Circular dichroism of nucleoside derivatives. IV. Uracil derivatives

Miles, Daniel W.; Robins, Morris J.; Robins, Roland K.; Winkley, Michael W.; Eyring, Henry

doi:10.1021/ja01032a005

Cited by 75 publications

(25 citation statements)

References 6 publications

(8 reference statements)

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“…These studies have yielded some useful rules and diagrams (1)(2)(3)(4)(5)(6)(7)(8)(9)(10) relating the sign of the first CD band to anomeric configuration and to sugar-base torsion angle. Several excellent reviews in this area are now available (11)(12)(13)(14)(15).…”

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confidence: 99%

Calculations of the circular dichroism of adenosine derivatives constrained in the syn form

Miles¹,

Farmer²,

Eyring³

1980

Proc. Natl. Acad. Sci. U.S.A.

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The rotational strengths of the four longer wavelength transitions, BsU, Bju, and the two El , of adenosine derivatives constrained in the syn form have been investigated theoretically and experimentally. The theory combines a complete neglect of differential overlap version S (CNDO/S) description of the base with a generalized bond exciton metho by means of a matrix method. Rotational strength wheels for these transitions showing the rotational strength as a function of the glycosidic rotational angles are presented and sector rules discussed. Similar sector rules are predicted for purine nucleoside derivatives containing the 6-amino substituent, regardless of heteroatom content at positions 1 or 3 of the base. The sector rules for the Bs" rotational strength of purine nucleosides lacking the 6-amino substituent are strongly influenced by aza substitution. The circular dichroism spectra of 3-deazaadenosine, 8-a-hydroxyisopropyl)adenosine, and other purine nucleosides having a strong preference for the syn conformation are presented and compared with the theoretical results.Circular dichroism (CD) has been used extensively to study the conformation of nucleosides and nucleotides in solution. These studies have yielded some useful rules and diagrams (1-10) relating the sign of the first CD band to anomeric configuration and to sugar-base torsion angle. Several excellent reviews in this area are now available (11)(12)(13)(14)(15) We report here a theoretical CD study of some purine nucleosides closely related to adenosine which are conformationally restricted more or less to the syn conformation. The complete neglect of differential overlap version S (CNDO/S) procedure of Del Bene and Jaffe (27, 28) is used to calculate the optical parameters of the purine bases instead of our PariserParr-Pople method used in previous calculations (17,18). This and other modifications of the theoretical procedure have improved agreement between experimental data and theoretical results.COMPUTATIONAL METHODS The self-consistent field method has been widely used for the study of the electronic structure of molecules. The molecular orbitals 0t are expressed as linear combination of atomic orbitals 4u according to the equationThe coefficients Ct of the molecular orbital matrix are the solutions of the Hartree-Fock-Roothaan equations 3398The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact.

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confidence: 99%

Calculations of the circular dichroism of adenosine derivatives constrained in the syn form

Miles¹,

Farmer²,

Eyring³

1980

Proc. Natl. Acad. Sci. U.S.A.

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“…It is well known that for ATP analogues with bulky groups at the eighth position of the adenine ring, steric hindrance causes the syn-anti equilibrium with respect to the N-glycoside bond to be very much shifted towards the syn conformation [22,23,38,39]. In the present study, we utilized 8-N 3 -ATP and 8-Br-ATP, which favor the formation of the syn conformation with respect to the N-glycoside bond of ATP, to probe the structures of the active sites of skeletal and smooth-muscle myosins.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the interaction of myosin with ATP analogues having the syn conformation with respect to the adenine‐ribose bond

Maruta

Ohki

Kambara

et al. 1998

European Journal of Biochemistry

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Numerous analytical experiments have shown that, in solution, ATP analogues with bulky substitutions at the eighth position of the adenine ring predominantly assume the syn conformation with respect to the adenineϪribose bond. Two such analogues, 3′-O-(N-methylanthraniloyl)-8-azido-ATP (Mant-8-N 3-ATP) and 8-Br-ATP, were synthesized and used to probe the conformation of the ATP-binding site of myosin. In the presence of these analogues, actomyosin was rapidly dissociated; Mg 2ϩ -dependent ATP hydrolysis was significantly activated by actin; and P i bursting was observed. For skeletal myosin, however, these analogues failed to support actin translocation, and they did not significantly enhance the intrinsic tryptophan fluorescence of skeletal muscle myosin subfragment-1 (SKE S-1). These results suggest that although myosin**/ADP/P i intermediates can be formed with these analogues, the crucial conformational changes required for cross-bridge cycling do not occur in skeletal muscle myosin. The conformations of the ATP-binding sites of skeletal and smooth-muscle myosin were compared using the ternary complexes, myosin-ADP-beryllium fluoride (BeFn) or myosin-ADP-aluminium fluoride (AlF Ϫ 4 ). In Al F Ϫ 4 complexes, Mant-8-N 3 -ADP affinity labeled the N-terminal 29-kDa domain of smooth-muscle myosin subfragment-1 (SM S-1), as did ATP analogues having the anti conformation, whereas it labeled the Cterminal 20-kDa domain of skeletal S-1. In smooth muscle BeFn complexes, Mant-8-N 3 -ADP was equally likely to cross-link to the 29-kDa N-terminal and the 25-kDa C-terminal domains. These analogues induced smooth muscle actomyosin super-precipitation and increased intrinsic tryptophan fluorescence to the same degree as ATP itself. As was expected from above results, the analogues supported smoothmuscle-myosin-induced actin translocation. These results suggest that smooth-muscle myosin adopts the eight-substituted ATP analogue in the normal conformation, but skeletal muscle myosin does not. This reflects the likely differences in the structures of their respective ATPase sites.Keywords : myosin; ATP analogue; photoaffinity labeling; muscle contraction; ATPase site.Myosin is a mechanochemical enzyme involved in diverse contractile events in cells. While the primary structure of the head domain is highly conserved among various myosin isoforms, their characteristics as motor molecules and the mechanisms of their regulation differ [1Ϫ3]. Even among conventional vertebrate isoforms, skeletal and smooth-muscle myosins are quite distinct from each other: the former is characterized by a high-rate, actin-activated ATP hydrolysis, fast actin-translocating velocity and comparatively low force generation [4], whereas the latter is characterized by a slow rate of ATP hydrolysis, slow actin-translocating velocity and relatively high force generation. In addition, smooth-muscle myosin motor activity is regulated by light chain phosphorylation, but skeletal myosin motor activity is unregulated by phosphorylation [1,5,6]. The molecular mec...

