Supramolecular Synthons in Protein-Ligand Frameworks.

Supramolecular synthons, defined as reproducible intermolecular structural units, have greatly aided small molecule crystal engineering. In this paper, we propose that supramolecular synthons guide ligand-mediated protein crystallization. The protein RSL and the macrocycle sulfonato-calix[8]arene cocrystallize in at least four ways.

Multivalent Calixarene Complexation of a Designed Pentameric Lectin.

We describe complex formation between a designed pentameric β-propeller and the anionic macrocycle sulfonato-calix[8]arene (), as characterized by X-ray crystallography and NMR spectroscopy. Two crystal structures and N HSQC experiments reveal a single calixarene binding site in the concave pocket of the β-propeller toroid. Despite the symmetry mismatch between the pentameric protein and the octameric macrocycle, they form a high affinity multivalent complex, with the largest protein-calixarene interface observed to date.

Protein-macrocycle polymorphism: crystal form IV of the Ralstonia solanacearum lectin-sulfonato-calix[8]arene complex.

Controlled protein assembly and crystallization is necessary as a means of generating diffraction-quality crystals as well as providing a basis for new types of biomaterials. Water-soluble calixarenes are useful mediators of protein crystallization. Recently, it was demonstrated that Ralstonia solanacearum lectin (RSL) co-crystallizes with anionic sulfonato-calix[8]arene (sclx) in three space groups.

Cage versus sheet: Probing the Determinants of Protein - Cucurbit[7]uril Crystalline Architectures.

The donut-shaped cucurbit[n]urils (Qn) are a class of rigid macrocyclic receptor with protein recognition capabilities. Qn encapsulation of amino acid side chains can enable protein assembly. Recently, cucurbit[7]uril (Q7) has been applied as a molecular glue for organizing protein building blocks into crystalline architectures.

Where is the Macrocycle? Comment on "Simultaneous Organic and Inorganic Host-Guest Chemistry within Pillararene-Protein Cage Frameworks.".

Kostiainen and co-workers claim to have prepared crystals of ferritin by "electrostatically bridging" the protein with a cationic pillar[5]arene. Questions remain regarding the contribution of the pillar[5]arene to protein assembly and the putative role as a molecular glue.

Solid-state NMR - a complementary technique for protein framework characterization.

Protein frameworks are an emerging class of biomaterial with medical and technological applications. Frameworks are studied mainly by X-ray diffraction or scattering techniques. Complementary strategies are required.

Complex Formation between Cytochrome and a Tetra-alanino-calix[4]arene.

Owing to their remarkable features, calix[n]arenes are being exploited to study different aspects of molecular recognition, including protein complexation. Different complexation modes have been described, depending on the moieties that complement the aromatic cavity, allowing for function regulation and/or controlled assembly of the protein target. Here, a rigid cone calix[4]arene, bearing four anionic alanine units at the upper rim, was tested as a ligand for cytochrome .

Molecular characterization of accripin11, a soluble shell protein with an acidic C-terminus, identified in the prismatic layer of the Mediterranean fan mussel Pinna nobilis (Bivalvia, Pteriomorphia).

We have identified a novel shell protein, accripin11, as a major soluble component of the calcitic prisms of the fan mussel Pinna nobilis. Initially retrieved from a cDNA library, its full sequence is confirmed here by transcriptomic and proteomic approaches. The sequence of the mature protein is 103 residues with a theoretical molecular weight of 11 kDa and is moderately acidic (pI 6.

Protein-Calixarene Complexation: From Recognition to Assembly.

This Account summarizes the progress in protein-calixarene complexation, tracing the developments from binary recognition to the activity of calixarenes and beyond to macrocycle-mediated frameworks. During the past 10 years, we have been tackling the question of protein-calixarene complexation in several ways, mainly by cocrystallization and X-ray structure determination as well as by solution state methods, NMR spectroscopy, isothermal titration calorimetry (ITC), and light scattering. Much of this work benefitted from collaboration, highlighted here.

Protein Frameworks with Thiacalixarene and Zinc.

Controlled protein assembly provides a means to generate biomaterials. Synthetic macrocycles such as the water-soluble sulfonato-calix[n]arenes are useful mediators of protein assembly. Sulfonato-thiacalix[4]arene ( ), with its metal-binding capacity, affords the potential for simultaneous macrocycle- and metal-mediated protein assembly.

Development of a Multiplex Tandem PCR (MT-PCR) Assay for the Detection of Emerging SARS-CoV-2 Variants.

The emergence of variants of SARS-CoV-2 has created challenges for the testing infrastructure. Although large-scale genome sequencing of SARS-CoV-2 has facilitated hospital and public health responses, access to sequencing facilities globally is variable and turnaround times can be significant, so there is a requirement for rapid and cost-effective alternatives. Applying a polymerase chain reaction (PCR)-based single nucleotide polymorphism (SNP) approach enables rapid (<4 h) identification of SARS-CoV-2 lineages from nucleic acid extracts, through the presence or absence of a panel of defined of genomic polymorphisms.

Segregated Protein-Cucurbit[7]uril Crystalline Architectures via Modulatory Peptide Tectons.

