New generations of synthetic biomaterials are being developed at a rapid pace for use as three-dimensional extracellular microenvironments to mimic the regulatory characteristics of natural extracellular matrices (ECMs) and ECM-bound growth factors, both for therapeutic applications and basic biological studies. Recent advances include nanofibrillar networks formed by self-assembly of small building blocks, artificial ECM networks from protein polymers or peptide-conjugated synthetic polymers that present bioactive ligands and respond to cell-secreted signals to enable proteolytic remodeling. These materials have already found application in differentiating stem cells into neurons, repairing bone and inducing angiogenesis. Although modern synthetic biomaterials represent oversimplified mimics of natural ECMs lacking the essential natural temporal and spatial complexity, a growing symbiosis of materials engineering and cell biology may ultimately result in synthetic materials that contain the necessary signals to recapitulate developmental processes in tissue- and organ-specific differentiation and morphogenesis.

https://sisu.ut.ee/sites/default/files/quantum/files/synthetic_biomaterials_as_instructive_extracellular_microenvironments_for_morphogenesis_in_tissue_engineering_lutolf_m.p_hubbell_j.a_2005_0.pdf

Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering

Switches, and Actuators Masahiro Irie,*,† Tuyoshi Fukaminato,‡ Kenji Matsuda, and Seiya Kobatake †Research Center for Smart Molecules, Rikkyo University, Nishi-Ikebukuro 3-34-1, Toshima-ku, Tokyo 171-8501, Japan ‡Research Institute for Electronic Science, Hokkaido University, N20, W10, Kita-ku, Sapporo 001-0020, Japan Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan Department of Applied Chemistry, Graduate School of Engineering, Osaka City University, Sugimoto 3-3-138, Sumiyoshi-ku, Osaka 558-8585, Japan

Photochromism of Diarylethene Molecules and Crystals: Memories, Switches, and Actuators

In recent years there has been immense interest in studying gels derived from low molecular mass gelators (supramolecular, or simply molecular gels). The motivation for this is not only to understand the fundamental aggregate structures in the gels at different length scales, but also to explore their potential for futuristic technological applications. Gels have been made sensitive to external stimuli like light and chemical entities by incorporating a spectroscopically active or a receptor unit as part of the gelator molecule. This makes them suitable for applications such as sensing and actuating. The diversity of gel structural architectures has allowed them to be utilized as templates to prepare novel inorganic superstructures for possible applications in catalysis and separation. Gels derived from liquid crystals (anisotropy gels) that can act as dynamically functional materials have been prepared, for example, for (re-writable) information recording. Supramolecular gels can be important in controlled release applications, in oil recovery, for gelling cryogenic fuels etc. They can also serve as media for a range of applications. This tutorial review highlights some of the instructive work done by various groups to develop smart and functional gels, and covers a wide spectrum of scientific interest ranging from medicine to materials science.

/pdf/supramolecular-gels-functions-and-uses-51lemkjn44.pdf

Supramolecular gels: Functions and uses

Functional π-Gelators and Their Applications

The Diels-Alder reaction has both enabled and shaped the art and science of total synthesis over the last few decades to an extent which, arguably, has yet to be eclipsed by any other transformation in the current synthetic repertoire. With myriad applications of this magnificent pericyclic reaction, often as a crucial element in elegant and programmed cascade sequences facilitating complex molecule construction, the Diels-Alder cycloaddition has afforded numerous and unparalleled solutions to a diverse range of synthetic puzzles provided by nature in the form of natural products. In celebration of the 100th anniversary of Alder's birth, selected examples of the awesome power of the reaction he helped to discover are discussed in this review in the context of total synthesis to illustrate its overall versatility and underscore its vast potential which has yet to be fully realized.

https://www.ch.ic.ac.uk/local/organic/pericyclic/DA.pdf

The Diels--Alder reaction in total synthesis.

The protein microarray is a crucial biomaterial for the rapid and high-throughput assay of many biological events where proteins are involved. In contrast to the DNA microarray, it has not been sufficiently established because of protein instability under the conventional dry conditions. Here we report a novel semi-wet peptide/protein microarray using a supramolecular hydrogel composed of glycosylated amino acetate. The spontaneous gel-formation and amphiphilic properties of this supramolecular hydrogel have been applied to a new type of peptide/protein gel array that is compatible with enzyme assays. Aqueous cavities created in the gel matrix are a suitable semi-wet reaction medium for enzymes, whereas the hydrophobic domains of the fibre are useful as a unique site for monitoring the reaction. This array system overcomes several drawbacks of conventional protein chips, and thus can have potential applications in pharmaceutical research and diagnosis.

