Solid-Phase Synthesis of Asymmetrically Branched Sequence-Defined Poly/Oligo(amidoamines)

We present for the first time the synthesis of asymmetrically branched sequence-defined poly/oligo­(amidoamines) (PAAs) using solid-phase synthesis with the capability of introducing diversity at the side chains. We introduce two new versatile (diethylenetriamine) building blocks for solid-phase synthesis bearing Fmoc/Boc and Fmoc/Alloc protecting groups expanding recently used Fmoc/Boc protecting group strategy for linear PAAs to an Fmoc/Alloc/Boc strategy. This allows for orthogonal on-resin cleavage of Fmoc and Alloc protecting groups during solid-phase synthesis of PAAs with backbones differing in chain length and sequence. With these structures we then demonstrate the potential for generating asymmetrical branching by automated multiple on-resin cleavage of Alloc protecting groups as well as the introduction of side chains varying in length and number. Such systems have high potential as nonviral vectors for gene delivery and will allow for more detailed studies on the correlation between the degree of branching of PAAs and their resulting biological properties

Sequence-Defined Glycopolymer Segments Presenting Mannose: Synthesis and Lectin Binding Affinity

We present for the first time the synthesis of sequence-defined monodisperse glycopolymer segments via solid-phase polymer synthesis. Functional building blocks displaying alkyne moieties and hydrophilic ethylenedioxy units were assembled stepwise on solid phase. The resulting polymer segments were conjugated with mannose sugars via 1,3-dipolar cycloaddition. The obtained mono-, di-, and trivalent mannose structures were then subject to Con A lectin binding. Surface plasmon resonance studies showed a nonlinear increase in binding regarding the number and spacing of sugar ligands. The results of Con A lectin binding assays indicate that the chemical composition of the polymeric scaffold strongly contributes to the binding activities as well as the spacing between the ligands and the number of presented mannose units. Our approach now allows for the synthesis of highly defined glycooligomers and glycopolymers with a diversity of properties to investigate systematically multivalent effects of polymeric ligands

Metal-Mediated Molecular Self-Healing in Histidine-Rich Mussel Peptides

Mussels withstand high-energy wave impacts in rocky seashore habitats by fastening tightly to surfaces with tough and self-healing proteinaceous fibers called byssal threads. Thread mechanical behavior is believed to arise from reversibly breakable metal coordination cross-links embedded in histidine-rich protein domains (HRDs) in the principle load-bearing proteins comprising the fibrous thread core. In order to investigate HRD behavior at the molecular level, we have synthesized a histidine-rich peptide derived from mussel proteins (His₅-bys) and studied its reversible adhesive self-interaction in the presence and absence of metal ions using PEG-based soft-colloidal probes (SCPs). Adhesion energies of greater than 0.3 mJ/m² were measured in the presence of metal ions, and the stiffness of the modified SCPs exhibited a 3-fold increase, whereas no adhesion was observed in the absence of metals. Raman spectroscopy confirmed the presence of metal-coordination via histidine residues by the peptide–supporting the role of His-metal complexes in the mechanical behavior of the byssus

Green Solid-Phase Peptide Synthesis: Oxyma-Triggered Spectrophotometric Monitoring of Residual Piperidine

Solid-phase peptide synthesis (SPPS) is an efficient platform technology for synthesizing synthetic peptides but has an environmental downside due to the use of vast amounts of toxic solvents. In recent years, a big effort has been made to replace these solvents with more environmentally benign alternatives; however, this work has not had a significant effect on reducing the PMI and carbon footprint of SPPS. Herein, we demonstrate that by adding a low concentration of Oxyma Pure to the waste stream after Fmoc-removal, a simple real-time online UV–vis monitoring system can quantify piperidine with the needed sensitivity. In addition to the potential for reducing washing volumes after Fmoc-removal, this inexpensive and easy-to-implement process analytical tool allows the determination of completed washing by visual inspection due to the yellow color of Oxyma Pure in the presence of piperidine. Moreover, manual sampling of the waste stream is not needed, which reduces the overall process time. Importantly, the methodology was found to be compatible with green SPPS performed in 10–50% DMSO in the EtOAc mixtures