Investigation of the Hydration State of Self-Assembled Peptide Nanostructures with Advanced Electron Paramagnetic Resonance Spectroscopy

Abstract

Probing the intermolecular interactions and local environments of self-assembled peptide nanostructures (SPNs) is crucial for a better understanding of the underlying molecular details of self-assembling phenomena. In particular, investigation of the hydration state is important to understand the nanoscale structural and functional characteristics of SPNs. In this report, we examined the local hydration environments of SPNs in detail to understand the driving force of the discrete geometric structural self-assembling phenomena for peptide nanostructures. Advanced electron paramagnetic resonance spectroscopy was used to probe the hydrogen bond formation and geometry as well as the hydrophobicity of the local environments at various spin-labeled sites in SPNs. The experimental results supplement the sparse experimental data regarding local structures of SPNs, such as the hydrogen bonding and the hydrophobicity of the local environment, providing important information on the formation of SPNs, which have immense potential for bioactive materials.

Water Structure and Properties at Hydrophilic and Hydrophobic Surfaces

“…For example, solvent polarity near nitroxide spin labels may be determined by fitting EPR spectra to empirical models and correlating with characteristic hyperfine tensor components of the nitroxide probe (88). Various EPR line-shape analysis techniques, as well as pulsed EPR methods, including electron spin echo envelope modulation (ESEEM) of vitrified samples, can be used to quantify the number of hydrogen bonds of nitroxide moieties to water and water accessibility, or yield information on local polarity, and microviscosities (89)(90)(91)(92).…”

A Joint Venture of Ab Initio Molecular Dynamics, Coupled Cluster Electronic Structure Methods, and Liquid-State Theory to Compute Accurate Isotropic Hyperfine Constants of Nitroxide Probes in Water

“…Electron paramagnetic resonance (EPR) spectroscopy is a robust analysis tool which has found a myriad of applications across many disciplines. − The microscopic understanding of experimental EPR signals is necessary to infer structural information of systems under investigation. EPR experiments in aqueous solutions are particularly interesting as hydration plays an important role in a wealth of diverse phenomena involving species with unpaired electrons. − Thus, it is important to understand the link between microscopic solvation and EPR signals at the molecular level. Fundamentally, theoretical methods can dig out what is hidden behind the numbers obtained from experiments that reflect an average of a distribution of microscopic states.…”

Combination of peptides with biological, organic, and inorganic materials for synergistically enhanced diagnostics and therapeutics

“…[41,42] One promising strategy to address this issue is the development of peptide-fatty acid conjugates; fatty acid mediates the physical binding of the PBC to serum albumin after administration and, in turn, significantly enhances biological half-life of the peptide. GRGDS β-glucan [20] GFLGC Hyaluronic acid [21] (B) Thiol-reactive reaction KKLFKKILKYLC Tetra(ethylene glycol)-poly(L-lysine) [22] FKRLKKLISWIKRKRQQC DSPE-PEG 3400 [23] CQWKWEWKWEWQ 2,2,6,6-tetramethylpiperidine-1-oxyl [24] (C) Copper free click reaction SPWPRPTY Aptamer [25] MQNMPRLSWNPFCS Peptide (MDEKAQKGPAKLVFFACEKG) [26] [APLPR] 2 -KK Alkyne-terminated electrode [27] (D) Thiol-ene reaction CGGGRGDS Norbornene-modified alginate [28] CGRGDS Methacrylate-modified starch [29] GCGREDVSG Allyl group-modified silicon wafers [30] (E) Reaction with cross linker YGRKKRRQRRR Marine peptide N6 [31] RRRRRRRRR Polyamidoamine dendrimer [32] GLFDIVKKVVGALC Hyperbrancehd polyglycerol [33] (HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS), which activates one of the most effective targets for type-2 diabetic therapy, glucagon-like peptide-1 (GLP-1) receptor (Figure 1A). [43] The exendin-4-lauric acid conjugates were found to have 6.3-fold greater serum stability than single molecular exendin-4 due to the albumin binding (4.03 hours vs 0.64 hour), which translated into fourfold prolonged normoglycemia in vivo.…”