Half Of Molecules Research Articles

General strategies for IgG-like bispecific antibody purification.

Bispecific antibodies (bsAbs) can simultaneously bind two different antigens or epitopes. Their dual-targeting capability enables novel mechanisms of action, gaining therapeutic advantages over conventional monospecific mAbs. In recent years, the number of bsAbs grows rapidly and bsAbs under development are available in diverse formats. In particular, Fc-containing IgG-like bsAbs, which represent the major group, can be constructed in asymmetric or symmetric format. For asymmetric ones, whose assembly requires multiple distinct chains, although numerous strategies have been developed to promote desired chain pairing, product-related variants such as free chains, half molecules and mispaired species are usually present at various levels. For symmetric ones, increased level of aggregates and truncating variants is often associated with their production. In general, bsAbs pose greater challenges to the downstream team than regular mAbs. In the past few years, our team successfully developed the downstream process for over 70 bsAbs in greater than 30 different formats and accumulated substantial experience. This review introduces general strategies that we have used while purifying these challenging molecules.

The tRNAVal half: A strong endogenous Toll-like receptor 7 ligand with a 5′-terminal universal sequence signature

Toll-like receptors (TLRs) are crucial components of the innate immune system. Endosomal TLR7 recognizes single-stranded RNAs, yet its endogenous ssRNA ligands are not fully understood. We previously showed that extracellular (ex-) 5'-half molecules of tRNAHisGUG (the 5'-tRNAHisGUG half) in extracellular vesicles (EVs) of human macrophages activate TLR7 when delivered into endosomes of recipient macrophages. Here, we fully explored immunostimulatory ex-5'-tRNA half molecules and identified the 5'-tRNAValCAC/AAC half, the most abundant tRNA-derived RNA in macrophage EVs, as another 5'-tRNA half molecule with strong TLR7 activation capacity. Levels of the ex-5'-tRNAValCAC/AAC half were highly up-regulated in macrophage EVs upon exposure to lipopolysaccharide and in the plasma of patients infected with Mycobacterium tuberculosis. The 5'-tRNAValCAC/AAC half-mediated activation of TLR7 effectively eradicated bacteria infected in macrophages. Mutation analyses of the 5'-tRNAValCAC/AAC half identified the terminal GUUU sequence as a determinant for TLR7 activation. We confirmed that GUUU is the optimal ratio of guanosine and uridine for TLR7 activation; microRNAs or other RNAs with the terminal GUUU motif can indeed stimulate TLR7, establishing the motif as a universal signature for TLR7 activation. These results advance our understanding of endogenous ssRNA ligands of TLR7 and offer insights into diverse TLR7-involved pathologies and their therapeutic strategies.

Synthesis, Crystal Structure, Computational Investigation of Vanillin Azine Derivative as Potent Blocker of the N‐Terminal Ras‐Binding Domain (RBD) in Human a‐Raf Kinase

AbstractVanillin is the main component of natural vanilla extract and is responsible for its flavoring properties. Besides its well‐known applications as an additive in food and cosmetics. In this, we have synthesized a new vanillin derivative. Its structure was characterized by IR, MS, NMR and confirmed by single‐crystal X‐ray analysis. The asymmetric unit of the title molecule consists of two independent half molecules, each having crystallographically imposed centrosymmetry. Reticular layers approximately parallel to the bc plane are generated from one molecule through O−H⋅⋅⋅N hydrogen bonds. The layers are linked by the second molecule through O−H⋅⋅⋅O hydrogen bonds to form a 3‐D network structure. We carried out density functional investigations to understand the compound‘s molecular reactivity and chemical stability. Frontier molecular orbital (FMO) analysis, global reactivity, and Fukui parameters were calculated at the B3LYP/6‐31+G(d,p) method. In 20 % to 30 % of human malignancies, RAS genes are activated ontogenetically by point mutations. New strategies to block this oncogenic protein are needed since it has proven difficult to create efficient RAS inhibitors. The above‐titled compound shows better structural activity relationship studies against Ras‐binding domine, based on this molecular docking simulation as well as the drug‐likeness analysis carried out for our newly synthesized compound.

