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1.
(Quasi‐)Racemic X‐ray Structures of Glycosylated and Non‐Glycosylated Forms of the Chemokine Ser‐CCL1 Prepared by Total Chemical Synthesis 下载免费PDF全文
Prof. Dr. Ryo Okamoto Dr. Kalyaneswar Mandal Dr. Michael R. Sawaya Prof. Dr. Yasuhiro Kajihara Prof. Dr. Todd O. Yeates Prof. Dr. Stephen B. H. Kent 《Angewandte Chemie (International ed. in English)》2014,53(20):5194-5198
Our goal was to obtain the X‐ray crystal structure of the glycosylated chemokine Ser‐CCL1. Glycoproteins can be hard to crystallize because of the heterogeneity of the oligosaccharide (glycan) moiety. We used glycosylated Ser‐CCL1 that had been prepared by total chemical synthesis as a homogeneous compound containing an N‐linked asialo biantennary nonasaccharide glycan moiety of defined covalent structure. Facile crystal formation occurred from a quasi‐racemic mixture consisting of glycosylated L ‐protein and non‐glycosylated‐D ‐protein, while no crystals were obtained from the glycosylated L ‐protein alone. The structure was solved at a resolution of 2.6–2.1 Å. However, the glycan moiety was disordered: only the N‐linked GlcNAc sugar was well‐defined in the electron density map. A racemic mixture of the protein enantiomers L ‐Ser‐CCL1 and D ‐Ser‐CCL1 was also crystallized, and the structure of the true racemate was solved at a resolution of 2.7–2.15 Å. Superimposition of the structures of the protein moieties of L ‐Ser‐CCL1 and glycosylated‐L ‐Ser‐CCL1 revealed there was no significant alteration of the protein structure by N‐glycosylation. 相似文献
2.
Plant Antimicrobial Peptides Snakin‐1 and Snakin‐2: Chemical Synthesis and Insights into the Disulfide Connectivity 下载免费PDF全文
Dr. Paul W. R. Harris Dr. Sung‐Hyun Yang Prof. Antonio Molina Gemma López Martin Middleditch Prof. Margaret A. Brimble 《Chemistry (Weinheim an der Bergstrasse, Germany)》2014,20(17):5102-5110
Antimicrobial peptides and proteins represent an important class of plant defensive compounds against pathogens and provide a rich source of lead compounds in the field of drug discovery. We describe the effective preparation of the cysteine‐rich snakin‐1 and ‐2 antimicrobial peptides by using a combination of solid‐phase synthesis and native chemical ligation. A subsequent cysteine/cystine mediated oxidative folding to form the six internal disulfide bonds concurrently gave the folded proteins in 40–50 % yield. By comparative evaluation of mass spectrometry, HPLC, biological data and trypsin digest mapping of folded synthetic snakin‐2 compared to natural snakin‐2, we demonstrated that synthetic snakin‐2 possesses full antifungal activity and displayed similar chromatographic behaviour to natural snakin‐2. Trypsin digest analysis allowed tentative assignment of three of the purported six disulfide bonds. 相似文献
3.
Benjamin J. Tombling Conan K. Wang David J. Craik 《Angewandte Chemie (International ed. in English)》2020,59(28):11218-11232
Disulfide bonds typically introduce conformational constraints into peptides and proteins, conferring improved biopharmaceutical properties and greater therapeutic potential. In our opinion, disulfide‐rich microdomains from proteins are potentially a rich and under‐explored source of drug leads. A survey of the UniProt protein database shows that these domains are widely distributed throughout the plant and animal kingdoms, with the EGF‐like domain being the most abundant of these domains. EGF‐like domains exhibit large diversity in their disulfide bond topologies and calcium binding modes, which we classify in detail here. We found that many EGF‐like domains are associated with disease phenotypes, and the interactions they mediate are potential therapeutic targets. Indeed, EGF‐based therapeutic leads have been identified, and we further propose that these domains can be optimized to expand their therapeutic potential using chemical design strategies. This Review highlights the potential of disulfide‐rich microdomains as future peptide therapeutics. 相似文献
4.