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“…Calculations of the rotational strengths ofpyrimidine nucleosides have previously been based on models in which the molecule is partitioned into spatially separated groups (30)(31)(32)(33)(34)(35)(36)(37)(38)(39) (71) with spectroscopic parameterization (CNDO/S) is used without modification except for changes designed to enhance the efficiency of the computation. The Nishimoto-Magata approximation was used to represent the two-center Coulomb repulsion integrals, and excited states were generated from configuration interaction between the 120 lowest energy one-electron excitations.…”

Section: Theorymentioning

confidence: 99%

“…Along with difficulties associated with treating the weak perturbation effects of the nonchromophoric sugar, this incomplete knowledge has hindered the development of theoretical models for calculating the rotatory parameters and extracting stereochemical information from them. In spite of these problems, CD studies of nucleosides have produced some useful rules and diagrams relating the sign of the first CD band to anomeric configuration and to conformation (10,(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(52)(53)(54)(55)(56)(57)(58)(59)(60)(61).…”

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confidence: 99%

Optical activity and electronic absorption spectra of some simple nucleosides related to cytidine and uridine: all-valence-shell molecular orbital calculations.

Miles¹,

Redington²,

Miles³

et al. 1981

Proc. Natl. Acad. Sci. U.S.A.

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The circular dichroism and electronic absorption of three simple model systems for cytidine and uridine have been measured to 190 nm. The molecular spectral properties (excitation wavelengths, oscillator strengths, rotational strengths, and polarization directions) and electronic transitional patterns were investigated by using wave functions of the entire nucleoside with the goal of establishing the reliability of the theoretical method. The computed electronic absorption quantities were shown to be in satisfactory agreement with experimental data. It was found that the computed optical rotatory strengths of the B2. and El.electronic transitions and lowest observed n-ir* transition are in good agreement with experimental values. Electronic transitions were characterized by their electronic transitional patterns derived from population analysis of the transition density matrix.The theoretical rotational strengths associated with the B2. and El. transitions stabilize after the use of just a few singly excited configurations in the configuration interaction basis and, hypothetically, are more reliable as indicators of conformation in pyrimidine nucleosides related to cytidine.Spectroscopic studies of the nucleic acid bases and their derivatives have appeared continuously over the past quarter century (1-40). Many of these studies were motivated by the prospect of obtaining stereochemical information from changes in the absorption and optical rotation spectra of the nucleic acids and their models (41-51). More recently, the increasing importance of slightly modified versions of the nucleic acid monomers as potential therapeutic agents has accentuated the importance of optical studies in this area, particularly circular dichroism (CD) studies, which indirectly give one stereochemical information (10-18, 31-41, 52-61). The biological significance of the conformational aspects ofnucleosides and nucleotides has been sufficiently documented (60-63).Of the two main aspects of CD studies, stereochemical and spectroscopic, the spectroscopic problem is currently the more fundamental because incomplete knowledge of the electronic transitions that give rise to the absorption of radiation and the rotatory power has limited attempts to determine optically the chirality of nucleosides. Along with difficulties associated with treating the weak perturbation effects of the nonchromophoric sugar, this incomplete knowledge has hindered the development of theoretical models for calculating the rotatory parameters and extracting stereochemical information from them. In spite of these problems, CD studies of nucleosides have produced some useful rules and diagrams relating the sign of the first CD band to anomeric configuration and to conformation (10, 31-41, 52-61).The major goal of this study is to use the experimental data on 3-deaza-4-deoxyuridine, 3-deazauridine, and 3-deazacytidine to evaluate a new theoretical method for calculating and interpreting the optical properties of nucleosides. The method uses wave functions of...

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Circular dichroism of nucleoside derivatives. IV. Uracil derivatives

Cited by 75 publications

References 6 publications

Calculations of the circular dichroism of adenosine derivatives constrained in the syn form

Calculations of the circular dichroism of adenosine derivatives constrained in the syn form

Characterization of the interaction of myosin with ATP analogues having the syn conformation with respect to the adenine‐ribose bond

Optical activity and electronic absorption spectra of some simple nucleosides related to cytidine and uridine: all-valence-shell molecular orbital calculations.

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