Crystal structure and Hirshfeld surface analysis of 8-benzyl-1-[(4-methyl-phen-yl)sulfon-yl]-2,7,8,9-tetra-hydro-1H-3,6:10,13-diep-oxy-1,8-benzodi-aza-cyclo-penta-decine ethanol hemisolvate.

The asymmetric unit of the title compound, 2C31H28N2O4S·C2H6O, contains a parent mol-ecule and a half mol-ecule of ethanol solvent. The main compound stabilizes its mol-ecular conformation by forming a ring with an R 1 2(7) motif with the ethanol solvent mol-ecule. In the crystal, mol-ecules are connected by C-H⋯O and O-H⋯O hydrogen bonds, forming a three-dimensional network. In addition, C-H⋯π inter-actions also strengthen the mol-ecular packing.

A new paddle wheel type Cu(II) complex with photoluminescence and photocatalytic properties

A paddle wheel-shaped complex formulated [Cu2(piv)4(CH3OH)2]·1.5(CH3OH)·0.5(H2O) (1) has been synthesized by a reaction of Cu(NO3)2·3H2O with pivalic acid. The structure of the complex is characterized by FTIR, elemental analysis and single X-ray crystallography. The crystal structure demonstrates that complex exhibits a paddle wheel type configuration. The asymmetric unit of 1 is composed of a half molecule due to the existence of an inversion center between the two Cu(II) centers. The oxygen atoms of the pivalate serve as bridging ligands, and the two methanol molecules occupy the axial position. Each pivalate ion has syn-, syn- coordination mode and its geometry may be described as square pyramidal. The complex works well as a photocatalyst, breaking down methylene blue (MB) by 78.26% after 120 minutes of 30 W ultraviolet light exposure. The optimized photocatalytic parameters were as follows; catalyst loading = 40 mg, primary concentration of MB = 15 mg/L, temperature = 323K, and pH = 8. The reaction kinetics were best demonstrated by a pseudo-first-order kinetic model followed by a rate constant of 0.00715 min–1. The reuse of the catalyst over five photocatalytic runs suggested its excellent sustainability and recyclability. Hydroxyl radicals and superoxide anions were found to be active participants in the catalytic reaction, as investigated by scavenging studies. These findings contributed to a deeper understanding of the mechanistic aspects of the photocatalytic reaction. Theoretical investigation is well support to experimental work.

Synthesis and crystal structure of a cadmium(II) coordination polymer based on 4,4′-(1H-1,2,4-triazole-3,5-diyl)dibenzoate

The asymmetric unit of the title compound, catena-poly[[[aquabis(pyridine-κN)cadmium(II)]-μ2-4,4′-(1H-1,2,4-triazole-3,5-diyl)dibenzoato-κ4 O,O′:O′′,O′′′] 4.5-hydrate], {[Cd(C16H9N3O4)(C5H5N)2(H2O)]·4.5H2O} n or {[Cd(bct)(py)2(H2O)]·4.5H2O} n (I), consists of a Cd2+ cation coordinated to one bct2– carboxylate dianion, two molecules of pyridine and a water molecule as well as four and a half water molecules of crystallization. The metal ion in I possesses a pentagonal–bipyramidal environment with the four O atoms of the two bidentately coordinated carboxylate groups and the N atom of a pyridine molecule forming the O4N equatorial plane, while the N atom of another pyridine ligand and the O atom of the water molecule occupy the axial positions. The bct2– bridging ligand connects two metal ions via its carboxylic groups, resulting in the formation of a parallel linear polymeric chain running along the [1\overline{1}1] direction. The coordinated water molecule of one chain forms a strong O—H...O hydrogen bond with the carboxylate O atom of a neighboring chain, leading to the formation of double chains with a closest distance of 5.425 (7) Å between the cadmium ions belonging to different chains. Aromatic π–π stacking interactions between the benzene fragments of the anions as well as between the coordinated pyridine molecules belonging to different chains results in the formation of sheets oriented parallel to the (\overline{1}01) plane. As a result of hydrogen-bonding interactions involving the water molecules of crystallization, the sheets are joined together in a three-dimensional network.

