Interaction of amino acids and related compounds with neutral polyadenylic acid: a proton magnetic resonance study

Simple item page
dc.contributor.authorRaszka, Matthew Joseph
dc.date.accessioned2009-09-09T20:24:57Z
dc.date.available2009-09-09T20:24:57Z
dc.date.issued1971
dc.descriptionTypescript.
dc.descriptionThesis (Ph. D.)--University of Hawaii, 1971.
dc.descriptionBibliography: leaves 157-164.
dc.descriptionxii, 164 l illus
dc.description.abstractBy examining not only proton magnetic resonance (PMR) line separation but also actual chemical shifts of individual aromatic PMR lines of neutral-pH polyriboadenylic acid (poly A), it was established that poly A line separation reflects the degree of base stacking in the single-stranded polynucleotide under a variety of conditions. By monitoring the behavior of poly A in the presence of 19 amino acids and 10 derivatives, it was concluded that a number of aromatic and aliphatic compounds can interact with the polynucleotide via intercalation between adjacent bases, which thereby become destacked. The strength of binding depends primarily on the size, or hydrophobic character, as with the following amino acids: L-Trp>L-Phe>L-His L-Leu >L-Ile>L-Met >L-Vah~L-Pro >L-Ala>Gly but the binding can be aided (as with tryptamine, phenethylamine and histamine) or hindered (as with 3-indolepropionic, 3-phenylpropionic and dihydrourocanic acids) by an electrostatic interaction with the polynucleotide phosphates. It was shown that the PMR melting temperature (T) of 0.04M m - + poly A in 0.2M phosphate buffer, pH =7, was lowered 6±1°C upon addition of 0.15M L-Phe. Other amino acids caused a Tm depression m to an extent reflecting their binding strength. The binding of a number v of compounds was quantitated in terms of association constant K for a 1: 1 interactant: polynucleotide base complex, with the help of a computerized least-squares fit of PMR chemical shifts. Values ranged from K=5-10 M^-1 for L-Trp to K<l for the aliphatic amino acids. Indole heteroaromatics yielded values as high as 250 M- 1 (N, N-dimethyltryptamine) and 100 M-1 (tryptamine). The effect of higher temperature of poly A line separation is similar to that observed upon addition of interactants which are capable of intercalation; however, direct evidence for intercalation was provided only by the indole heteroaromatics, which induced diamagnetic (upfield) shifts in the poly A H-2 line, and probably also in the H-8line. Apposition of molecular surfaces is generally a prerequisite for the induction of diamagnetic shifts, which additionally precludes nonspecific medium effects as a possible cause of the observed shifts. In addition to polynucleotide destacking caused by weak intercalation, another mode of binding was deduced for several polar amino acids. In this case, the opposite effect, stabilization of the single helix, was indicated, presumably by ionic chelation to the polynucleotide phosphates (in the case of L-Lys and L-Orn) or conceivably by stabilizing individual monomer units against thermal agitation (in the case of Gly and L-Ser). Preliminary results were obtained for the interaction of several amino acids with neutral polyribouridylic acid (poly U) and polyriboinosinic acid (poly I). In both cases the following order of interaction tendencies was inferred: L-Trp>L-Phe> L-His. Negative results were obtained with neutral polycytidylic acid (poly C). The study represents a beginning attempt at understanding the molecular bases which underlie protein--polynucleotide interaction and specificity.
dc.identifier.urihttp://hdl.handle.net/10125/12164
dc.language.isoen-US
dc.publisher[Honolulu]
dc.relationTheses for the degree of Doctor of Philosophy (University of Hawaii (Honolulu)). Biomedical Sciences (Biophysics); no. 382
dc.rightsAll UHM dissertations and theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission from the copyright owner.
dc.subjectAmino acids
dc.subjectPolyadenylic acid
dc.titleInteraction of amino acids and related compounds with neutral polyadenylic acid: a proton magnetic resonance study
dc.typeThesis
dc.type.dcmiText

Files

Original bundle
Now showing 1 - 2 of 2
No Thumbnail Available
Name:
uhm_phd_7210157_uh.pdf
Size:
3.15 MB
Format:
Adobe Portable Document Format
Description:
Version for UH users
Download
No Thumbnail Available
Name:
uhm_phd_7210157_r.pdf
Size:
3.2 MB
Format:
Adobe Portable Document Format
Description:
Version for non-UH users. Copying/Printing is not permitted
Download

Collections

Ph.D. - Biomedical Sciences (Biophysics)