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F B Howard

Publications and source records attributed to F B Howard.

36 records · Page 2Linked to original sources
PubMed1977

Structure of poly 8-bromoadenylic acid; conformational studies by CPF energy calculations.

Poly 8-bromoadenylic acid [poly(BBrA)] is the only known all-syn polynucleotide. It shows a helix-coil transition with a melting curve centred around 55 degrees C. Energy calculations based on classical potential functions have been used to explore the three-dimensional structure of this polymer in helix and random coil. It is concluded that the ordered state is a helix of two parallel strands with a two-fold rotation axis, and the duplex is stabilised by hydrogen bonds involving N1 and H6. Each strand has a conformation with C3' endo geometry, phi' = 216 degrees, omega' = 280 degrees, omega = 294 degrees, phi = 179 degrees, chi = 243 degrees and psi = 57 degrees. Such a conformation leads to approximately 8 nucleotide units per turn of the helix and an axial rise of 3.9A degrees. The structure of poly(8BrA) has been compared with that of the related polymer poly(A) which forms a double helical structure in acidic conditions with bases in the anti conformation and with interstrand hydrogen-bonds between N7 and H6. This is the first time that a specific geometrical model of a novel polynucleotide structure has been produced initially by potential energy calculations, though such calculations on a number of known structures have been reported previously.

Models, Molecular↗
PubMed1976

Poly(2-aminoadenylic acid): interaction with poly(uridylic acid).

Poly(2-aminoadenylic acid) forms both double and triple helices with poly(uridylic acid) [poly(U)]. The 2-amino group forms a third hydrogen bond, elevating the 2 leads to 1 transition temperature by 33 degrees C. The third strand, however, has about the same stability as poly(A)-2poly(U), as measured by Tm 3 leads to 2. This selective stabilization of the two-stranded helix results in a much greater resolution of the differnt thermal transitions than that observed in analogous polynucleotide systems. In contrast to other A, U systems 3 leads to 1 and 2 leads to 3 transitions are not observed under any conditions, and the triple helix always undergoes a 3 leads to 2 transition even at very high ionic strength. A 1:1 mixture of poly(2NH2A) and poly(U) exhibits no transient formation of 1:2 complex, unlike similar mixtures of poly(A) with poly(U) and poly(T). This difference is evidently due to a more rapid displacement reaction: [poly(2NH2A) + poly(2NH2A)-2poly(U) leads to 2 poly(2NH2A)-poly(U)] With poly(2NH2A) than with poly(A). We describe a method for establishing the combining ratios of polynucleotide complexes which used a computer to calculate the angles of intersection of mixing curves as explicit and continuous functions of the wavelength. The wavelength dispersions of the angles of intersection determine optimum wavelengths for establishing stoichiometry and can also provide reliable negative evidence that presumably plausible complexes are not formed. Analogous computer procedures have been developed to determine wavelengths which are selective for the formation of both 1:1 and 1:2 complexes. Infrared spectra of the 1:1 and 1:2 complexes resemble those of other A, U homoribopolynucleotide helices in having two and three strong bands, respectively, in the region of carbonyl stretching vibrations. CD spectra of the two complexes are unusual in having negative first extrema of moderate intensity. We attribute these extrema to intrastrand interactions of strong, well-resolved transitions at 278 nm (B2u) of the 2-aminoadenine residues. The CD spectra are correlated with those of other polynucleotide helices.

Autoanalysis↗
PubMed1975

Poly(8-bromoadenylic acid): synthesis and characterization of an all-syn polynucleotide.

Poly(8-bromoadenylic acid) (poly(8-BrA)) has been synthesized by polymerization of 8-BrADP with polynucleotide phosphorylase in the presence of oligonucleotide primers. In the absence of oligonucleotides, significant (i.e. more than 1%) polymerization does not occur. Oligo(I) primer was removed selectively from the polymer with ribonuclease T1 to yield the homopolymer, poly(8-BrA). End group analysis, based on quantitative infrared measurement of the (Ip)3I-primed polymer, indicates an average degree of polymerization of about 70 residues. The primed polymers and the homopolymer appear to have similar helical structures, probably double-stranded with mutual hydrogen bonding interaction of BrA residues. Preliminary NMR observations of poly(8-BrA) with a tetrainosinic acid primer at the 5' ends of the polymer chain ((Ip)3I-(8-BrA)n) are consistent with the existence of a rigid helical structure below the melting range of the primed polymer. Above the melting range (81 degrees) the H1' coupling constants of (Ip)3I-(8-BrA)n and of polyadenylic acid (poly(A)) suggest a significantly higher population of C3' endo conformation of ribose residues in the primed polymer than in poly(A) at 81 degrees.

Adenosine Monophosphate↗
PubMed1969

Interbase vibrational coupling in G:C polynucleotide helices.

The carbonyl stretching vibrations of G and C residues undergo frequency changes when a helical complex is formed from nonordered G and C components. We have prepared a series of two-stranded G:C helices having chemical and isotopic ((18)O) substitutions which lead to variation of the observed vibrational frequencies. Infrared spectra of these helices clearly demonstrate that vibrational coupling occurs between the guanine and cytosine residues in the helix. As a result of this coupling through the hydrogen bonds, the two carbonyl bands undergo frequency shifts of equal magnitude and opposite sign, with mixing of G and C character in the observed interacted vibrations.

Cytosine Nucleotides↗