Design of peptides: synthesis, crystal structure, molecular conformation, and conformational calculations of N-Boc-L-Phe-Dehydro-Ala-OCH3.

It is noteworthy that the dehydro-Ala residue adopts an extended conformation that is different than those observed in dehydro-Phe, dehydro-Leu, and dehydro-Abu. The peptide N-Boc-L-Phe-dehydro-Ala-OCH3 (C18H24N2O5) was synthesized by the usual workup procedure and finally by converting N-Boc-L-Phe-L-Ser-OCH3 to N-Boc-L-Phe-dehydro-Ala- OCH3. It was crystallized from its solution in a methanol-water mixture at room temperature. The crystals belong to the monoclonic space group P2(1), with a = 9.577(1) A, b = 5.195(3) A, c = 19.563(3) A, beta = 94.67(5) degrees, V = 970.1(6) A3, Z = 2, dm = 1.201(5) Mg m-3, dc = 1.197(5) Mg m-3. The structure was determined using direct method procedures. It was refined by a full-matrix least-squares procedure to an R value of 0.048 for 1370 observed reflections. The C2 alpha-C2 beta distance is 1.327(8) A, while the bond angles N2-C2 alpha-C2' and C1'-N2-C2 alpha are 109.8(5) degrees and 127.8(5) degrees, respectively. The backbone adopts a nonspecific conformation with dehydro-Ala in a fully extended conformation with the following torsion angles: theta 1 = 175.2(4) degrees, omega 0 = 170.2(4) degrees, phi 1 = 135.8(5) degrees, psi 1 = -22.6(6) degrees, omega 1 = 168.5(5) degrees, phi 2 = -170.3(5) degrees, psi 2T = -178.6(5) degrees, theta T = 178.4(7) degrees. The rigid planar and trans conformation of dehydro-Ala forces Phe to adopt a strained conformation. The Boc group has a trans-trans conformation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Crystal-state structural analysis of two gamma-lactam-restricted analogs of Pro-Leu-Gly-NH2

The crystal structures of two analogs of Pro-Leu-Gly-NH2 (1), containing a gamma-lactam conformational constraint in place of the -Leu-Gly- sequences, are described. The highly biologically active (S,R)-diastereomer 2a is semi-extended at the C-terminus, with the N-terminal Pro residue in the unusual "C5" conformation [psi 1 = -0.8(15) degrees] stabilized by a (peptide)N-H...N(amino) intramolecular H-bond [the N(3)...N(4) separation is 2.687(11)A]. Conversely, the N,N'-isopropylidene aminal trihydrate of the (S,S)-diastereomer 2b, compound 3, adopts a beta-bend conformation at the C-terminus, as already reported for 1. However, the backbone torsion angles [phi 2 = 57.4(4), psi 2 = -129.9(3) degrees; psi 3 = -92.3(4), phi 3 = 6.4(5) degrees] lie close to the values expected for the corner residues of an ideal type-II' beta-bend. A weak intramolecular 4----1 H-bond is seen between the Gly carboxyamide anti-NH and Pro C = O groups. In the newly formed 2,2,3,4-tetraalkyl-5-oxo-imidazolidin-1-yl moiety the psi 1 torsion angle is 12.9(4) degrees and the intramolecular N(3)...N(4) separation is 2.321(4)A.     

Structure and conformation of 1-beta-D-ribo furanosyl pyridin-2-one-5-carboxamide: an anti-inflammatory agent

The pyrimidine nucleoside, 1-beta-D-ribofuranosyl pyridine-2-one-5-carboxamide, is an anti inflammatory agent used in the treatment of adjuvant-induced arthritis. It is the 2-one isomer of 1-beta-D-ribofuranosyl pyridine-4-one 5-carboxamide, an unusual nucleoside isolated from the urine of patients with chronic myelogenic leukemia and an important cancer marker. Crystals of 1-beta-D-ribofuranosyl pyridine-2-one-5-carboxamide are monoclinic, space group C2, with the cell dimensions a = 31.7920(13), b = 4.6872 (3), c = 16.1838(11), beta = 93.071(3) degrees , V = 2408.2(2) A(3), D(calc) = 1.496 mg/m(3) and Z = 8 (two molecules in the asymmetric unit). The structure was obtained by the application of direct methods to diffractometric data and refined to a final R value of 0.050 for 1669 reflections with I >or= 3sigma. The nucleoside exhibits an anti conformation across the glycosidic bond (chi(CN) = -15.5 degrees , -18.9 degrees ), a C3 '-endo C2 '-exo [(3)(2)T] ribose pucker and g(+) across the C(4 ')-C(5 ') exocyclic bond. The amino group of the carboxamide group is distal from the 2-one and lacks the intramolecular hydrogen bonding found in the related 2-one molecule. Nuclear magnetic resonance studies shows also an anti conformation across the glycosidic bond but the solution conformation of the furanose ring is not the same as that found in the solid state.     