Expression of Multispecific Antibodies.

Bi- and multispecific antibody formats allow the development of new therapeutic strategies to address previously unmet medical needs. However, due to the increased complexity (e.g., the interface design and the presence of multiple binders), such molecules are generally more challenging to express and purify compared to standard monoclonal antibodies (mAbs). We describe here an optimized methodology to express and purify basic bispecific antibodies using the BEAT® interface. This interface allows to generate antibodies with very high levels of heterodimer product (reported titers exceed 10g/L) and comes with a built-in purification strategy allowing removal of residual levels of undesired product-related impurities (e.g., homodimers and half molecules).

Synthesis, single crystal X-ray structure determination, Hirshfeld surface analysis, interaction energies, and density functional theory calculations of N,N'-(cyclohexane-1,4-dicarbonothioyl)bis(4-methylbenzamide)

The present research offers convenient synthesis, molecular and crystal structures of C2 symmetric N,N'-(cyclohexane-1,4-dicarbonothioyl)bis(4-methylbenzamide). The synthesized bis-amide crystallized in monoclinic crystal system, having space group of P 21/c with a = 17.8669 (14) Å, b = 6.3495 (5) Å, c = 9.6195 (7) Å, β = 101.567 (8)°, Z = 2 and V = 1069.13 (15) Å3. The asymmetric unit contains cyclohexane ring located on an inversion center, one dicarbonothioyl and one methylbenzamide group. In the crystal structure, the N–H···O, C–H···O and C–H···S hydrogen bonds link the molecules, enclosing R21(6), R22(16) and R22(22) ring motifs, into three-dimensional architecture. Hirshfeld surface (HS) analysis revealed the prevailing significance of hydrogen bond contacts. HS analysis suggested prominent contributions for crystal packing encompasses H…H (49.6%), H…C/C…H (18.9%) and H…S/S…H (16.0%). Hydrogen bonding and van der Waals contacts are the dominant interactions in the crystal packing. The respective volume of the crystal voids and the percentage of free spaces in the unit cell is calculated as 117.87 Å3 and 11.02% indicating the absence of any large cavity within the crystal and the associated stability of the crystal. Evaluation of the electrostatic, dispersion and total energy frameworks revealed that stabilization is dominated by dispersion energy contribution. Moreover, optimized molecular structure, using density functional theory at B3LYP/6-311G(d,p) level, were compared with the experimentally determined ones. HOMO–LUMO energy gap was determined, frequencies and molecular electrostatic potential surface were calculated at the B3LYP/6–311G level to predict sites for electrophilic and nucleophilic attacks. The significant charge polarity, half molecule spread of HOMO and LUMO impart bis-amide nucleophilic as well as electrophilic behavior with relative potency depending upon the nature of the attacking molecule.

Synthesis, Molecular and Supramolecular Structure Aspects, and Antimicrobial Activity of the Centrosymmetric [Ag(5-Nitroquinoline)2]ClO4 Complex