Radiation Damage and Racemic Protein Crystallography Reveal the Unique Structure of the GASA/Snakin Protein Superfamily 下载免费PDF全文
Ho Yeung Dr. Christopher J. Squire Yuliana Yosaatmadja Dr. Santosh Panjikar Gemma López Prof. Dr. Antonio Molina Prof. Dr. Edward N. Baker Dr. Paul W. R. Harris Prof. Dr. Margaret A. Brimble 《Angewandte Chemie (International ed. in English)》2016,55(28):7930-7933
Proteins from the GASA/snakin superfamily are common in plant proteomes and have diverse functions, including hormonal crosstalk, development, and defense. One 63‐residue member of this family, snakin‐1, an antimicrobial protein from potatoes, has previously been chemically synthesized in a fully active form. Herein the 1.5 Å structure of snakin‐1, determined by a novel combination of racemic protein crystallization and radiation‐damage‐induced phasing (RIP), is reported. Racemic crystals of snakin‐1 and quasi‐racemic crystals incorporating an unnatural 4‐iodophenylalanine residue were prepared from chemically synthesized d ‐ and l ‐proteins. Breakage of the C?I bonds in the quasi‐racemic crystals facilitated structure determination by RIP. The crystal structure reveals a unique protein fold with six disulfide crosslinks, presenting a distinct electrostatic surface that may target the protein to microbial cell surfaces. 相似文献
5.
Andrew M. White Simon J. de Veer Guojie Wu Peta J. Harvey Kuok Yap Gordon J. King Joakim E. Swedberg Conan K. Wang Ruby H. P. Law Thomas Durek David J. Craik 《Angewandte Chemie (International ed. in English)》2020,59(28):11273-11277
Ruthenium‐catalysed azide–alkyne cycloaddition (RuAAC) provides access to 1,5‐disubstituted 1,2,3‐triazole motifs in peptide engineering applications. However, investigation of this motif as a disulfide mimetic in cyclic peptides has been limited, and the structural consequences remain to be studied. We report synthetic strategies to install various triazole linkages into cyclic peptides through backbone cyclisation and RuAAC cross‐linking reactions. These linkages were evaluated in four serine protease inhibitors based on sunflower trypsin inhibitor‐1. NMR and X‐ray crystallography revealed exceptional consensus of bridging distance and backbone conformations (RMSD<0.5 Å) of the triazole linkages compared to the parent disulfide molecules. The triazole‐bridged peptides also displayed superior half‐lives in liver S9 stability assays compared to disulfide‐bridged peptides. This work establishes a foundation for the application of 1,5‐disubstituted 1,2,3‐triazoles as disulfide mimetics. 相似文献
6.
Katie Donnelly John F. Gallagher Alan J. Lough 《Acta Crystallographica. Section C, Structural Chemistry》2008,64(6):o335-o340
The three title isomers, 4‐, (I), 3‐, (II), and 2‐fluoro‐N′‐(4‐pyridyl)benzamide, (III), all C12H9FN2O, crystallize in the P21/c space group (No. 14) with similar unit‐cell parameters and are isomorphous and isostructural at the primary hydrogen‐bonding level. An intramolecular C—H...O=C interaction is present in all three isomers [C...O = 2.8681 (17)–2.884 (2) Å and C—H...O117–118°], with an additional N—H...F [N...F = 2.7544 (15) Å] interaction in (III). Intermolecular amide–pyridine N—H...N hydrogen bonds link molecules into one‐dimensional zigzag chains [graph set C(6)] along the [010] direction as the primary hydrogen bond [N...N = 3.022 (2), 3.049 (2) and 3.0213 (17) Å]. These are augmented in (I) by C—H...π(arene) and cyclic C—F...π(arene) contacts about inversion centres, in (II) by C—F...F—C interactions [C...F = 3.037 (2) Å] and weaker C—H...π(arene)/C—H...F contacts, and in (III) by C—H...π(arene) and C=O...O=C interactions, linking the alternating chains into two‐dimensional sheets. Typical amide N—H...O=C hydrogen bonds [as C(4) chains] are not present [N...O = 3.438 (2) Å in (I), 3.562 (2) Å in (II) and 3.7854 (16) Å in (III)]; the C=O group is effectively shielded and only participates in weaker interactions/contacts. This series is unusual as the three isomers are isomorphous (having similar unit‐cell parameters, packing and alignment), but they differ in their interactions and contacts at the secondary level. 相似文献
7.