Synthesis, crystal structure, and molecular conformation of peptide N-Boc-L-Pro-dehydro-Phe-L-Gly-OH

The peptide N-Boc-L-Pro-dehydro-Phe-L-Gly-OH was synthesized by the usual workup procedure and finally coupling the N-Boc-L-Pro-dehydro-Phe to glycine. The peptide crystallizes in monoclinic space group P2(1) with a = 8.951(4) A, b = 5.677(6) A, c = 21.192(11) A, beta = 96.97(4) degrees, V = 1069(1) A3, Z = 2, dm = 1.295(5) Mgm-3, and dc = 1.297(4) Mgm-3. The structure was determined by direct methods using SHELXS86. The structure was refined by the block-diagonal least-squares procedure to an R value of 0.074 for 1002 observed reflections. The C alpha 2-C beta 2 distance of 1.33(2) A is an appropriate double bond length. The angle C alpha 2-C beta 2-C gamma 2 is 133(1) degrees. The peptide backbone torsion angles are theta 1 = -167(1) degrees, omega 0 = 179(1) degrees, phi 1 = -48(1) degrees, psi 1 = 137(1) degrees, omega 1 = 175(1) degrees, phi 2 = 65(2) degrees, psi 2 = 15(2) degrees, omega 2 = -179(1) degrees, and phi 3 = -166(1) degrees. These values show that the Boc group has a trans-trans conformation while the peptide backbone adopts a beta-turn II conformation, which is stabilized by an intramolecular hydrogen bond of length of 3.05(1) A. The structures of dehydro-Phe containing peptides suggest that the dehydro-Phe promotes the beta-turn II conformation. The five-membered pyrrolidine ring of the Pro residue adopts an ideal C gamma-exo conformation with torsion angles chi 1(1) = -24(1) degrees, chi 2(1) = 34(1) degrees, chi 3(1) = -30(1) degrees, chi 4(1) = 15(1) degrees, and theta 0(1) = 6(1) degrees. The side-chain torsion angles in dehydro-Phe are chi 1(2) = -1(2) degrees, chi 2,1(2) = -176(1) degrees, and chi 2,2(2) = 8(2) degrees. The plane of C alpha 2-C beta 2-C gamma 2 is rotated with respect to the plane of the phenyl ring at 7(1) degrees, which indicates that the atoms of the side chain of dehydro-Phe are essentially coplanar. The molecules form a 2(1) screw axis related hydrogen-bonded rows along the b axis.     

Synthesis, crystal structure, and molecular conformation of N-Ac-dehydro-Phe-L-Val-L-Val-OCH3.

The peptide N-Ac-dehydro-Phe-L-Val-L-Val-OCH3 (C22H31N3O5) was synthesized by the usual workup procedure and finally by coupling the N-Ac-dehydro-Phe-L-Val-OH to valine methyl ester. It was crystallized from its solution in acetonitrile-water mixture at 4 degrees C. The crystals belong to the space group P1 with a = 8.900(3) A, b = 11.135(2) A, c = 12.918(2) A, alpha = 90.36(1) degrees, beta = 110.14(3) 14(3) degrees, V = 1207.7(6) A, 3Z = 2, dm = 1.156(5) Mgm-3, dc = 1.148(5) Mgm-3. The structure was determined by direct methods using SHELXS86. The structure was refined by full-matrix least-squares procedure to an R value of 0.077 for 3916 observed reflections. The molecular dimensions and conformations of the two crystallographically independent molecules are in good agreement. In the dehydro residues, the average C alpha-C beta distance is 1.31(2) A whereas the bond angle C alpha-C beta-C gamma is 132(1) degrees. The average backbone torsion angles are omega 0 = 169(1) degrees, phi 1 = -40(1) degree, psi 1 = -50(1) degree, omega 1 = -177(1) degree, phi 2 = 54(1) degree, psi 2 = 46(1) degree, omega 2 = -174(1) degree, phi 3 = 103(1) degree, psi T3 = -139(1) degree, and theta T3 = -176(1) degree. The acetyl group is in the trans conformation, while the backbone adopts a right-handed and left-handed helical conformation alternatingly.(ABSTRACT TRUNCATED AT 250 WORDS)     