The new homoleptic [Ag(5-nitroquinoline)2]ClO4 centrosymmetric complex was synthesized and its structure aspects were investigated. It crystallized in the monoclinic space group C2/c with a = 10.0279(2) Å, b = 13.2295(3) Å, c = 14.7552(3) Å and β = 102.1050(10)° while V = 1913.96(7) Å3 and half molecule as asymmetric formula. The Ag(I) is coordinated with two symmetrically related 5-nitroquinoline ligand units via the heterocyclic nitrogen atom with Ag-N distance of 2.146(6) Å and N1-Ag-N1 angle of 173.0(3)°. The two coordinated 5-nitroquinoline have anti configuration to one another and the perchlorate anion is set freely uncoordinated. The only Ag…O interactions are Ag1…O2 (3.110 Å) and Ag1…O1 (3.189 Å) which occur between the Ag(I) in one complex unit and the O-atoms from the NO2 groups in the neighbouring complex units. Hence, Ag(I) has coordination number 2 and its coordination geometry is slightly bent. Hirshfeld analysis indicated that the O…H (51.1%), C…H (11.8%), H…H (10.8%) and C…C (8.9%) contacts are the most common. Exclusively, the O…H, C…O, N…O, O…O and Ag…O contacts are the only shorter contacts than the vdWs radii sum of the interacting atoms. The studied Ag(I) complex showed good antimicrobial activity. It has comparable antibacterial activity against P. vulgaris (MIC = 9.7 μg/mL) and S. aureus (39.1 μg/mL) to Gentamycin (4.8 and 9.7 μg/mL, respectively) while better antifungal activity against A. fumigatus (MIC = 39.1 μg/mL) than Ketoconazole (156.2 μg/mL).

Mechanistic modeling of a human IgG4 monoclonal antibody (tralokinumab) Fab-arm exchange with endogenous IgG4 in healthy volunteers.

Therapeutic IgG4 antibodies engage in Fab‐arm exchange with endogenous human immunoglobulin G4 (IgG4) to form monovalent hybrid molecules. A mechanistic population model was developed to quantitatively characterize the dynamic Fab‐arm exchange of tralokinumab, a human IgG4 monoclonal antibody currently being developed for the treatment of atopic dermatitis, with endogenous IgG4 in healthy volunteers. The estimated pharmacokinetic parameters for IgG4 were similar to those of immunoglobulin G1 or immunoglobulin G2 in humans. However, the mechanistically modeled clearance of half molecules is 21‐fold higher, likely due to the loss of avidity for the neonatal Fc receptor. Half molecules of tralokinumab randomly associate with those of endogenous IgG4 to form monovalent hybrid molecules, which became the dominant form of tralokinumab within 1 day postdose in healthy volunteers. As the potency of monovalent tralokinumab is comparable with that of bivalent tralokinumab, the IgG4 Fab‐arm exchange with endogenous IgG4 is not expected to affect the potency of neutralization of interleukin‐13 in vivo.

Systematic analysis and comparison of ABC proteins superfamily confer structural, functional and evolutionary insights into four cotton species

ATP binding cassette transporters (ABCTs) is one of the largest gene superfamily comprising of integral membrane proteins that are ubiquitously found in all domains of life and implicated in ATP dependent active transport of ligands across the concentration gradient. We present here the identification and distribution of ABC proteins from seven plant species into four groups (Full, Half, Quarter and ABC2 molecules), eight families (ABCA to ABCG and ABCI) and twelve sub families (MDR, PDR, MRP, PMP, AOH, ATH, ATM, TAP, WBC, RLI, GCN and NAP) based on topology, orientation, size, and phylogenetic relationships with main focus on four cotton species especially tetraploid Gossypium hirsutum (Gh) encoding 320 ORFs. Dynamics of complex formation of structurally characterized ABCTs from each subfamily shows their kinetic and molecular mechanisms to combine the ATP hydrolysis and binding for substrate translocation, portraying a "structure to function relationship". Analysis of protein motif and genomic organizations displayed structural and functional conservation within same subfamily but diverged among the different subfamilies. Abundance of small sized single ABCs signifies the higher gene death/birth rate and ongoing evolution for functional advancements and environmental adaptability. Gene duplication relationship analysis illustrates the major role of tandem and segmental duplication in large scale expansion of ABC gene family in mentioned species. The overall Ka/Ks ratio indicated the intense purifying selection of ABC genes in four cotton species during evolution. In addition, tissue specific expression profiling, abiotic stress resistance and Co-expression networking of GhABCs infers their role in diverse range of molecular, cellular and biological processes. Cis-elements and gene enrichments also supported their predicted roles in substrates translocation, xenobiotic detoxification, lipid metabolism, hormonal and abiotic stresses responses. Forward and reverse genetics along with evolutionary trajectories, structural dynamics and validated expression profiling will provide much-needed clarity and a qualitative molecular framework for future research. This study will further broaden our insights into the evolution and functional elucidation of ABC gene family in cotton.

