Certain Sufficient Conditions for Starlikeness and Convexity of Meromorphically Multivalent Functions

In this paper we derive certain sufficient conditions for starlikeness and convexity of order α of meromorphically multivalent functions in the punctured unit disk.     

Glycopolymer Brushes for Specific Lectin Binding by Controlled Multivalent Presentation of N‐Acetyllactosamine Glycan Oligomers

A new multivalent glycopolymer platform for lectin recognition is introduced in this work by combining the controlled growth of glycopolymer brushes with highly specific glycosylation reactions. Glycopolymer brushes, synthetic polymers with pendant saccharides, are prepared by surface‐initiated atom transfer radical polymerization (SI‐ATRP) of 2‐O‐(N‐acetyl‐β‐d ‐glucosamine)ethyl methacrylate (GlcNAcEMA). Here, the fabrication of multivalent glycopolymers consisting of poly(GlcNAcEMA) is reported with additional biocatalytic elongation of the glycans directly on the silicon substrate by specific glycosylation using recombinant glycosyltransferases. The bioactivity of the surface‐grafted glycans is investigated by fluorescence‐linked lectin assay. Due to the multivalency of glycan ligands, the glycopolymer brushes show very selective, specific, and strong interactions with lectins. The multiarrays of the glycopolymer brushes have a large potential as a screening device to define optimal‐binding environments of specific lectins or as new simplified diagnostic tools for the detection of cancer‐related lectins in blood serum.

     

Rational Design of a DNA-Scaffolded High-Affinity Binder for Langerin

Binders of langerin could target vaccines to Langerhans cells for improved therapeutic effect. Since langerin has low affinity for monovalent glycan ligands, highly multivalent presentation has previously been key for targeting. Aiming to reduce the amount of ligand required, we rationally designed molecularly defined high-affinity binders based on the precise display of glycomimetic ligands (Glc2NTs) on DNA-PNA scaffolds. Rather than mimicking langerin's homotrimeric structure with a C3-symmetric scaffold, we developed readily accessible, easy-to-design bivalent binders. The method considers the requirements for bridging sugar binding sites and statistical rebinding as a means to both strengthen the interactions at single binding sites and amplify the avidity enhancement provided by chelation. This gave a 1150-fold net improvement over the affinity of the free ligand and provided a nanomolar binder (IC₅₀=300 nM) for specific internalization by langerin-expressing cells.     

Multivalent-Interaction-Driven Assembly of Discrete,Flexible, and Asymmetric Supramolecular Protein Nano-Prisms

Current approaches to design monodisperse protein assemblies require rigid, tight, and symmetric interactions between oligomeric protein units. Herein, we introduce a new multivalent-interaction-driven assembly strategy that allows flexible, spaced, and asymmetric assembly between protein oligomers. We discovered that two polygonal protein oligomers (ranging from triangle to hexagon) dominantly form a discrete and stable two-layered protein prism nanostructure via multivalent interactions between fused binding pairs. We demonstrated that protein nano-prisms with long flexible peptide linkers (over 80 amino acids) between protein oligomer layers could be discretely formed. Oligomers with different structures could also be monodispersely assembled into two-layered but asymmetric protein nano-prisms. Furthermore, producing higher-order architectures with multiple oligomer layers, for example, 3-layered nano-prisms or nanotubes, was also feasible.     

Synthesis of Multivalent Galactosides as Targeting Ligand for Gene Delivery

A series of novel bifunctional glycolipid ligands designed to bind with high affinity and specificity to the asialoglycoprotein receptor (ASGP-R) has been synthesized and assayed in vitro on human hepatoma cells, HepG2, derived from parenchymal liver cells. The compounds bear five β-linked Gal moieties linked to the core scaffold, hexa-antennary alcohol, for interaction with the binding site of the ASGP-R. The liposome/DNA complexes containing the glycolipid ligands are efficiently recognized by ASGP-R and exhibited high affinity and transfection activity.     

Polymer therapeutics: concepts and applications

Polymer therapeutics encompass polymer-protein conjugates, drug-polymer conjugates, and supramolecular drug-delivery systems. Numerous polymer-protein conjugates with improved stability and pharmacokinetic properties have been developed, for example, by anchoring enzymes or biologically relevant proteins to polyethylene glycol components (PEGylation). Several polymer-protein conjugates have received market approval, for example the PEGylated form of adenosine deaminase. Coupling low-molecular-weight anticancer drugs to high-molecular-weight polymers through a cleavable linker is an effective method for improving the therapeutic index of clinically established agents, and the first candidates have been evaluated in clinical trials, including, N-(2-hydroxypropyl)methacrylamide conjugates of doxorubicin, camptothecin, paclitaxel, and platinum(II) complexes. Another class of polymer therapeutics are drug-delivery systems based on well-defined multivalent and dendritic polymers. These include polyanionic polymers for the inhibition of virus attachment, polycationic complexes with DNA or RNA (polyplexes), and dendritic core-shell architectures for the encapsulation of drugs. In this Review an overview of polymer therapeutics is presented with a focus on concepts and examples that characterize the salient features of the drug-delivery systems.     

Multivalent Sialosides: A Tool to Explore the Role of Sialic Acids in Biological Processes

Sialic acids (Sias) are fascinating nine‐carbon monosaccharides that are primarily found on the terminus of the oligosaccharide chains of glycoproteins and glycolipids on cell surfaces. These Sias undergo a variety of structural modifications at their hydroxy and amine positions, thereby resulting in structural diversity and, hence, coordinating a variety of biological processes. However, deciphering the structural functions of such interactions is highly challenging, because the monovalent binding of Sias is extremely weak. Over the last decade, several multivalent Sia ligands have been synthesized to modulate their binding affinity with proteins/lectins. In this Minireview, we highlight recent developments in the synthesis of multivalent Sia probes and their potential applications. We will discuss four key multivalent families, that is, polymers, dendrimers, liposomes, and nanoparticles, and will emphasize the major parameters that are essential for the specific interactions of these molecules with proteins in biological systems.     

Inclusion relationships and argument properties for certain subclasses of multivalent functions associated with a family of linear operators

By making use of a general linear operator , the authors introduce several new subclasses of multivalent functions and investigate various inclusion relationships and argument properties associated with these subclasses. Some interesting applications involving such and other families of linear operators are also considered. The results presented here include a number of known results as their special cases.