New chiral [1]rotaxanes with aromatic bridges were prepared in yields up to 72% starting from a [2]rotaxane with sulfonamide groups in wheel and axle. The X‐ray structures of the parent [2]rotaxane 1 and of the three [1]rotaxanes 3e , g , h were solved which show networks of H‐bonds between wheel and axle. The separation of the racemic mixtures of four of the [1]rotaxanes, i.e., of 3a , b , d , e , was possible with HPLC on Chiralcel OD. The aromatic chromophores in the bridges lead to a considerable enhancement of the intensities of the molar CD as compared to the analogues with aliphatic bridges. In one case ( 3d ), the Cotton effects are as strong as those usually found in helicenes. 相似文献
8.
Zora Popovi Gordana Pavlovi Dubravka Matkovi‐alogovi
eljka Soldin 《Acta Crystallographica. Section C, Structural Chemistry》2003,59(5):m165-m167
The asymmetric unit of the title polymeric complex, [HgBr(C6H4NO2)]n or HgBr(nic), contains mercury coordinated via two Br atoms [Hg—Br = 2.6528 (9) and 2.6468 (9) Å], two carboxylate O atoms, which form a characteristic four‐membered chelate ring [Hg—O = 2.353 (6) and 2.478 (7) Å], and an N atom [Hg—N = 2.265 (5) Å], in the form of a very irregular (3+2)‐coordination polyhedron. The pronounced irregularity of the effective Hg (3+2)‐coordination is a result of the rigid stereochemistry of the nicotinate ligand. According to the covalent and van der Waals radii criteria, the strongest bonds are Hg—Br and Hg—N. These covalent interactions form a two‐dimensional polymer. The puckered planes are connected by van der Waals interactions, and there are only two intermolecular C—H⋯O hydrogen bonds [3.428 (10) and 3.170 (10) Å]. 相似文献
9.
George Ferguson Christopher Glidewell 《Acta Crystallographica. Section C, Structural Chemistry》2001,57(4):452-454
The title compound, N‐hydroxypropanamide, C3H7NO2, crystallizes with Z′ = 3 in P21/c. The molecules are linked by three N—H?O hydrogen bonds [N?O 2.8012 (16) to 2.8958 (15) Å; N—H?O 163 to 168°] and by three O—H?O hydrogen bonds [O?O 2.6589 (15) to 2.6775 (17) Å; O—H?O 165 to 177°] into a single three‐dimensional framework. 相似文献
10.
Afef Ghouili Ameni Brahmia Rached Ben Hassen 《Acta Crystallographica. Section C, Structural Chemistry》2015,71(10):873-877
A new polymorph (denoted polymorph II) of 3‐acetyl‐4‐hydroxy‐2H‐chromen‐2‐one, C11H8O4, was obtained unexpectedly during an attempt to recrystallize the compound from salt–melted ice, and the structure is compared with that of the original polymorph (denoted polymorph I) [Lyssenko & Antipin (2001). Russ. Chem. Bull. 50 , 418–431]. Strong intramolecular O—H...O hydrogen bonds are observed equally in the two polymorphs [O...O = 2.4263 (13) Å in polymorph II and 2.442 (1) Å in polymorph I], with a slight delocalization of the hydroxy H atom towards the ketonic O atom in polymorph II [H...O = 1.32 (2) Å in polymorph II and 1.45 (3) Å in polymorph I]. In both crystal structures, the packing of the molecules is dominated and stabilized by weak intermolecular C—H...O hydrogen bonds. Additional π–π stacking interactions between the keto–enol hydrogen‐bonded rings stabilize polymorph I [the centres are separated by 3.28 (1) Å], while polymorph II is stabilized by interactions between α‐pyrone rings, which are parallel to one another and separated by 3.670 (5) Å. 相似文献
11.
