4 research outputs found
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/oligoÂ(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 (His<sub>5</sub>-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/m<sup>2</sup> 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