An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Duplexes of homo-DNA, a hexose analogue of DNA and autonomous pairing system, exhibit unusual con... more Duplexes of homo-DNA, a hexose analogue of DNA and autonomous pairing system, exhibit unusual conformational features, and in the crystal structure create a unique doublehelical supramolecular motif whose main characteristic is a handedness that is opposite to that of the underlying crystallographic symmetry.
Acta Crystallographica Section C-crystal Structure Communications, Nov 15, 1996
ABSTRACT The molecule of the title compound, [{(CH3)(2)CH}(2)-C6H3NSi(CH3)(2)](2), displays a fou... more ABSTRACT The molecule of the title compound, [{(CH3)(2)CH}(2)-C6H3NSi(CH3)(2)](2), displays a four-membered silicon-nitrogen ring system, with the Si2N2 ring exactly planar.
Reinvestigation of the brown alga Dictyota pardalis f. pseudohamata CRIBB led to the crystallizat... more Reinvestigation of the brown alga Dictyota pardalis f. pseudohamata CRIBB led to the crystallization of 1 and to the isolation of the two new dolabellane derivatives 2 and 3. X‐Ray analysis of 1 and 2, together with detailed 1D‐and 2D‐NMR studies on 2 and 3, allowed their structures to be elucidated as (1R*,3S*,7S*,11R*,4Z)‐dolabella‐4,8(17), 12(18)‐triene‐3,7‐diol (1), (1R*,3S*,4S*,7S*,8S*,11R*,14R*,12E)‐3,4:7,8‐diepoxydolabe11‐12‐ene‐14, 18‐diol (2), and (1R*,3S*,4S*,7S*,8S*,11R*,14R*)‐3,4:7,8‐diepoxy‐l,4,8,12,12‐pentamethylbicyclo[9. 3. 0]tetra‐decan‐14‐ol(3).
Acta Crystallographica Section D-biological Crystallography, Nov 1, 1999
The crystal structure of the reduced high-potential iron protein (HiPIP) from Chromatium vinosum ... more The crystal structure of the reduced high-potential iron protein (HiPIP) from Chromatium vinosum has been redetermined in a new orthorhombic crystal modification, and the structure of its H42Q mutant has been determined in orthorhombic (H42Q-1) and cubic (H42Q-2) modifications. The first two were solved by ab initio direct methods using data collected to atomic resolution (1.20 and 0.93 Å, respectively). The recombinant wild type (rc-WT) with two HiPIP molecules in the asymmetric unit has 1264 protein atoms and 335 solvent sites, and is the second largest structure reported so far that has been solved by pure direct methods. The solutions were obtained in a fully automated way and included more than 80% of the protein atoms. Restrained anisotropic refinement for rc-WT and H42Q-1 converged to R_1=\sum\big||F_o|-|F_c|\big|\big/\sum|F_o| of 12.0 and 13.6%, respectively [data with I>2\sigma(I)], and 12.8 and 15.5% (all data). H42Q-2 contains two molecules in the asymmetric unit and diffracted only to 2.6 Å. In both molecules of rc-WT and in the single unique molecule of H42Q-1 the [Fe4S4]2+ cluster dimensions are very similar and show a characteristic tetragonal distortion with four short Fe—S bonds along four approximately parallel cube edges, and eight long Fe—S bonds. The unique protein molecules in H42Q-2 and rc-WT are also very similar in other respects, except for the hydrogen bonding around the mutated residue that is at the surface of the protein, supporting the hypothesis that the difference in redox potentials at lower pH values is caused primarily by differences in the charge distribution near the surface of the protein rather than by structural differences in the cluster region.