One approach to protein assembly involves water-soluble supramolecular receptors that act like glues. Bionanoarchitectures directed by these scaffolds are often system-specific, with few studies investigating their customization. Herein, the modulation of cucurbituril-mediated protein assemblies through the inclusion of peptide tectons is described.

The nuclear kinesin KIF18B promotes 53BP1-mediated DNA double-strand break repair.

53BP1 is recruited to chromatin in the vicinity of DNA double-strand breaks (DSBs). We identify the nuclear kinesin, KIF18B, as a 53BP1-interacting protein and define its role in 53BP1-mediated DSB repair. KIF18B is a molecular motor protein involved in destabilizing astral microtubules during mitosis.

The Effect of Lidocaine and Bosutinib on 4T1 Murine Breast Cancer Cell Behaviour .

Background/aim: Systemic lidocaine has recently emerged as a promising agent possessing numerous potentially anti-neoplastic effects. In vitro studies suggest that lidocaine may prevent metastasis by acting on the tyrosine kinase enzyme Src. Intravenous lidocaine has been reported to reduce pulmonary metastasis in vivo in a murine breast cancer model, however the beneficial effect is abolished by the Src inhibitor bosutinib.

Noncovalent Protein-Pseudorotaxane Assembly Incorporating an Extended Arm Calix[8]arene with α-Helical Recognition Properties.

Water-soluble, anionic calix[]arenes are useful receptors for protein recognition and assembly. For example, sulfonato-calix[8]arene ( ) can encapsulate proteins and direct their assembly into porous frameworks. In this work, we turned our attention to an "extended arm" calixarene with 16 phenyl rings.

Porous assembly of an antifungal protein mediated by zinc and sulfonato-calix[8]arene.

Controlled protein assembly holds great potential in the fabrication of biohybrid materials. However, the structural diversity and complexity of proteins present an obstacle to controlled assembly. Supramolecular chemistry is a possible solution as it offers tools to mediate self-assembly with molecular precision.

Facile Fabrication of Protein-Macrocycle Frameworks.

Precisely defined protein aggregates, as exemplified by crystals, have applications in functional materials. Consequently, engineered protein assembly is a rapidly growing field. Anionic calix[n]arenes are useful scaffolds that can mold to cationic proteins and induce oligomerization and assembly.

Protein recognition by cucurbit[6]uril: high affinity N-terminal complexation.

The donut-shaped cucurbit[n]urils (Qn, n = 6-8) are rigid macrocyclic receptors with widespread use in protein recognition. To date, most applications have centred on the encapsulation of N-terminal aromatic residues by Q7 or Q8. Less attention has been placed on Q6, which can recognize lysine side chains due to its high affinity for alkylamines.

The surgical management of metastatic pancreatic acinar cell carcinoma and associated pancreatic panniculitis-A case report and literature review.

Introduction: Pancreatic panniculitis is a rare manifestation of benign and malignant pancreatic disease. The presentation of pancreatic panniculitis is non-specific and thus diagnosis is often delayed. When associated with malignancy, pancreatic panniculitis confers a poor prognosis.

Engineered assembly of a protein-cucurbituril biohybrid.

A crystalline biohybrid with a 4 : 1 protein : cucurbituril mass ratio is presented. This result was achieved by engineering additional cucurbit[7]uril (Q7) binding sites into a β-propeller protein. In contrast to the parent protein, Q7-controlled assembly of the engineered variant occurred in solution, as evidenced by NMR and SAXS measurements.

Probing the determinants of porosity in protein frameworks: co-crystals of cytochrome c and an octa-anionic calix[4]arene.

Sulfonato-calix[n]arenes (sclxn) are promising tools to generate crystalline protein frameworks. We report, for the first time, a lower rim functionalised octa-anionic calix[4]arene (sclx4mc) in complex with proteins. Two crystal structures of sclx4mc bound to yeast or horse heart cytochrome c (cytc) are described.

Effects of Lidocaine and Src Inhibition on Metastasis in a Murine Model of Breast Cancer Surgery.

Breast cancer recurs in 20% of patients following intended curative resection. In vitro data indicates that amide local anaesthetics, including lidocaine, inhibit cancer cell metastasis by inhibiting the tyrosine kinase enzyme Src. In a murine breast cancer surgery model, systemic lidocaine reduces postoperative pulmonary metastases.

Tuning Protein Frameworks via Auxiliary Supramolecular Interactions.

Protein crystals with their precise, periodic array of functional building blocks have potential applications in biomaterials, sensing, and catalysis. This paper describes how a highly porous crystalline framework of a cationic redox protein and an anionic macrocycle can be modulated by a small cationic effector. Ternary composites of protein (∼13 kDa), calix[8]arene (∼1.

Crystal structure of a protein-aromatic foldamer composite: macromolecular chiral resolution.

Co-crystallization of a 2 kDa tether-free sulfonated foldamer and the 13 kDa lysine-rich cytochrome c yielded a remarkable biohybrid assembly with chiral resolution of the foldamer helix handedness. In the crystal a ∼5 nm foldamer stack was surrounded by eight molecules of protein. NMR and CD experiments suggest interesting differences in the solution state recognition processes.