6-Azauridine, a nucleoside with unusual ribose conformation. The molecular and crystal structure

The cytostatic analogue ribo-6-azauridine crystallizes in the orthorhombic space group P2₁2₁2₁ with eight molecules per unit cell of dimensions $\text{a = 20.230, b = 7.709, c = 12.863}\text{A}\text{?}$. A trial structure was obtained by direct methods. Least-squares refinement of co-ordinates and anisotropic thermal parameters based on 1998 reflections measured on a four-circle diffractometer led to a discrepancy index R = 4.0%. Like uridine, 6-azauridine has the anti conformation about the glycosidic bond and a C(3′)-endo sugar pucker. Unlike uridine, it exhibits a close approach of N(6) to C(2′) at only 2.814 and 2.844 Å in the two independent molecules, and a C(5′)(5′) bond that is gauche to C(4′)O(1′) but trans to C(4′)C(3′); this conformation about a C(4′)C(5′) bond has never been observed before for C(3′)-endo puckered riboses in the crystalline state. The crystal structure displays a pseudo-A face centering and very similar conformational parameters for the two independent molecules. Every OH and NH group in the structure serves as a proton donor in a hydrogen bond, including an unusual N(3)—H(3) … O(1′) link. Molecular orbital calculations by the extended Hückel method indicate that from uridine to 6-azauridine the net charge changes sign at ring positions 5 and 6 and disappears at 1.     

Structural and conformational analysis of pentostatin (2'-deoxycoformycin), a potent inhibitor of adenosine deaminase

X-ray, NMR and molecular mechanics studies on pentostatin (C11H16N4O4), a potent inhibitor of the enzyme adenosine deaminase, have been carried out to study the structure and conformation. The crystals belong to the monoclinic space group P21 with the cell dimensions of a = 4.960(1), b = 10.746(3), c = 11.279(4)A, beta = 101.18(2) degrees and Z = 2. The structure was solved by direct methods and difference Fourier methods and refined to an R value of 0.047 for 997 reflections. The trihydrodiazepine ring is nonplanar and adopts a distorted sofa conformation with C(7) deviated from the mean plane by 0.66A. The deoxyribose ring adopts a C3'-endo conformation, different from coformycin where the sugar has a C2'-endo conformation. The observed glycosidic torsion angle (chi = -119.5 degrees) is in the anti range. The conformation about the C(4')-C(5') bond is gauche+. The conformation of the molecule is compared with that of coformycin and 2-azacoformycin. 1 and 2D NMR studies have been carried out and the dihedral angles obtained from coupling constants have been compared with those obtained from the crystal structure. The conformation of deoxyribose in solution is approximately 70% S and 30% N. Molecular mechanics studies were performed to obtain the energy minimized conformation, which is compared with X-ray and NMR results.     

Synthesis, crystal structure and molecular conformation of N-Ac-dehydro-Phe-L-Val-OH.

The peptide N-Ac-dehydro-Phe-L-Val-OH (C16H20N2O4) was synthesized by the usual workup procedure. The peptide crystallizes from its solution in acetonitrile at 4 degrees in hexagonal space group P6(5) with a = b = 11.874(2)A, c = 21.856(9) A, V = 2668(1) A3, Z = 6, dm = 1.151(3) g cm-3, dc = 1.136(4) g cm-3, CuK alpha = 1.5418 A, mu = 0.641 mm-1, F(000) = 972, T = 293 K. The structure was solved by direct methods and refined by least-squares procedure to an R value of 0.074 for 1922 observed reflections. In the dehydro-residue, the C1 alpha-C1 beta distance is 1.35(1) A while the bond angle C1 alpha-C1 beta-C1 gamma is 131.2(9) degrees. The backbone torsion angles are: omega 0 = 172(1) degrees, phi 1 = -60(2) degrees, psi 1 = -31(2) degrees, omega 1 = -179(1) degrees, phi 2 = 59(2) degrees. These values suggest that the peptide tends to adopt an alternating right-handed and left-handed helical conformation. The side chain torsion angles are: chi 1(1) = -6(2) degrees, chi 1(2.1) = -1(2) degrees, chi 1(2.2) = -178(2) degrees, chi 2(1.1) = 63(2) degrees and chi 2(1.2) = -173(1) degrees. These values show that the side chain of dehydro-Phe is planar whereas the valyl side chain adopts a sterically most preferred conformation. The molecules, linked by intermolecular hydrogen bonds and van der Waals forces, are arranged in helices along the c-axis. The helices are held side-by-side by van der Waals contacts.     