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Reactions of LnCl 3 (Ln) Nd, Gd, Yb) and [{Me 2 SiN(R)Li} 2 ] (R) t-Bu, Ph) give the chloride-bri... more Reactions of LnCl 3 (Ln) Nd, Gd, Yb) and [{Me 2 SiN(R)Li} 2 ] (R) t-Bu, Ph) give the chloride-bridged dimers [{{(t-Bu)NSiMe 2 SiMe 2 N(t-Bu)}Ln(µ-Cl)(THF)} 2 ] (1, Ln) Nd; 2, Ln) Gd; 3, Ln) Yb) and [{{(Ph)NSiMe 2-SiMe 2 N(Ph)}Ln(µ-Cl)(THF) 2 } 2 ] (4, Ln) Nd; 5, Ln) Gd; 6, Ln) Yb) in good yields. Compounds 2 and 5 were structurally characterized by X-ray crystallography: 2, triclinic, P1 h, a) 10.321(2) Å, b) 11.116(2) Å, c) 13.434(3) Å, R) 107.57(3)°,) 111.31(3)°, γ) 90.67(3)°, V) 1356.1(5) Å 3 , Z) 1, R) 0.0233; 5, monoclinic, P2 1 /n, a) 13.913(13) Å, b) 12.914(9) Å, c) 16.434(14) Å,) 105.64(3)°, V) 2843(4) Å 3 , Z) 2, R) 0.0281. The chloro functions in 1-6 remain reactive, demonstrated by the isolation of the trifluoroacetate derivatives of 1 and 2. Treatment of 1 or 2 with 2 equiv of NaOCOCF 3 gives [{{(t-Bu)NSiMe 2 SiMe 2 N(t-Bu)}-Ln(µ-OCOCF 3)(THF)} 2 ] (7, Ln) Nd; 8, Ln) Gd). The structure of 8 was determined by a single-crystal X-ray diffraction analysis. Crystal data for 8: triclinic, P1 h, a) 11.045(2) Å, b) 16.120(3) Å, c) 16.949(3) Å, R) 66.17(3)°,) 85.51(3)°, γ) 78.27(3)°, V) 2702.9(9) Å 3 , Z) 2, R) 0.0311. The structure of 8 shows the trifluoroacetate group adopting a bridging bidentate mode of coordination.
A conformational analysis of the (3′S,5′R)‐2′‐deoxy‐3′,5′‐ethano‐α‐D‐ribonucleosides (a‐D‐bicyclo... more A conformational analysis of the (3′S,5′R)‐2′‐deoxy‐3′,5′‐ethano‐α‐D‐ribonucleosides (a‐D‐bicyclodeoxynucleosides) based on the X‐ray analysis of N4‐benzoyl‐α‐D‐(bicyclodeoxycytidine) 6 and on 1H‐NMR analysis of the α‐D‐bicyclodeoxynucleoside derivatives 1‐7 reveals a rigid sugar structure with the furanose units in the l′‐exo/2′‐endo conformation and the secondary OH groups on the carbocyclic ring in the pseudoequatorial orientation. Oligonucleotides consisting of α‐D‐bicyclothymidine and α‐D‐bicyclodeoxyadenosine were successfully synthesized from the corresponding nucleosides by phosphoramidite methodology on a DNA synthesizer. An evaluation of their pairing properties with complementary natural RNA and DNA by means of UV/melting curves and CD spectroscopy show the following characteristics: i) α‐bcd(A10) and α‐bcd(T10) (α = short form of α‐D)efficiently form complexes with complementary natural DNA and RNA. The stability of these hybrids is comparable or slightly lower as those with natural β‐d(A10) or β‐d(T10)( β = short form ofβ‐D). ii) The strand orientation in α‐bicyclo‐DNA/β‐DNA duplexes is parallel as was deduced from UV/melting curves of decamers with nonsymmetric base sequences. iii) CD Spectroscopy shows significant structural differences between α‐bicyclo‐DNA/β‐DNA duplexes compared to α‐DNA/β‐DNA duplexes. Furthermore, α‐bicyclo‐DNA is ca. 100‐fold more resistant to the enzyme snake‐venom phosphodiesterase with respect to β‐DNA and about equally resistant as α‐DNA.
Time resolved and stationary fluorescence spectra of oxazine-4 perchlorate in 2-methyltetrahydrof... more Time resolved and stationary fluorescence spectra of oxazine-4 perchlorate in 2-methyltetrahydrofuran (2-MTHF) were measured from 80 to 250 K. In the time resolved experiments the relaxation of the polar solvent around the chromophore was observed. Assuming a simple Debye relaxation behavior, relaxation times were extracted and from an Arrhenius analysis an activation energy of E A-1320 cm-~ was estimated. The temperature dependent steady state fluorescence spectrum could be simulated using the obtained Arrhenius parameters• It was observed that exciting vibrational degrees of freedom in the chromophore leads to an acceleration of the solvent relaxation. As a probable reason a locally heating, caused by vibrational relaxation prior to the reorganization of the solvent shell is discussed.