(μ-2,2',2'',2'''-{[Pyrazine-2,3,5,6-tetra-yltetra-kis(methyl-ene)]tetra-kis(sulfanedi-yl)}tetra-acetato)bis-[aqua-nickel(II)] hepta-hydrate.

Reaction of the ligand 2,2',2'',2'''-{[pyrazine-2,3,5,6-tetra-yltetra-kis-(methyl-ene)]tetra-kis-(sulfanedi-yl)}tetra-acetic acid (H4L1), with NiCl2 leads to the formation of a binuclear complex, (μ-2,2',2'',2'''-{[pyrazine-2,3,5,6-tetra-yltetra-kis-(methyl-ene)]tetra-kis-(sulfanedi-yl)}tetra-acetato-κ5 O,S,N 1,S',O':κ5 O'',S'',N 4,S''',O''')bis[aqua-nickel(II)] hepta-hydrate, {[Ni2(C16H16N2O8S4)(H2O)2]·7H2O} (I). It crystallizes with two half mol-ecules in the asymmetric unit. The complete mol-ecules are generated by inversion symmetry, with the center of the pyrazine rings being located at crystallographic centres of inversion. The ligand coordinates two NiII ions in a bis-penta-dentate manner and the sixfold coordination sphere of each nickel(II) atom (NiS2O3N) is completed by a water mol-ecule. The complex crystallized as a hepta-hydrate. The binuclear complexes are linked by Owater-H⋯Ocarbon-yl hydrogen bonds, forming layers parallel to the (101) plane. This layered structure is additionally stabilized by weak C-H⋯O hydrogen bonds. Further O-H⋯O hydrogen bonds involving binuclear complexes and solvent water mol-ecules, together with weak C-H⋯S hydrogen bonds, link the layers to form a supra-molecular framework.

Exploring crystal structure of 5, 10, 15, 20-tetrakis (4-iodophenyl) porphyrin; H2TIPP: Experimental and theoretical investigations

The present work represents chemical preparation, characterization, and crystal structure analysis combined with computational density functional theory; DFT and hirshfeld surface analysis; HSA of 5, 10, 15, 20-tetrakis (4-iodophenyl) porphyrin; H2TIPP. The title compound crystallizes in triclinic crystal system in space group P-1 having half molecule in asymmetric unit cell. Molecular packing seems to be controlled by various molecular interactions and has been put in evident and further addressed by HSA. The geometry obtained displays that the porphyrin core including the pyrrole rings and meso-carbon junction opts a planar geometry. However the phenyl rings containing iodine substituents are twisted from that core plane approximately perpendicular to each other and can be visualized as a slightly distorted propeller. Examining experimental and theoretical geometry confirms strong N_H∙∙∙N intramolecular hydrogen bonding involving in formation of qausi aromatic six membered rings at opposite ends inside the core, other prominent neighboring interaction exhibits interplay of N-H, H-H, C-H, C-I, and I∙∙∙I. Furthermore its quite evident those functional substituents at peripheral groups are quite flexible and directional, which has improved their orientation from one dimensional to 2D and 3D supramolecular architecture. This reflects their greater role as porous solids.

In vitro production and multiplex quantification of 2',3'-cyclic phosphate-containing 5'-tRNA half molecules.

RNA cleavages by many ribonucleases generate RNA molecules that contain a 2',3'-cyclic phosphate (cP) at their 3'-termini, and many cP-containing RNAs (cP-RNAs) are expressed as functional molecules in cells and tissues. 5'-tRNA half molecules are representative examples of functional cP-RNAs, playing important roles in various biological processes. We here show in vitro production of cP-containing 5'-tRNA half molecules that is able to prepare abundant synthetic cP-RNAs enough for functional analyses. Furthermore, we report a multiplex TaqMan RT-qPCR method which can simultaneously quantify multiple cP-containing 5'-tRNA half species. The method enabled us to efficiently quantify 5'-tRNA halves using samples with limited amounts, such as human plasma samples, revealing drastic enhancement of 5'-tRNA half levels at approximately 1,000-fold in patients infected with Mycobacterium tuberculosis. These in vitro production and multiplex quantification methods can be applied to any cP-RNAs, and they provide cost-effective, in-house techniques to accelerate expressional and functional characterizations of 5'-tRNA halves and other cP-RNAs.

