Probing Polymer Chain Conformation and Fibril Formation of Peptide Conjugates

Abstract

Covalent conjugates between a synthetic polymer and a peptide hormone were used to probe the molecular extension of these macromolecules and how the polymer modifies the fibril formation of the hormone. NMR spectroscopy of N labeled parathyroid hormone (PTH) was employed to visualize the conformation of the conjugated synthetic polymer, triggered by small temperature changes via its lower critical solution temperature. A shroud-like polymer conformation dominated the molecular architecture of the conjugated chimeras. PTH readily forms amyloid fibrils, which is probably the physiological storage form of the hormone. The polyacrylate based polymers stimulated the nucleation processes of the peptide.

Antimicrobial Polymer–Peptide Conjugates Based on Maximin H5 and PEG to Prevent Biofouling of E. coli and P. aeruginosa

“…Since the peptide utilized in these experiments (i.e., MH5C-Cys) has a molecular weight of 2126 Da and the PEG used has a molecular weight of 2 and 5 kDa, an increase in the molecular weight is expected for the peptides-conjugates (e.g., 2126 (MH5C-Cys) + 2000 Da= 4126 Da). Indeed, results in Figure C show a displacement to the right for the peptides-conjugates, which correspond to an increase in the molecular weights …”

“…Indeed, results in Figure 2C show a displacement to the right for the peptidesconjugates, which correspond to an increase in the molecular weights. 54 After the synthesis of the polymer−peptide conjugates, MIC values were determined at 40 μM for both conjugates (Figures S13 and S14). Futhermore, to investigate whether the conjugates of MH5C-Cys and PEG polymer were able to retain the preventive antimicrobial efficacy, bacterial growth curves and SEM images with both bacteria strains were performed.…”

Bioinspired synthetic polymers-based inhibitors of Alzheimer's amyloid-β peptide aggregation

“…14,56 As demonstrated recently amphiphilic polymers bearing hydrophobic end-groups can significantly change Aβ fibrillation. [57][58][59][60][61] Over the past decades, significant efforts have been made to identify effective strategies and clinical agents for AD treatment, although factual progress is limited. An alternative disease-modifying therapy is to design inhibitors which can delay AD progression via (i) preventing the generation of Aβ by blocking the APP expression and stopping its proteolytic cleavage, or (ii) inhibiting the nucleation-growth of Aβ and removing different aggregates (oligomer intermediates or fibrils).…”

In-Cell NMR: Analysis of Protein–Small Molecule Interactions, Metabolic Processes, and Protein Phosphorylation

“…This posttranslational modification prevented in cellulo activation of PTH receptors 1 and 2 [104], which are G-protein-coupled receptors and drug targets for osteoporosis treatment [115]. PTH consists of three distinct functional regions: residues 1–17 are responsible for activation of the PTH receptors, residues ~18–34 facilitate binding to the extracellular domain (ECD) of the class B G protein coupled receptor [117,118,119], and the role of the intrinsically disordered residues ~34–84 might relate to the formation of functional PTH amyloids as a storage form of the hormone in secretory granules, which is currently under debate [120,121]. Our finding that phosphorylated PTH can still bind to the ECD of the PTH receptor without activation is in line with the recently reported crystal structure of the PTH1 receptor in complex with a PTH variant [115], where the N-terminus of PTH binds deeply into the trans-membrane domain of the receptor, probably resulting in the distortion of the domain by the three negative charges of phosphorylated serines 1,2, and 17.…”