Crystal structure and conformation of 8-(2-hydroxyethylamino) and 8-(pyrrolidin-1-yl) adenosines

In the course of investigation of 8-alkylamino substituted adenosines, the title compounds were synthesized as potential partial agonists for adenosine receptors. The structure determination of these compounds was carried out with the X-ray crystallography study. Crystals of 8-(2-hydroxyethylamino)adenosine are monoclinic, space group P 2(1); a = 7.0422(2), b = 11.2635(3), c = 8.9215(2) A, beta = 92.261(1) degrees, V = 707.10(3) A3, Z = 2; R-factor is 0.0339. The nucleoside is characterized by the anti conformation; the ribose ring has the C(2')-endo conformation and gauche-gauche form across C(4')-C(5') bond. The molecular structure is stabilized by intramolecular hydrogen bond of N-HO type. Crystals of 8-(pyrrolidin-1-yl)adenosine are monoclinic, space group C 2; a = 19.271(1), b = 7.3572(4), c = 11.0465(7) A, beta = 103.254(2), V = 1524.4(2) degrees A3, Z = 4; R-factor is 0.0498. In this compound, there is syn conformation of the nucleoside; the ribose has the C(2')-endo conformation and gauche -gauche form across C(4')- C(5') bond. The molecular structure is stabilized by intramolecular hydrogen bond of O-HN type. For both compounds, the branching net of intermolecular hydrogen bonds occur in the crystal structures.     

Crystal structure of the promutagen O4-methylthymidine: importance of the anti conformation of the O(4) methoxy group and possible mispairing of O4-methylthymidine with guanine

O4-Methylthymidine (O4medT) is a promutagen. To correlate its biological properties to changes in the electronic, geometric, and conformational properties of the pyrimidine base resulting from the keto to enol shift arising from methylation, an X-ray study of O4medT was undertaken. The crystal data are a = 4.950 (2) A, b = 12.648 (1) A, c = 19.305 (2) A, space group P2(1)2(1)2(1), Z = 4, and R = 0.042. The D-deoxyribofuranosyl ring is puckered in the uncommon 1T2 twist conformation with the phase angle of pseudorotation P = 133.8 (5)degrees. The amplitude of puckering tau m = 31.4 (3)degrees shows that the ring is considerably flattened. The base is in the anti conformation [chi CN = 40.6 (4)degrees], and the exocyclic C(4')-C(5') bond (psi) is gauche+ [46.2 (5)degrees]. Methylation produces cytosine-like conjugation for the thymine base. The methoxy group takes the syn-periplanar conformation. Two types of mispairings with guanine are possible, and both require the anti conformation for the O(4) methoxy group. Semiempirical energy calculations have been carried out and reveal that the anti conformation can be energetically assumed in the double helix by widening the exocyclic angles C(5)-C(4)-O(4) and C(4)-C(5)-C(7) and the angle C(4)-O(4)-C(8) at the methoxy group. Such coordinated expansion relieves unfavorable interactions between the C(7) and C(8) methyl groups.     

