Living Materials Constructed with Dynamic Covalent Interface between Synthetic Polymers and B. subtilis

With advances in the field of synthetic biology increasingly allowing us to engineer living cells to perform intricate tasks, incorporating these engineered cells into the design of synthetic polymeric materials will enable programming materials with a wide range of biological functionalities. However, employable strategies for the design of synthetic polymers that form a well-defined interface with living cells and seamlessly integrate their functionalities in materials are still largely limited. Herein, we report the first example of living materials constructed with a dynamic covalent interface between synthetic polymers and living B. subtilis cells. We showedthat 3-acetamidophenylboronic acid (APBA) and polymers of APBA (pAPBA) form dynamic covalent bonds with available diols on the B. subtilis cell surface. Importantly, pAPBA binding to B. subtilis shows a multivalent effect with complete reversibility upon addition of competitive diol species, such as fructose and sorbitol. On the basis of these findings, we constructed telechelic block copolymers with pAPBA chain ends that crosslink B. subtilis cells and produced self- standing living materials. We further demonstrated that the encapsulated cells could be retrieved upon immersing these materials in solutions containing competitive diols and further subjected to biological analyses. This work establishes the groundwork for building a myriad of synthetic polymeric materials integrating engineered living cells and provides a platform for understanding the biology of cells confined within materials.

Carbohydrate supramolecular chemistry: beyond the multivalent effect

(Hetero)multivalency acts as a multichannel switch that shapes the supramolecular properties of carbohydrates in an intrinsically multifactorial biological context.

Conjugation of biphenyl groups with poly(ethylene glycol) to enhance inhibitory effects on the PD-1/PD-L1 immune checkpoint interaction

Inhibitory effect of small molecule immune checkpoint inhibitors on the PD-1/PD-L1 immune checkpoint interaction was enhanced by the multivalent effect through the conjugation of branched PEG.

Development of C-type lectin-oriented surfaces for high avidity glycoconjugates: towards mimicking multivalent interactions on the cell surface

Here we described C-type lectin-oriented surfaces for SPR analysis. They allow the preservation of receptor topology, accessibility of binding sites, better evaluation of high avidity compounds and assessment of multivalent effect at cell surface.

Supramolecular dimerization of a hexameric hemoprotein via multiple pyrene-pyrene interactions

Protein assemblies are being investigated as a new-class of biomaterials. A supramolecular assembly of a mutant hexameric tyrosine coordinated hemoprotein (HTHP) modified with a pyrene derivative is described. Cysteine was first introduced as a site-specific reaction point at position V44 which is located at the bottom surface of the cylindrical structure of HTHP. [Formula: see text]-(1-pyrenyl)maleimide was then reacted with the mutant. The modification was confirmed by MALDI-TOF mass spectrometry and UV-vis absorption spectroscopy, indicating that approximately 90% cysteine residues are attached via the pyrene derivative. Size exclusion chromatography (SEC) measurements for pyrene-attached HTHP include a single peak which elutes earlier than the unmodified HTHP. Further investigation by SEC and dynamic light scattering (DLS) measurements indicate the desired size corresponding to the dimer of the hemoprotein hexamers. The multivalent effect of pyrene–pyrene interactions including hydrophobic and [Formula: see text]–[Formula: see text] stacking interactions appears to be responsible for including formation of the stable dimer of the hexamers. Interestingly, the assembly dissociates to the hexamer by removal of heme. In the case of the apo-form of pyrene-attached HTHP, the pyrene moiety appears to be incorporated into the heme pocket because the modification point is located at the adjacent residue of the Tyr45 coordinating to heme in the holo-form of HTHP. Subsequent addition of heme into the apo-form of pyrene-attached HTHP regenerates the dimer of the hexamers. The present study demonstrates a unique heme-dependent system in which HTHP is assembled to form a dimer of hexamers in the presence of heme and disassembled by removal of heme.

Galactosyl and sialyl clusters: synthesis and evaluation against T. cruzi parasite

The multivalent effect of carbohydrates (glycoclusters) has been explored to study important biological targets and processes involvingTrypanosoma cruzi(T. cruzi) infection. Likewise, CuAAC cycloaddition reactions (click chemistry) have been applied as useful strategy in the discovery of bioactive molecules. Hence, we describe the synthesis of 1,2,3-triazole-based tetravalent homoglycoclusters (1–3) and heteroglycoclusters (4and5) ofd-galactopyranose (C-1 and C-6 positions) and sialic acid (C-2 position) to assess their potential to inhibitT. cruzicell invasion and also its cell surfacetrans-sialidase (TcTS). The target compounds were synthesised in good yields (52–75 %)viaclick chemistry by coupling azidosugars galactopyranose and sialic acid with alkynylated pentaerythritol or tris(hydroxymethyl)-aminomethane (TRIS) scaffolds.T. cruzicell invasion inhibition assays showed expressive low parasite infection index values (5.3–6.8) for most compounds. However, most glycoclusters proved to be weak TcTS inhibitors at 1 mM (<17 %), except the tetravalent sialic acid3(99 % at 1 mM, IC50450 μM). Therefore, we assume thatT. cruzicell invasion blockage is not due to TcTS inhibition by itself, but rather by other mechanisms involved in this process. In addition, all glycoclusters were not cytotoxic and had significant trypanocidal activity upon parasite survival of amastigote forms.

Increase in the apparent intercalation ability of a platinum complex via multivalency by installation into the sidechain of a graft copolymer and observation of structural changes in the intercalated DNA

Pt complexes increase their apparent binding constant by grafting on sidechains of polymer segments via multivalent effect.