The crystal structure of the duplex formed by oligo(2',3'-dideoxy-b-D-glucopyranosyl)nucleotides ... more The crystal structure of the duplex formed by oligo(2',3'-dideoxy-b-D-glucopyranosyl)nucleotides (homo-DNA) revealed strongly inclined backbone and base-pair axes [Egli,M.,
Homo-DNA ((49A69)-linked oligo-29,39-dideoxy-b-D-glucopyranose nucleic acid) constitutes the earl... more Homo-DNA ((49A69)-linked oligo-29,39-dideoxy-b-D-glucopyranose nucleic acid) constitutes the earliest synthetic model system whose pairing properties have been studied within an etiology of nucleic acid structure. Its conception as part of a program directed at a rationalization of Nature's selection of pentoses over other candidates as the carbohydrate building block in the genetic material was motivated by the question: why pentose and not hexose? Homo-DNA forms an autonomous pairing system and its duplexes are entropically stabilized relative to DNA duplexes. Moreover, the base pairing priorities in homo-DNA duplexes differ from those in DNA. A deeper understanding of the particular properties of homo-DNA requires knowledge of its structure. Although diffraction data for crystals of a homo-DNA octamer duplex were available to medium resolution in the mid-1990s, it took another decade for the structure to be solved. In this tutorial Review we describe the odyssey from the crystallization to the final structure determination with its many failures and disappointments and the development of selenium chemistry to derivatize nucleic acids for crystallographic phasing. More than fifty years after the discovery of the DNA double helix, the story of homo-DNA also provides a demonstration of the limits of theoretical models and offers a fresh view of fundamental issues in regard to the natural nucleic acids, such as the origins of antiparallel pairing and helicality.
The stability of hybrids of 2'-O-methylribonucleotides with complementary RNA is considerably hig... more The stability of hybrids of 2'-O-methylribonucleotides with complementary RNA is considerably higher than that of the corresponding DNA*RNA duplexes. The 2'-O-modified ribonucleotides are thus an attractive class of compounds for antisense applications. Understanding how these substituents stabilize the structure of the hybrid duplex may be important in the design of ribonucleotides with novel properties. Results: The crystal structure of a dimer of the selfcomplementary DNA strand d(GCGT)02'm"r(A)d(TACGC), which has a 2'-0-methylated ribonucleotide incorporated at position 5, was determined at 2.1 A resolution. This strand forms a duplex with an overall A-type conformation; the methyl groups of the two modified adenosines point into the relatively wide minor groove. Both 2'-methoxy groups are hydrogen-bonded to solvent molecules. These results allowed us to build a model of a fully 2'-0-methylated RNA double helix. Conclusions: Insertion of 2'-O-modified RNA residues into a stretch of DNA can nucleate a local A-type conformation, in part because modification with a bulky residue at this position stabilizes a C3'4nda type sugar pucker. The increased stability of fully 2'-0-methylated RNA may result from hydrophobic interactions between substituents in the minor groove. As the 2'-O-methyl groups are directed into the minor groove, it may be worthwhile to introduce tailor-made 2'-0-substituents into RNA; it might be possible to design groups that both stabilize the hybrid duplexes and carry a nuclease function, further improving the efficacy of these modified RNAs in antisense applications.
Time correlated single photon counting was used to investigate solvent dynamics of laser dyes in ... more Time correlated single photon counting was used to investigate solvent dynamics of laser dyes in a polar, viscous solvent. The resolved total luminescence spectra of oxazine 4 in 2-methyitetrahydrofuran (2-MTHF) have been measured and solvent relaxation observed.
Acta Crystallographica Section D-biological Crystallography, Jun 1, 2000
The crystal structure of mersacidin, a potential novel antibiotic against methicillin- and vancom... more The crystal structure of mersacidin, a potential novel antibiotic against methicillin- and vancomycin-resistant Staphylococcus aureus strains, has been determined by ab initio methods. Despite all crystals being merohedrally twinned, an accurate structural model with an R value of 13.4% has been obtained at atomic resolution. With six molecules in the asymmetric unit and no atom heavier than sulfur, the structure corresponds to a protein of 120 amino acids and is the largest approximately equal-atom unknown structure solved by direct methods. In the crystal, the molecule assumes a compact fold different from that found by NMR in solution. Comparison of the NCS-related molecules reveals regions of variable flexibility. The region highly homologous to the related antibiotic actagardine is very rigid and possibly defines an essential building block of this class of new antibacterial substances.