Crystal Structure and Molecular Conformation of 4-Thiouracil-2′-Trifluorothioacetamide -3′, 5′-Diacetyl-β-D-Riboside

Abstract

4-thiouracil-2′-trifluorothioacetamide-3′, 5′-diacetyl-β-D-riboside is one of the modified thiouracil analogs synthesized in our institute. The determination of the crystal and molecular structure of this compound was carried out with a view to study the conformation of the molecule in the solid state as well as to investigate the conformations of the trifluoroacetamide and the acetyl substituents of the ribose and their effects on the conformation of the ribose ring. Crystals of 4-thiouracil-2′-trifluorothioacetamide-3′,5′- diacetyl-β-D-riboside are orthorhombic, space group P2₁ 2₁ 2₁, with cell dimensions a= 15.351 (2), b= 15.535 (1), c= 8.307 (1) Å, V=1981.0 (7) ų, Z=4, D_m= 1.53, D_c=1.527 g/c.c. and μ=30.1cm -¹. The structure was determined using CuKα (λ, =1.5418 Å) at a temperature T of 297K, with 2333 reflections, which were collected on a Enraf-Nonius CAD-4 diffactometer, out of which 2249 (I ≥20) were considered observed. The structure was determined by direct methods using MULTAN and refined by full matrix least squares method to a final reliability factor of 0.054 and a weighted R factor of 0.079. The nucleoside is in the anti conformation [X_CN =51.4 (5)°], the ribose has the unusual C (2′) endo -C (1′) exo (²T₁), and a g+ conformation [ψ=47.5 (4)] across C(4′)-C(5′) bond. The pseudorotation angle P is 152.8 (4) ° and the amplitude of pucker τ_m of 42.7 (3)°. The average C-F bond distance is 1.308 Å. There is no base pairing and the typical base-base hydrogen bonded interactions are not present in this structure. On the other hand, a hydrogen bonded dimer is formed involving C(3′) - H(3′)… O (2) and N(3) -H (N3) … O (Al) hydrogen bonds joining the base, ribose ring and the acetyl group. The trend towards longer exocyclic bonds at the acetyl centers in compounds with strongly electronegative aglycones, is also exhibited in this compound, with C(3′)-O(3′) and C(5′)-0(5′) being much longer than C(1′)-O(4′). The acetyl groups also take part in C-H…O hydrogen bonding with the acetyl oxygen atom OA2.     

Crystal structure and conformation of 5-fluorouridine: conformational preferences for 5-fluorinated pyranosides

Crystals of 5-fluorouridine (5FUrd) have unit cell dimensions a = 7.716(1), b = 5.861(2), c = 13.041(1)A, alpha = gamma = 90 degrees, beta = 96.70 degrees (1), space group P2(1), Z = 2, rho obs = 1.56 gm/c.c and rho calc = 1574 gm/c.c The crystal structure was determined with diffractometric data and refined to a final reliability index of 0.042 for the observed 2205 reflections (I > or = 3sigma). The nucleoside has the anti conformation [chi = 53.1(4) degrees] with the furanose ring in the favorite C2'-endo conformation. The conformation across the sugar exocyclic bond is g+, with values of 49.1(4) and -69.3(4) degrees for phi(theta c) and phi (infinity) respectively. The pseudorotational amplitude tau(m) is 34.5 (2) with a phase angle of 171.6(4) degrees. The crystal structure is stabilized by a network of N-H...O and O-H...O involving the N3 of the uracil base and the sugar 03' and 02' as donors and the 02 and 04 of the uracil base and 03' oxygen as acceptors respectively. Fluorine is neither involved in the hydrogen bonding nor in the stacking interactions. Our studies of several 5-fluorinated nucleosides show the following preferred conformational features: 1) the most favored anti conformation for the nucleoside [chi varies from -20 to + 60 degrees] 2) an inverse correlation between the glycosyl bond distance and the chi angle 3) a wide variation of conformations of the sugar ranging froni C2'-endo through C3'-endo to C4'-exo 4) the preferred g+ across the exocyclic C4'-C5' bond and 5) no role for the fluorine atom in the hydrogen bonding or base stacking interactions.     

Crystal Structure of a Tightly Bound Inhibitor of Adenosine Transport N6-(4-Nitrobenzyl)-β-D-2′-Deoxyadenosine Methanol Solvate,C17H18N6O5.1/2 CH3OH

