and an efficient, sensitive means to monitor racimization is important. Liquid chromatographic separation on a chiral beta-cyclodextrin bonded phase can be an effective technique in many cases. Its use in separating optical isomers of dl-scopolamine, dl-hyoscyamine, dl-homatropine, and dl-cocaine is discussed.
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For many drugs, only racemic mixtures are available for clinical use. Because different stereoisomers of drugs often cause different physiological responses, the use of pure isomers could elicit more exact therapeutic effects. Differential complexation of a variety of drug stereoisomers by immobilized beta-cyclodextrin was investigated. Chiral recognition and racemic resolution were observed with a number of compounds from such clinically useful classes as beta-blockers, calcium-channel blockers, sedative hypnotics, antihistamines, anticonvulsants, diuretics, and synthetic opiates. Separation of the diastereomers of the cardioactive and antimalarial cinchona alkaloids and of two antiestrogens was demonstrated as well. Three dimensional projections of beta-cyclodextrin complexes of propanolol, which is resolved by this technique, and warfarin, which is not, are compared. These studies have improved the understanding and application of the chiral interactions of beta-cyclodextrin, and they have demonstrated a means to measure optical purity and to isolate or produce pure enantiomers of drugs. In addition, this highly specific technique could also be used in the pharmacological evaluation of enantiomeric drugs.
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Effects of solvent composition and ligand variation on the retention of organometallic compounds have been studied using an amino, an octadecylsilica (ODS) and a beta-cyclodextrin (beta-CD) bonded phase column in either a normal-phase or a reversed-phase mode. The retention behavior for the organometallic compounds with the amino column can be rationalized using the displacement model. The "apparent" molecular areas are greater for compounds capable of strong hydrogen bonding. The retention in the ODS column roughly follows an argument based on the expected solubility behavior while mixed retention mechanisms are involved for the solubility behavior while mixed retention mechanisms are involved for the beta-CD column, i.e. both inclusion process and solubility or solvophobic interactions are possibly operative.
The theory and mechanism for the reversed-phase liquid chromatographic separation of macromolecules was somewhat vague and controversial until recently when the Flory-Huggins theory of dilute polymer solutions was used to provide the technique with a firm theoretical foundation. As a result of this treatment, the concept of a critical mobile phase composition (Xc) has been introduced to liquid chromatography. Macromolecular solutes below Xc are completely retained, while above Xc they are rapidly eluted. Because the capacity factor of a solute is related to Xc, traditional chromatographic parameters such as theoretical plate number have little meaning. A brief summary of the history of chromatographic polymer separations that foreshadows the current theory is given. A review and an evaluation of the current mechanistic status of macromolecular chromatography are presented. Also considered is the use of adsorption theory, "small molecule" theory, and solvophobic chromatographic theory for macromolecular separations. The theory and separation mechanism are relatively straightforward for synthetic polymers but tend to be more complex and less clearcut for biological polymers.
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Alayl, [ 14c]-alanyl, phenylalanyl, and methionyl adenylates have been synthesized in high yields and relatively good purities. Elemental analysis 1H nmr and ir spectra have been utilized for the characterization of these extremely labile compounds. The present synthesis, which uses readily available N-tert-butoxycarbonyl amino acids, is compared with previous methods.
Using quantitative gel filtration techniques partition coefficients, Kp-values, have been determined between aqueous cationic micellar hexadecyltrimethylammonium bromide, CTAB, and several biomonomer. Kp-values for 5'-adenylic acid, 5'-cytidylic acid, 5'-guanylic acid, 5'-uridylic acid and 5'-thymidylic acid are 1,400 +/- 150. Nucleotides bind to CTAB micelles effectively, but nonselectively. Conversely, the binding of tRNAs to micellar CTAB is selective. Kp-values for glutamic acid II, tyrosine and phenylalanine tRNAs (in 1.0MNaCl) are 520, 3,100 and 5,600, respectively. Kp-values for the binding of alanine, arginine, aspartic acid, glutamic acid, glycine, histidine, phenylalanine, serine, threonine and tryptophan to micellar CTAB are less than 8. Conversion of unitless Kp-values for the binding of amino acids, nucleotides and nucleosides to both anionic and cationic micelles, to K (in 1/g) values allows the comparison of clays and micelles as prebiotic concentrating media. Using correlations between surface densities of the biomonomers and their binding constants, it is shown that aqueous micelles (at pH = 8) are a better concentrating media than are clays.
Partition coefficients (Kp) of phenylalanine, glutamic acid-II and tyrosine tRNAs between water and micellar cetyltrimethylammonium chloride (CTACl) have been determined to be 5600, 520 and 3100, respectively, by gel filtration on Sephadex G-100-120. Equations for obtaining Kp values from quantitative gel filtration have also been derived. The use of this method for the separation of tRNAs is demonstrated.
Oligomerization of 5' -TMP in water pools entrapped by dodecyl-ammonium chloride surfactant aggregates in benzene: hexane in the presence of dicyanodiimide at temperatures ranging from 21 degree -72 degree resulted in the formation of linear and cyclic oligonucleotides containing up to pentamers. Effects of temperature, time and surfactants have been examined. Rate constants for the formation of oligomers have been determined at five different temperatures. These data afforded values of (formula: see text). Prebiotic significance of these results are discussed.