Infection-induced 5'-half molecules of tRNAHisGUG activate Toll-like receptor 7.

Toll-like receptors (TLRs) play a crucial role in the innate immune response. Although endosomal TLR7 recognizes single-stranded RNAs, their endogenous RNA ligands have not been fully explored. Here, we report 5′-tRNA half molecules as abundant activators of TLR7. Mycobacterial infection and accompanying surface TLR activation up-regulate the expression of 5′-tRNA half molecules in human monocyte-derived macrophages (HMDMs). The abundant accumulation of 5′-tRNA halves also occur in HMDM-secreted extracellular vehicles (EVs); the abundance of EV-5′-tRNAHisGUG half molecules is >200-fold higher than that of the most abundant EV-microRNA (miRNA). Sequence identification of the 5′-tRNA halves using cP-RNA-seq revealed abundant and selective packaging of specific 5′-tRNA half species into EVs. The EV-5′-tRNAHisGUG half was experimentally demonstrated to be delivered into endosomes in recipient cells and to activate endosomal TLR7. Up-regulation of the 5′-tRNA half molecules was also observed in the plasma of patients infected with Mycobacterium tuberculosis. These results unveil a novel tRNA-engaged pathway in the innate immune response and assign the role of “immune activators” to 5′-tRNA half molecules.

Characterization of Bispecific Antibody Production in Cell Cultures by Unique Mixed Mode Size Exclusion Chromatography.

Bispecific antibodies have received wide attention as promising immunotherapeutic agents because of their high specificity and the ability to target immune cells to tumors. However, analysis of bispecific antibodies is challenging because multiple forms of antibodies are potentially generated during production in cell culture. Most analyses of bispecific antibodies rely on liquid chromatography with mass spectrometry (LC-MS), which could miss detection or becomes less quantitative if those forms are not physically separated. Here, we report a novel and sensitive mixed mode size exclusion chromatography (MM SEC) coupled with multiangle light scattering (MALS) to analyze different forms of bispecific IgG molecules under native conditions. The method displayed great ability to separate various antibody forms with peak resolutions unmatched by other methods we tested, isolating desired bispecific molecules, parental homodimers, half molecules, and antibodies with mispaired light and heavy chains. Each peak was analyzed by online MALS and then identified and confirmed by intact and reduced LC-MS of isolated forms. MM SEC in this study performs by a novel mechanism through the interactions of resin with protein surface hydrophobic clusters distributed across CDRs of light chains. This novel MM SEC allows quantitative detection of even low abundance forms and provides a new tool for screening expression profiles of cell culture clones, monitoring purification, and evaluating drug substance purity.

Synthesis, crystal structure and Hirshfeld and thermal analysis of bis[benzyl 2-(heptan-4-yl-idene)hydrazine-1-carboxyl-ate-κ2 N 2,O]bis(thio-cyanato)-nickel(II).

The title centrosymmetric NiII complex, [Ni(NCS)2(C15H22N2O2)2], crystallizes with one half mol-ecule in the asymmetric unit of the monoclinic unit cell. The complex adopts an octa-hedral coordination geometry with two mutually trans benzyl-2-(heptan-4-yl-idene)hydrazine-1-carboxyl-ate ligands in the equatorial plane with the axial positions occupied by N-bound thio-cyanato ligands. The overall conformation of the mol-ecule is also affected by two, inversion-related, intra-molecular C-H⋯O hydrogen bonds. The crystal structure features N-H⋯S, C-H⋯S and C-H⋯N hydrogen bonds together with C-H⋯π contacts that stack the complexes along the b-axis direction. The packing was further explored by Hirshfeld surface analysis. The thermal properties of the complex were also investigated by simultaneous TGA-DTA analyses.