Abstract

The molecular structure of N⁶-(4-nitrobenzyl)-β-D-2′-deoxyadenosine (I) has been determined by single crystal X-ray diffraction. A potent inhibitor of adenosine permeation in cultured S49 mouse lymphoma cells, I binds tightly (K_D 2.4 nM) to high affinity membrane sites present on the nucleoside transporter elements of these cells. Compound I crystallizes in the trigonal space group P3₂21 with unit cell dimensions a = b = 8.0009(9)Å, c = 49.174(8)Å, and Z = 6. The structure was solved by direct methods and refined by least-squares to a final R = 0.038. The mean plane of the 4-nitrobenzyl group, an important substituent for potent nucleoside transport inhibition in a series of S6-substituted 6-thioinosine derivatives, is inclined at an angle of 120.6° to the plane of the adenine ring. The torsion angles around the methylene carbon atom of this benzyl group are C(6)-N(6)-C(10)-C(11), 96.6° and N(6)-C(10)-C(11)-C(12), 93.6°. The glycosidic torsion angle, X, is 217.1° which corresponds to the common anti nucleoside conformation. The deoxyribose ring, however, has the unusual C(1′)-exo conformation, with C(1′) displaced 0.608Å from the plane of C(2′), C(3′), C(4′) and O(4′). The conformation about the exocyclic C(4′)-C(5′) bond is gauche⁺.     

Crystal structure of methyl 3-amino-2,3-dideoxy-beta-D-arabino-hexopyranoside. Stabilization of the crystal lattice by a double network of N-H...O, O-H...N and O-H...O interactions

The structure, conformation and configuration of methyl 3-amino-2,3-dideoxy-beta-D-arabino-hexopyranoside were investigated by (1)H NMR, (13)C NMR and IR spectroscopy, as well as by optical rotation. The crystal structure was confirmed by single-crystal X-ray crystallographic analysis at 293 K and R = 0.0434 based on 910 independent reflections. The crystal belongs to the monoclinic system, space group of P2(1) with cell dimensions a = 6.050(1) Angstroms, b = 7.284(1) Angstroms, c = 10.289(2) Angstroms, beta = 104.69(3) degrees, D(c) = 1.341 Mg cm(-3) and V = 438.9(1) Angstroms(3) for Z = 2. Furthermore, the molecule has a typical (4)C(1) chair conformation. Hydrogen bonds between sugar molecules are responsible for stabilizing the crystal lattice.     

NMR conformational analysis of p-tolyl furanopyrimidine 2'-deoxyribonucleoside and crystal structure of its 3',5'-di-O-acetyl derivative

The conformation of a representative molecule of a new, potent class of antiviral-active modified nucleosides is determined. A bicyclic nucleoside, 3-(2'-deoxy-beta-D-ribofuranosyl)-6-(4-methylphenyl)-2,3-dihydrofuro[2,3-d]pyrimidin-2-one, shows C2'-endo and C3'-endo ribose conformations in solution (63:37, 37 degrees C; DMSO-d6), as determined by 1H NMR studies. The crystal structure of a 3',5'-di-O-acetyl-protected derivative (monoclinic, P21, a/b/c= 6.666(1)/12.225(1)/24.676(2) A, beta=90.24(1) degrees , Z=4) shows exclusively C2'-endo deoxyribose puckering. The base is found in the anti position both in solution and in crystalline form.     

Crystal structure of the alpha, beta, gamma-tridentate manganese complex of adenosine 5'-triphosphate cocrystallized with 2,2'-dipyridylamine

The 1:1:1 complex of Mn2+, ATP, and 2,2'-dipyridylamine (DPA) crystallizes as Mn-(HATP)2.Mn(H2O)6.(HDPA)2.12H2O in the orthorhombic space group C222(1) with unit cell dimensions a = 10.234 (3) A, b = 22.699 (3) A, and c = 31.351 (4) A. The structure was solved by the multisolution technique and refined by the least-squares method to a final R index of 0.072 using 3516 intensities. The structure is composed of two ATP molecules sharing a common manganese atom. The metal exhibits alpha, beta, gamma coordination to the triphosphate chains of two dyad-related ATP molecules, resulting in a hexacoordinated Mn2+ ion surrounded by six phosphate groups. The metal to oxygen distances are 2.205 (6), 2.156 (4), and 2.144 (5) A for the alpha-, beta-, and gamma-phosphate groups, respectively. No metal-base interactions are observed. There is a second hexaaqua-coordinated Mn2+ ion that is also located on a dyad axis. The hydrated manganese ions sandwich the phosphate-coordinated manganese ions in the crystal with a metal-metal distance of 5.322 A. The ATP molecule is protonated on the N(1) site of the adenine base and exhibits the anti conformation (chi = 66.0 degrees). The ribofuranose ring is in the 2/3 T conformation with pseudorotation parameters P = 179 (1) degrees and tau m = 34.1 (6) degrees. The adenine bases form hydrogen-bonded self-pairs across a crystallographic dyad axis and stack with both DPA molecules to form a column along the dyad. The structure of the metal-ATP complex provides information about the possible metal coordination, conformation, and environment of the nucleoside triphosphate substrate in the enzyme.     