Konstantin V. Domasevitch 《Acta Crystallographica. Section C, Structural Chemistry》2008,64(6):o326-o329
In the title compound, 2C10H14N4·3C6HF5O, one of the pentafluorophenol molecules resides on a mirror plane bisecting the O...F axis. The components aggregate by N—H...N, N—H...O and O—H...N hydrogen bonds involving equal disordering of the H atoms into molecular ensembles based on a 2:1 pyrazole–phenol cyclic pattern [O...N = 2.7768 (16) Å and N...N = 2.859 (2) Å], crosslinked into one‐dimensional columns via hydrogen bonding between the outer pyrazole groups and additional pentafluorophenol molecules. The latter yields a 1:1 pyrazole–phenol catemer with alternating strong O—H...N [2.5975 (16) Å] and weaker N—H...O [2.8719 (17) Å] hydrogen bonds. This is the first reported molecular adduct of a pentafluorinated phenol and a nitrogen base, and suggests the utility of highly acidic phenols and pyrazoles for developing hydrogen‐bonded cocrystals. 相似文献
12.
Alan K. Brisdon Abeer M. T. Muneer Robin G. Pritchard 《Acta Crystallographica. Section C, Structural Chemistry》2015,71(10):900-902
Halogen bonding is an intermolecular interaction capable of being used to direct extended structures. Typical halogen‐bonding systems involve a noncovalent interaction between a Lewis base, such as an amine, as an acceptor and a halogen atom of a halofluorocarbon as a donor. Vapour‐phase diffusion of 1,4‐diazabicyclo[2.2.2]octane (DABCO) with 1,2‐dibromotetrafluoroethane results in crystals of the 1:1 adduct, C2Br2F4·C6H12N2, which crystallizes as an infinite one‐dimensional polymeric structure linked by intermolecular N...Br halogen bonds [2.829 (3) Å], which are 0.57 Å shorter than the sum of the van der Waals radii. 相似文献
13.
Diaminodiacid Bridges to Improve Folding and Tune the Bioactivity of Disulfide‐Rich Peptides 下载免费PDF全文
Ye Guo De‐Meng Sun Feng‐Liang Wang Yao He Prof. Lei Liu Prof. Chang‐Lin Tian 《Angewandte Chemie (International ed. in English)》2015,54(48):14276-14281
Disulfide‐rich peptides containing three or more disulfide bonds are promising therapeutic and diagnostic agents, but their preparation is often limited by the tedious and low‐yielding folding process. We found that a single cystine‐to‐diaminodiacid replacement could significantly increase the folding efficiency of disulfide‐rich peptides and thus improve their production yields. The practicality of this strategy was demonstrated by the synthesis and folding of derivatives of the μ‐conotoxin SIIIA, the preclinical hormone hepcidin, and the trypsin inhibitor EETI‐II. NMR and X‐ray crystallography studies confirmed that these derivatives of disulfide‐rich peptide retained the correct three‐dimensional conformations. Moreover, the cystine‐to‐diaminodiacid replacement enabled structural tuning, thereby leading to an EETI‐II derivative with higher bioactivity than the native peptide. 相似文献
14.