Semi-wet peptide/protein array using supramolecular hydrogel

1,2-Bis(2-methyl-5-phenyl-3-thienyl)perfluorocyclopentene (1a) and their derivatives, 1,2-bis(2-methyl-5-p-tolyl-3-thienyl)perfluorocyclopentene (2a) and 1,2-bis(2-methyl-5-p-tert-butylphenyl-3-thienyl)perfluorocyclopentene (3a), were found to undergo reversible photochromic reactions in the single-crystalline phase. Upon irradiation with 366 nm light the single crystals turned blue. The blue colored crystals returned to colorless by irradiation with visible light (λ > 480 nm). The substituents at para positions of the phenyl groups did not affect the rates of photocyclization reactions both in the single-crystalline phase and in hexane. Activation energies of the photocyclization reactions were almost zero. On the other hand, activation energies as much as 5−10 kJ mol-1 were observed in the photocycloreversion reactions in the single-crystalline phase. These values were smaller than those observed in solution, ca. 16 kJ mol-1. Slow thermal cycloreversion reaction of the closed-ring isomer (1b) was observ...

Photochromism of 1,2-Bis(2-methyl-5-phenyl-3-thienyl)perfluorocyclopentene in a Single-Crystalline Phase

Fusicoccins are a class of diterpene glucosides produced by the plant-pathogenic fungus Phomopsis amygdali. As modulators of 14-3-3 proteins, fusicoccins function as potent activators of plasma membrane H+-ATPase in plants and also exhibit unique biological activity in animal cells. Despite their well studied biological activities, no genes encoding fusicoccin biosynthetic enzymes have been identified. Cyclic diterpenes are commonly synthesized via cyclization of a C20 precursor, geranylgeranyl diphosphate (GGDP), which is produced through condensation of the universal C5 isoprene units dimethylallyl diphosphate and isopentenyl diphosphate by prenyltransferases. We found that (+)-fusicocca-2,10 (14)-diene, a tricyclic hydrocarbon precursor for fusicoccins, is biosynthesized from the C5 isoprene units by an unusual multifunctional enzyme, P. amygdali fusicoccadiene synthase (PaFS), which shows both prenyltransferase and terpene cyclase activities. The functional analysis of truncated mutants and site-directed mutagenesis demonstrated that PaFS consists of two domains: a terpene cyclase domain at the N terminus and a prenyltransferase domain at the C terminus. These findings suggest that fusicoccadiene can be produced efficiently in the fungus by using the C5 precursors, irrespective of GGDP availability. In fact, heterologous expression of PaFS alone resulted in the accumulation of fusicocca-2,10 (14)-diene in Escherichia coli cells, whereas no product was detected in E. coli cells expressing Gibberella fujikuroi ent-kaurene synthase, another fungal diterpene cyclase that also uses GGDP as a substrate but does not contain a prenyltransferase domain. Genome walking suggested that fusicoccin biosynthetic enzymes are encoded as a gene cluster near the PaFS gene.

https://www.pnas.org/content/pnas/104/9/3084.full.pdf

Fusicoccins are biosynthesized by an unusual chimera diterpene synthase in fungi

On the scope, mechanism and stereochemistry of the Lewis acid catalyzed cyclocondensation of activated dienes with aldehydes: an application to the erythronolide problem

One-third of all human cancers harbor somatic RAS mutations. This leads to aberrant activation of downstream signaling pathways involving the RAF kinases. Current ATP-competitive RAF inhibitors are active in cancers with somatic RAF mutations, such as BRAFV600 mutant melanomas. However, they paradoxically promote the growth of RAS mutant tumors, partly due to the complex interplay between different homo- and heterodimers of A-RAF, B-RAF, and C-RAF. Based on pathway analysis and structure-guided compound identification, we describe the natural product cotylenin-A (CN-A) as stabilizer of the physical interaction of C-RAF with 14-3-3 proteins. CN-A binds to inhibitory 14-3-3 interaction sites of C-RAF, pSer233, and pSer259, but not to the activating interaction site, pSer621. While CN-A alone is inactive in RAS mutant cancer models, combined treatment with CN-A and an anti-EGFR antibody synergistically suppresses tumor growth in vitro and in vivo. This defines a novel pharmacologic strategy for treatment of ...

Nobuo Kato

Papers

Semi-wet peptide/protein array using supramolecular hydrogel

Photochromism of 1,2-Bis(2-methyl-5-phenyl-3-thienyl)perfluorocyclopentene in a Single-Crystalline Phase

Fusicoccins are biosynthesized by an unusual chimera diterpene synthase in fungi

On the scope, mechanism and stereochemistry of the Lewis acid catalyzed cyclocondensation of activated dienes with aldehydes: an application to the erythronolide problem

Stabilization of Physical RAF/14-3-3 Interaction by Cotylenin A as Treatment Strategy for RAS Mutant Cancers.