Conformational investigation of alpha, beta-dehydropeptides. Part III. Molecular and crystal structure of acetyl-L-prolyl-alpha, beta-dehydrovaline methylamide.

The crystal structure of Ac-Pro-delta Val-NHCH3 was examined to determine the influence of the alpha,beta-dehydrovaline residue on the nature of peptide conformation. The peptide crystallizes from methanol-diethyl ether solution at 4 degrees in needle-shaped form in orthorhombic space group P2(1)2(1)2(1) with a = 11.384(2) A, b = 13.277(2) A, c = 9.942(1) A, V = 1502.7(4) A3, Z = 4, Dm = 1.17 g.cm-3 and Dc = 1.18 g.cm-3. The structure was solved by direct methods using SHELXS-86 and refined to an R value of 0.057 for 1922 observed reflections. The peptide is found to adopt a beta-bend between the type I and the type III conformation with phi 1 = -68.3(4) degrees, psi 1 = -20.1(4) degrees, phi 2 = -73.5(4) degrees and psi 2 = -14.1(4) degrees. An intramolecular hydrogen bond between the carbonyl oxygen of ith residue and the NH of (i + 3)th residue stabilizes the beta-bend. An additional intermolecular N...O hydrogen bond joins molecules into infinite chains. In the literature described crystal structures of peptides having a single alpha,beta-dehydroamino acid residue in the (i + 2) position and forming a beta-bend reveal a type II conformation.     

A comparative conformational study of thymidylyl(3'----5')-thymidine, thymidylyl(3'----5')-5'-thio-5'- deoxythymidine and thymidinylacetamido-[3'(O)----5'(C)]-5'-deoxythymidine

A comparative 270 MHz NMR spectroscopic study on the solution structure of the dimer d(TpT) 1, and its two analogues, namely, d(TpST) 2, and NH2d(TcmT) 4 has been reported. Analysis of chemical shifts and coupling constants indicate that: (i) The sugar moieties of the constituent nucleotides are not affected by modification of the internucleotide linkages and adopt preferentially an S-type conformation. (ii) The C4'-C5' bond in the pT part of the modified dimers 2 and 4 shows a large conformational freedom (gamma+ = 32% and 35%, respectively) compared to 1 (gamma+ = 75%). (iii) The population of the trans conformer about C5'-O5' is less important in d(TpST) 2 compared to d(TpT) 1. (iv) The C3'-O3' bond in 2 adopts a trans conformation as in 1. (v) The glycosidic bonds in the modified dimers 2 and 4 showed preferential syn conformation. UV and CD data show that the modified dimers 2 and 4 have poor tendency to stack intramolecularly, they also base pair less efficiently with d(ApA) as compared to d(TpT) 1.     

The crystal and molecular structure of 2'-deoxy-2'-fluoroinosine monohydrate.

The structure of the hydrate of 2'-deoxy-2'-fluoroinosine has been determined by single-crystal x-ray diffraction. The nucleoside crystallizes in space group P2(1)2(1)2(1) with unit cell dimensions, a = 33.291, b = 10. 871, c = 6.897A. There are two nucleosides and two water molecules in the asymmetric unit. The structure was solved by direct methods and refined to a residual R = 0.095. The two independent nucleosides in the asymmetric unit show different conformations about the glycosidic bond, while other structural details are similar. The base orientation to the sugar is syn in molecule A, whereas anti in molecule B. The exocyclic C(4')-C(5') bond conformation defined with respect to C(3')-C(4')-C(5')-O(5') is gauche+ in both molecules A and B. The sugar ring pucker defined by the pseudorotation phase angle P is a twisted conformation in both, C(3')-endo-C(4')-exo with P = 29 degrees in molecule A and C(4')-exo-C(3')-endo with P = 41 degrees in molecule B. It is shown by comparison with x-ray results of other 2'-fluoronucleosides and unmodified nucleosides including inosines that, in addition to a strong preference of the C(3')-endo type pucker, twisted conformations involving C(4')-exo puckering may be one of characteristic features of 2'-fluoronucleosides.