John N. Low Antonio Quesada Antonio Marchal Manuel Melguizo Manuel Nogueras Christopher Glidewell 《Acta Crystallographica. Section C, Structural Chemistry》2002,58(5):o289-o294
Molecules of 2‐amino‐4,6‐dimethoxypyrimidine, C6H9N3O2, (I), are linked by two N—H?N hydrogen bonds [H?N 2.23 and 2.50 Å, N?N 3.106 (2) and 3.261 (2) Å, and N—H?N 171 and 145°] into a chain of fused rings, where alternate rings are generated by centres of inversion and twofold rotation axes. Adjacent chains are linked by aromatic π–π‐stacking interactions to form a three‐dimensional framework. In 2‐benzylamino‐4,6‐bis(benzyloxy)pyrimidine, C25H23N3O2, (II), the molecules are linked into centrosymmetric R(8) dimers by paired N—H?N hydrogen bonds [H?N 2.13 Å, N?N 2.997 (2) Å and N—H?N 170°]. Molecules of 2‐amino‐4,6‐bis(N‐pyrrolidino)pyrimidine, C12H19N5, (III), are linked by two N—H?N hydrogen bonds [H?N 2.34 and 2.38 Å, N?N 3.186 (2) and 3.254 (2) Å, and N—H?N 163 and 170°] into a chain of fused rings similar to that in (I). 相似文献
15.
Ryota Inoue Masashi Hasegawa Tohru Nishinaga Kenji Yoza Yasuhiro Mazaki 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2015,127(9):2772-2776
A series of thiacalix[n]dithiothiophenes (n=4–10) was prepared by a facile method and X‐ray analysis was used to determine the molecular structures of square‐ (4‐mer) and pentagonal‐shaped macrocycles (5‐mer). In the cyclic voltammograms, reversible multielectron redox processes, which are due to electronic delocalization, were observed at low oxidation potentials. The cyclic 4‐mer acted as a “Janus‐head” cavitand for two C60 molecules, whereas the 5‐ and 6‐mer formed stable 1:1 complexes with C60 . 相似文献
16.
Efficient Synthesis,Structure, and Complexation Studies of Electron‐Donating Thiacalix[n]dithienothiophene 下载免费PDF全文
Ryota Inoue Dr. Masashi Hasegawa Prof. Tohru Nishinaga Dr. Kenji Yoza Prof. Yasuhiro Mazaki 《Angewandte Chemie (International ed. in English)》2015,54(9):2734-2738
A series of thiacalix[n]dithiothiophenes (n=4–10) was prepared by a facile method and X‐ray analysis was used to determine the molecular structures of square‐ (4‐mer) and pentagonal‐shaped macrocycles (5‐mer). In the cyclic voltammograms, reversible multielectron redox processes, which are due to electronic delocalization, were observed at low oxidation potentials. The cyclic 4‐mer acted as a “Janus‐head” cavitand for two C60 molecules, whereas the 5‐ and 6‐mer formed stable 1:1 complexes with C60 . 相似文献
17.
Gordana Pavlovi Zora Popovi
eljka Soldin Dubravka Matkovi‐alogovi 《Acta Crystallographica. Section C, Structural Chemistry》2000,56(7):801-803
The reaction of 1‐methyl‐1,3‐imidazole‐2‐thione (meimtH) with mercury(II) iodide in methanol in a 2:1 molar ratio resulted in the formation of single crystals of the title compound, [HgI2(C4H6N2S)2]. The Hg atom is coordinated by two I [2.7809 (9) and 2.7999 (8) Å] and two thione S atoms [2.520 (3) and 2.576 (3) Å] with irregular tetrahedral coordination geometry. The NH groups of the imidazole ring take part in intra‐ and intermolecular hydrogen bonds with I atoms [N?I 3.596 (8) and 3.611 (9) Å, respectively] joining molecules into infinite chains parallel to the z axis. 相似文献
18.