Using a conceptual framework based a) on a model where energy is the regulating agent and b) on t... more Using a conceptual framework based a) on a model where energy is the regulating agent and b) on the introduction of conjugated intensive and extensive quantities, together with the introduction from the beginning of the concepts of entropy and chemical potential allows to coherently model a variety of situations relating to didactically interesting examples referring to different disciplines.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Duplexes of homo-DNA, a hexose analogue of DNA and autonomous pairing system, exhibit unusual con... more Duplexes of homo-DNA, a hexose analogue of DNA and autonomous pairing system, exhibit unusual conformational features, and in the crystal structure create a unique doublehelical supramolecular motif whose main characteristic is a handedness that is opposite to that of the underlying crystallographic symmetry.
Acta Crystallographica Section C-crystal Structure Communications, Nov 15, 1996
ABSTRACT The molecule of the title compound, [{(CH3)(2)CH}(2)-C6H3NSi(CH3)(2)](2), displays a fou... more ABSTRACT The molecule of the title compound, [{(CH3)(2)CH}(2)-C6H3NSi(CH3)(2)](2), displays a four-membered silicon-nitrogen ring system, with the Si2N2 ring exactly planar.
Reinvestigation of the brown alga Dictyota pardalis f. pseudohamata CRIBB led to the crystallizat... more Reinvestigation of the brown alga Dictyota pardalis f. pseudohamata CRIBB led to the crystallization of 1 and to the isolation of the two new dolabellane derivatives 2 and 3. X‐Ray analysis of 1 and 2, together with detailed 1D‐and 2D‐NMR studies on 2 and 3, allowed their structures to be elucidated as (1R*,3S*,7S*,11R*,4Z)‐dolabella‐4,8(17), 12(18)‐triene‐3,7‐diol (1), (1R*,3S*,4S*,7S*,8S*,11R*,14R*,12E)‐3,4:7,8‐diepoxydolabe11‐12‐ene‐14, 18‐diol (2), and (1R*,3S*,4S*,7S*,8S*,11R*,14R*)‐3,4:7,8‐diepoxy‐l,4,8,12,12‐pentamethylbicyclo[9. 3. 0]tetra‐decan‐14‐ol(3).
Acta Crystallographica Section D-biological Crystallography, Nov 1, 1999
The crystal structure of the reduced high-potential iron protein (HiPIP) from Chromatium vinosum ... more The crystal structure of the reduced high-potential iron protein (HiPIP) from Chromatium vinosum has been redetermined in a new orthorhombic crystal modification, and the structure of its H42Q mutant has been determined in orthorhombic (H42Q-1) and cubic (H42Q-2) modifications. The first two were solved by ab initio direct methods using data collected to atomic resolution (1.20 and 0.93 Å, respectively). The recombinant wild type (rc-WT) with two HiPIP molecules in the asymmetric unit has 1264 protein atoms and 335 solvent sites, and is the second largest structure reported so far that has been solved by pure direct methods. The solutions were obtained in a fully automated way and included more than 80% of the protein atoms. Restrained anisotropic refinement for rc-WT and H42Q-1 converged to R_1=\sum\big||F_o|-|F_c|\big|\big/\sum|F_o| of 12.0 and 13.6%, respectively [data with I>2\sigma(I)], and 12.8 and 15.5% (all data). H42Q-2 contains two molecules in the asymmetric unit and diffracted only to 2.6 Å. In both molecules of rc-WT and in the single unique molecule of H42Q-1 the [Fe4S4]2+ cluster dimensions are very similar and show a characteristic tetragonal distortion with four short Fe—S bonds along four approximately parallel cube edges, and eight long Fe—S bonds. The unique protein molecules in H42Q-2 and rc-WT are also very similar in other respects, except for the hydrogen bonding around the mutated residue that is at the surface of the protein, supporting the hypothesis that the difference in redox potentials at lower pH values is caused primarily by differences in the charge distribution near the surface of the protein rather than by structural differences in the cluster region.