Ethyl({[acryloyl(furan-2-ylmethyl)amino]acetyl}amino)acetate

Ethyl({[acryloyl(furan-2-ylmethyl)amino]acetyl}amino)acetate was synthesized via Ugi four component (4C) reaction at ambient temperature. The protocol employs a reaction between formaldehyde, furfurylamine, acrylic acid, and ethyl 2-isocyanoacetate. The course of the reaction was found to be high yielding, and the resulting glycine ester derivative was well characterized by elemental analysis, FTIR, NMR spectroscopy, and mass spectrometric techniques. © 2017 by the authors; licensee MDPI, Basel, Switzerland.DE-AC02-05CH11231, DOE, U.S. Department of Energy; MŠMT, Ministerstvo Školství, Mládeže a TělovýchovyMSMT CR-USA Kontakt II [LH14050]; Molecular Foundry, Office of Science, Office of Basic Energy Sciences, of the U.S. Department of Energy [DE-AC02-05CH11231]; Ministry of Education, Youth and Sports of the Czech Republic - NPU Program I [LO1504

Solid-phase Submonomer Synthesis of Peptoid Polymers and their Self-Assembly into Highly-Ordered Nanosheets

Peptoids are a novel class of biomimetic, non-natural, sequence-specific heteropolymers that resist proteolysis, exhibit potent biological activity, and fold into higher order nanostructures. Structurally similar to peptides, peptoids are poly N-substituted glycines, where the side chains are attached to the nitrogen rather than the alpha-carbon. Their ease of synthesis and structural diversity allows testing of basic design principles to drive de novo design and engineering of new biologically-active and nanostructured materials

Thermodynamic and Kinetic Parameters for Calcite Nucleation on Peptoid and Model Scaffolds:A Step toward Nacre Mimicry

The production of novel composite materials, assembled using biomimetic polymers known as peptoids (N-substituted glycines) to nucleate CaCO3, can open new pathways for advanced material design. However, a better understanding of the heterogeneous CaCO3 nucleation process is a necessary first step. We determined the thermodynamic and kinetic parameters for calcite nucleation on self-assembled monolayers (SAMs) of nanosheet-forming peptoid polymers and simpler, alkanethiol analogues. We used nucleation rate studies to determine the net interfacial free energy (γ net) for the peptoid-calcite interface and for SAMs terminated with carboxyl headgroups, amine headgroups, or a mix of the two. We compared the results with γ net determined from dynamic force spectroscopy (DFS) and from density functional theory (DFT), using COSMO-RS simulations. Calcite nucleation has a lower thermodynamic barrier on the peptoid surface than on carboxyl and amine SAMs. From the relationship between nucleation rate (J 0) and saturation state, we found that under low-saturation conditions, i.e. <3.3 (pH 9.0), nucleation on the peptoid substrate was faster than that on all of the model surfaces, indicating a thermodynamic drive toward heterogeneous nucleation. When they are taken together, our results indicate that nanosheet-forming peptoid monolayers can serve as an organic template for CaCO3 polymorph growth

Discovery of Stable and Selective Antibody Mimetics from Combinatorial Libraries of Polyvalent, Loop-Functionalized Peptoid Nanosheets.

The ability of antibodies to bind a wide variety of analytes with high specificity and high affinity makes them ideal candidates for therapeutic and diagnostic applications. However, the poor stability and high production cost of antibodies have prompted exploration of a variety of synthetic materials capable of specific molecular recognition. Unfortunately, it remains a fundamental challenge to create a chemically diverse population of protein-like, folded synthetic nanostructures with defined molecular conformations in water. Here we report the synthesis and screening of combinatorial libraries of sequence-defined peptoid polymers engineered to fold into ordered, supramolecular nanosheets displaying a high spatial density of diverse, conformationally constrained peptoid loops on their surface. These polyvalent, loop-functionalized nanosheets were screened using a homogeneous Förster resonance energy transfer (FRET) assay for binding to a variety of protein targets. Peptoid sequences were identified that bound to the heptameric protein, anthrax protective antigen, with high avidity and selectivity. These nanosheets were shown to be resistant to proteolytic degradation, and the binding was shown to be dependent on the loop display density. This work demonstrates that key aspects of antibody structure and function-the creation of multivalent, combinatorial chemical diversity within a well-defined folded structure-can be realized with completely synthetic materials. This approach enables the rapid discovery of biomimetic affinity reagents that combine the durability of synthetic materials with the specificity of biomolecular materials

Aβ40 Oligomers Identified as a Potential Biomarker for the Diagnosis of Alzheimer's Disease

Alzheimer's Disease (AD) is the most prevalent form of dementia worldwide, yet the development of therapeutics has been hampered by the absence of suitable biomarkers to diagnose the disease in its early stages prior to the formation of amyloid plaques and the occurrence of irreversible neuronal damage. Since oligomeric Aβ species have been implicated in the pathophysiology of AD, we reasoned that they may correlate with the onset of disease. As such, we have developed a novel misfolded protein assay for the detection of soluble oligomers composed of Aβ x-40 and x-42 peptide (hereafter Aβ40 and Aβ42) from cerebrospinal fluid (CSF). Preliminary validation of this assay with 36 clinical samples demonstrated the presence of aggregated Aβ40 in the CSF of AD patients. Together with measurements of total Aβ42, diagnostic sensitivity and specificity greater than 95% and 90%, respectively, were achieved. Although larger sample populations will be needed to confirm this diagnostic sensitivity, our studies demonstrate a sensitive method of detecting circulating Aβ40 oligomers from AD CSF and suggest that these oligomers could be a powerful new biomarker for the early detection of AD