Direct interaction of metastasis-inducing S100P protein with tubulin causes enhanced cell migration without changes in cell adhesion.

Overexpression of S100P promotes breast cancer metastasis in animals and elevated levels in primary breast cancers are associated with poor patient outcomes. S100P can differentially interact with nonmuscle myosin (NM) isoforms (IIA > IIC > IIB) leading to the redistribution of actomyosin filaments to enhance cell migration. Using COS-7 cells which do not naturally express NMIIA, S100P is now shown to interact directly with α,β-tubulin in vitro and in vivo with an equilibrium Kd of 2–3 × 10−7 M. The overexpressed S100P is located mainly in nuclei and microtubule organising centres (MTOC) and it significantly reduces their number, slows down tubulin polymerisation and enhances cell migration in S100P-induced COS-7 or HeLa cells. It fails, however, to significantly reduce cell adhesion, in contrast with NMIIA-containing S100P-inducible HeLa cells. When taxol is used to stabilise MTs or colchicine to dissociate MTs, S100P's stimulation of migration is abolished. Affinity-chromatography of tryptic digests of α and β-tubulin on S100P-bound beads identifies multiple S100P-binding sites consistent with S100P binding to all four half molecules in gel-overlay assays. When screened by NMR and ITC for interacting with S100P, four chemically synthesised peptides show interactions with low micromolar dissociation constants. The two highest affinity peptides significantly inhibit binding of S100P to α,β-tubulin and, when tagged for cellular entry, also inhibit S100P-induced reduction in tubulin polymerisation and S100P-enhancement of COS-7 or HeLa cell migration. A third peptide incapable of interacting with S100P also fails in this respect. Thus S100P can interact directly with two different cytoskeletal filaments to independently enhance cell migration, the most important step in the metastatic cascade.

Tris(1H-benzimidazol-2-ylmeth-yl)amine methanol tris-olvate.

The structure of the tertiary amine tris-(1H-benzimidazol-2-ylmeth-yl)amine (C24H21N7, abbreviated ntb) has been previously reported twice as solvates, namely the monohydrate and the aceto-nitrile-methanol-water (1/0.5/1.5) solvate, both with the tripodal conformation formed via multiple hydrogen bonds. Now, we report the tri-methanol adduct, ntb·3CH3OH, where the amine has the stair conformation featuring one benzimidazole group oriented in the opposite direction from the other two. The asymmetric unit contains one-half amine, completed through the mirror plane m in space group Pmn21 to form the ntb mol-ecule, with the H atom for each imidazole moiety equally disordered between both N sites available in the imidazole ring. The asymmetric unit also contains one and a half methanol mol-ecules, one being placed in general position with the hy-droxy H atom disordered over two sites with occupancy ratio 1:1, while the other lies on the m mirror plane, and has thus its hy-droxy H atom disordered by symmetry. As in the previously reported solvates, all imine and amine groups of the ntb mol-ecules and the methanol mol-ecules are involved in N-H⋯O and O-H⋯N hydrogen bonds. In the title compound, however, the involved H atom is systematically a disordered H atom provided by an imidazole group or a methanol mol-ecule.

A new pseudopolymorph of perchlorinated neo-penta-silane: the benzene monosolvate Si(SiCl3)4·C6H6.

A new pseudopolymorph of dodeca-chloro-penta-silane, namely a benzene monosolvate, Si5Cl12·C6H6, is described. There are two half mol-ecules of each kind in the asymmetric unit. Both Si5Cl12 mol-ecules are completed by crystallographic twofold symmetry. One of the benzene mol-ecules is located on a twofold rotation axis with two C-H groups located on this rotation axis. The second benzene mol-ecule has all atoms on a general position: it is disordered over two equally occupied orientations. No directional inter-actions beyond normal van der Waals contacts occur in the crystal.