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Reactions of LnCl 3 (Ln) Nd, Gd, Yb) and [{Me 2 SiN(R)Li} 2 ] (R) t-Bu, Ph) give the chloride-bri... more Reactions of LnCl 3 (Ln) Nd, Gd, Yb) and [{Me 2 SiN(R)Li} 2 ] (R) t-Bu, Ph) give the chloride-bridged dimers [{{(t-Bu)NSiMe 2 SiMe 2 N(t-Bu)}Ln(µ-Cl)(THF)} 2 ] (1, Ln) Nd; 2, Ln) Gd; 3, Ln) Yb) and [{{(Ph)NSiMe 2-SiMe 2 N(Ph)}Ln(µ-Cl)(THF) 2 } 2 ] (4, Ln) Nd; 5, Ln) Gd; 6, Ln) Yb) in good yields. Compounds 2 and 5 were structurally characterized by X-ray crystallography: 2, triclinic, P1 h, a) 10.321(2) Å, b) 11.116(2) Å, c) 13.434(3) Å, R) 107.57(3)°,) 111.31(3)°, γ) 90.67(3)°, V) 1356.1(5) Å 3 , Z) 1, R) 0.0233; 5, monoclinic, P2 1 /n, a) 13.913(13) Å, b) 12.914(9) Å, c) 16.434(14) Å,) 105.64(3)°, V) 2843(4) Å 3 , Z) 2, R) 0.0281. The chloro functions in 1-6 remain reactive, demonstrated by the isolation of the trifluoroacetate derivatives of 1 and 2. Treatment of 1 or 2 with 2 equiv of NaOCOCF 3 gives [{{(t-Bu)NSiMe 2 SiMe 2 N(t-Bu)}-Ln(µ-OCOCF 3)(THF)} 2 ] (7, Ln) Nd; 8, Ln) Gd). The structure of 8 was determined by a single-crystal X-ray diffraction analysis. Crystal data for 8: triclinic, P1 h, a) 11.045(2) Å, b) 16.120(3) Å, c) 16.949(3) Å, R) 66.17(3)°,) 85.51(3)°, γ) 78.27(3)°, V) 2702.9(9) Å 3 , Z) 2, R) 0.0311. The structure of 8 shows the trifluoroacetate group adopting a bridging bidentate mode of coordination.
A conformational analysis of the (3′S,5′R)‐2′‐deoxy‐3′,5′‐ethano‐α‐D‐ribonucleosides (a‐D‐bicyclo... more A conformational analysis of the (3′S,5′R)‐2′‐deoxy‐3′,5′‐ethano‐α‐D‐ribonucleosides (a‐D‐bicyclodeoxynucleosides) based on the X‐ray analysis of N4‐benzoyl‐α‐D‐(bicyclodeoxycytidine) 6 and on 1H‐NMR analysis of the α‐D‐bicyclodeoxynucleoside derivatives 1‐7 reveals a rigid sugar structure with the furanose units in the l′‐exo/2′‐endo conformation and the secondary OH groups on the carbocyclic ring in the pseudoequatorial orientation. Oligonucleotides consisting of α‐D‐bicyclothymidine and α‐D‐bicyclodeoxyadenosine were successfully synthesized from the corresponding nucleosides by phosphoramidite methodology on a DNA synthesizer. An evaluation of their pairing properties with complementary natural RNA and DNA by means of UV/melting curves and CD spectroscopy show the following characteristics: i) α‐bcd(A10) and α‐bcd(T10) (α = short form of α‐D)efficiently form complexes with complementary natural DNA and RNA. The stability of these hybrids is comparable or slightly lower as those with natural β‐d(A10) or β‐d(T10)( β = short form ofβ‐D). ii) The strand orientation in α‐bicyclo‐DNA/β‐DNA duplexes is parallel as was deduced from UV/melting curves of decamers with nonsymmetric base sequences. iii) CD Spectroscopy shows significant structural differences between α‐bicyclo‐DNA/β‐DNA duplexes compared to α‐DNA/β‐DNA duplexes. Furthermore, α‐bicyclo‐DNA is ca. 100‐fold more resistant to the enzyme snake‐venom phosphodiesterase with respect to β‐DNA and about equally resistant as α‐DNA.
Time resolved and stationary fluorescence spectra of oxazine-4 perchlorate in 2-methyltetrahydrof... more Time resolved and stationary fluorescence spectra of oxazine-4 perchlorate in 2-methyltetrahydrofuran (2-MTHF) were measured from 80 to 250 K. In the time resolved experiments the relaxation of the polar solvent around the chromophore was observed. Assuming a simple Debye relaxation behavior, relaxation times were extracted and from an Arrhenius analysis an activation energy of E A-1320 cm-~ was estimated. The temperature dependent steady state fluorescence spectrum could be simulated using the obtained Arrhenius parameters• It was observed that exciting vibrational degrees of freedom in the chromophore leads to an acceleration of the solvent relaxation. As a probable reason a locally heating, caused by vibrational relaxation prior to the reorganization of the solvent shell is discussed.