Yue Pan Kunhao Li Wenhua Bi Jing Li 《Acta Crystallographica. Section C, Structural Chemistry》2008,64(2):o41-o43
The cocrystallization of adamantane‐1,3‐dicarboxylic acid (adc) and 4,4′‐bipyridine (4,4′‐bpy) yields a unique 1:1 cocrystal, C12H16O4·C10H8N2, in the C2/c space group, with half of each molecule in the asymmetric unit. The mid‐point of the central C—C bond of the 4,4′‐bpy molecule rests on a center of inversion, while the adc molecule straddles a twofold rotation axis that passes through two of the adamantyl C atoms. The constituents of this cocrystal are joined by hydrogen bonds, the stronger of which are O—H...N hydrogen bonds [O...N = 2.6801 (17) Å] and the weaker of which are C—H...O hydrogen bonds [C...O = 3.367 (2) Å]. Alternate adc and 4,4′‐bpy molecules engage in these hydrogen bonds to form zigzag chains. In turn, these chains are linked through π–π interactions along the c axis to generate two‐dimensional layers. These layers are neatly packed into a stable crystalline three‐dimensional form via weak C—H...O hydrogen bonds [C...O = 3.2744 (19) Å] and van der Waals attractions. 相似文献
19.
Dubravka Matkovi‐alogovi Jasminka Popovi Zora Popovi Igor Picek
eljka Soldin 《Acta Crystallographica. Section C, Structural Chemistry》2002,58(1):m39-m40
The title compound, [HgBr(C7H4NO4)(H2O)], was obtained by the reaction of an aqueous solution of mercury(II) bromide and pyridine‐2,6‐dicarboxylic acid (picolinic acid, dipicH2). The shortest bond distances to Hg are Hg—Br 2.412 (1) Å and Hg—N 2.208 (5) Å; the corresponding N—Hg—Br angle of 169.6 (1)° corresponds to a slightly distorted linear coordination. There are also four longer Hg—O interactions, three from dipicH? [2.425 (4) and 2.599 (4) Å within the asymmetric unit, and 2.837 (4) Å from a symmetry‐related molecule] and one from the bonded water molecule [2.634 (4) Å]. The effective coordination of Hg can thus be described as 2+4. The molecules are connected to form double‐layer chains parallel to the y axis by strong O—H?O hydrogen bonds between carboxylic acid groups of neighbouring molecules, and by weaker hydrogen bonds involving both H atoms of the water molecule and the O atoms of the carboxylic acid groups. 相似文献
20.
In order to search for novel antitumor and antiviral agents with high activity and low toxicity, some 2‐propyl‐5‐(substituted)phenyl‐1,4‐dioxo‐1,2,3,4,5,6,7,8‐octahydro‐[1,4,2]diazaphosphorino[1,2‐a][1,3,2]benzodiazaphosphorine 3‐oxides ( 2a–e ) have been designed incorporating the proximate carbonyl and phosphoryl groups into the benzoannulated phosphadiamide heterocycle and synthesized in acceptable yields. These compounds contain the proximate carbonyl and phosphoryl groups in the fused heterocycle. Their structures were confirmed by spectroscopic methods and microanalyses. The results from X‐ray crystallography analysis of 2a showed that the proximate carbonyl and phosphoryl groups are not coplanar because of their being jointly located in the fused heterocycle, having ring tension, and this then destroys the conjugation between the CO and the PO moieties. As a result, the length of the P C bonds measured as 1.851(3)–1.852(3) Å are just the same as that of a P C bond not involved in conjugation (1.80–1.85 Å). Also,the C(1), C(2), C(3), N(2), N(3), and P(1) atoms of the [1,4,2]diazaphosphorino moiety exist preferably in the boat conformation. The coplanar C(1), C(3), N(2), and N(3) atoms, within an average deviation of 0.0102 Å, form the ground floor of the boat conformation, whereas the P(1) and C(2) atoms are on the same side of the coplanar structure with the distance of 0.7067 and 0.6315 Å, respectively. © 2002 John Wiley & Sons, Inc. Heteroatom Chem 13:63–71, 2002; DOI 10.1002/hc.1107 相似文献