The crystal structure of the duplex formed by oligo(2',3'-dideoxy-b-D-glucopyranosyl)nucleotides ... more The crystal structure of the duplex formed by oligo(2',3'-dideoxy-b-D-glucopyranosyl)nucleotides (homo-DNA) revealed strongly inclined backbone and base-pair axes [Egli,M.,
Homo-DNA ((49A69)-linked oligo-29,39-dideoxy-b-D-glucopyranose nucleic acid) constitutes the earl... more Homo-DNA ((49A69)-linked oligo-29,39-dideoxy-b-D-glucopyranose nucleic acid) constitutes the earliest synthetic model system whose pairing properties have been studied within an etiology of nucleic acid structure. Its conception as part of a program directed at a rationalization of Nature's selection of pentoses over other candidates as the carbohydrate building block in the genetic material was motivated by the question: why pentose and not hexose? Homo-DNA forms an autonomous pairing system and its duplexes are entropically stabilized relative to DNA duplexes. Moreover, the base pairing priorities in homo-DNA duplexes differ from those in DNA. A deeper understanding of the particular properties of homo-DNA requires knowledge of its structure. Although diffraction data for crystals of a homo-DNA octamer duplex were available to medium resolution in the mid-1990s, it took another decade for the structure to be solved. In this tutorial Review we describe the odyssey from the crystallization to the final structure determination with its many failures and disappointments and the development of selenium chemistry to derivatize nucleic acids for crystallographic phasing. More than fifty years after the discovery of the DNA double helix, the story of homo-DNA also provides a demonstration of the limits of theoretical models and offers a fresh view of fundamental issues in regard to the natural nucleic acids, such as the origins of antiparallel pairing and helicality.
The stability of hybrids of 2'-O-methylribonucleotides with complementary RNA is considerably hig... more The stability of hybrids of 2'-O-methylribonucleotides with complementary RNA is considerably higher than that of the corresponding DNA*RNA duplexes. The 2'-O-modified ribonucleotides are thus an attractive class of compounds for antisense applications. Understanding how these substituents stabilize the structure of the hybrid duplex may be important in the design of ribonucleotides with novel properties. Results: The crystal structure of a dimer of the selfcomplementary DNA strand d(GCGT)02'm"r(A)d(TACGC), which has a 2'-0-methylated ribonucleotide incorporated at position 5, was determined at 2.1 A resolution. This strand forms a duplex with an overall A-type conformation; the methyl groups of the two modified adenosines point into the relatively wide minor groove. Both 2'-methoxy groups are hydrogen-bonded to solvent molecules. These results allowed us to build a model of a fully 2'-0-methylated RNA double helix. Conclusions: Insertion of 2'-O-modified RNA residues into a stretch of DNA can nucleate a local A-type conformation, in part because modification with a bulky residue at this position stabilizes a C3'4nda type sugar pucker. The increased stability of fully 2'-0-methylated RNA may result from hydrophobic interactions between substituents in the minor groove. As the 2'-O-methyl groups are directed into the minor groove, it may be worthwhile to introduce tailor-made 2'-0-substituents into RNA; it might be possible to design groups that both stabilize the hybrid duplexes and carry a nuclease function, further improving the efficacy of these modified RNAs in antisense applications.
Time correlated single photon counting was used to investigate solvent dynamics of laser dyes in ... more Time correlated single photon counting was used to investigate solvent dynamics of laser dyes in a polar, viscous solvent. The resolved total luminescence spectra of oxazine 4 in 2-methyitetrahydrofuran (2-MTHF) have been measured and solvent relaxation observed.
Acta Crystallographica Section D-biological Crystallography, Jun 1, 2000
The crystal structure of mersacidin, a potential novel antibiotic against methicillin- and vancom... more The crystal structure of mersacidin, a potential novel antibiotic against methicillin- and vancomycin-resistant Staphylococcus aureus strains, has been determined by ab initio methods. Despite all crystals being merohedrally twinned, an accurate structural model with an R value of 13.4% has been obtained at atomic resolution. With six molecules in the asymmetric unit and no atom heavier than sulfur, the structure corresponds to a protein of 120 amino acids and is the largest approximately equal-atom unknown structure solved by direct methods. In the crystal, the molecule assumes a compact fold different from that found by NMR in solution. Comparison of the NCS-related molecules reveals regions of variable flexibility. The region highly homologous to the related antibiotic actagardine is very rigid and possibly defines an essential building block of this class of new antibacterial substances.
Using a conceptual framework based a) on a model where energy is the regulating agent and b) on t... more Using a conceptual framework based a) on a model where energy is the regulating agent and b) on the introduction of conjugated intensive and extensive quantities, together with the introduction from the beginning of the concepts of entropy and chemical potential allows to coherently model a variety of situations relating to didactically interesting examples referring to different disciplines.
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