Blended polar/nonpolar peptide conjugate interferes with human insulin amyloid-mediated cytotoxicity.

Insulin, a peptide hormone and a key regulator of blood glucose level, is routinely administered to type-I diabetic patients to achieve the required glycemic control. Insulin aggregation and ensuing amyloidosis has been observed at repeated insulin injection sites and in injectable formulations. The latter occurs due to insulin agglomeration during shipping and storage. Such insulin amyloid leads to enhanced immunogenicity and allow potential attachment to cell membranes leading to cell permeability and apoptosis. Small molecule inhibitors provide useful interruption of this process and inhibit protein misfolding as well as amyloid formation. In this context, we report the propensity of a palmitoylated peptide conjugate to inhibit insulin aggregation and amyloid-mediated cytotoxicity, via designed interference with polypeptide interfacial interactions.

A colored hydrophobic peptide film based on self-assembled two-fold topology.

Structural colors are abundant in nature and bear advantages over pigment-based colors, such as higher durability, brilliance and often physical hydrophobicity, thus underlying their vast potential for technological applications. Recently, biomimetics of complex natural topologies resulting in such effects has been extensively studied, requiring advanced processing and fabrication techniques. Yet, artificial topologies combining structural coloration and hydrophobicity have not been reported. Herein, we present the bottom-up fabrication of short self-assembling peptides as surface covering films, resulting in an easily achievable multilevel morphology of primary structures in a foam-like enclosure, producing structural colors and hydrophobicity. We demonstrate simple techniques allowing controlled coloration of different surfaces while maintaining an >100° water contact angle (WCA). The new artificial topology is much simpler than the natural counterparts and is not limited to a specific peptide, thus allowing the design of modular materials with unparalleled multifunctionalities and potential for further tuning and modifications.

Supramolecular Photoactivatable Anticancer Hydrogels.

A photoactivatable dopamine-conjugated platinum(IV) anticancer complex (Pt-DA) has been incorporated into G-quadruplex G4K+ borate hydrogels by using borate ester linkages (Pt-G4K+B hydrogel). These were characterized by 11B NMR, attenuated total reflection Fourier transform infrared spectroscopy, circular dichroism, scanning electron microscopy and transmission electron microscopy. Microscopy investigations revealed the transformation of an extended fiber assembly into discrete flakes after incorporation of Pt-DA. Pt-DA showed photocytotoxicity against cisplatin-resistant A2780Cis human ovarian cancer cells (IC50 74 µM, blue light) with a photocytotoxic index <2, whereas Pt-G4K+B hydrogels exhibited more potent photocytotoxicity (IC50 3 µM, blue light) with a photocytotoxic index >5. Most notably, Pt-DA and Pt-G4K+B hydrogels show selective phototoxicity for cancer cells versus normal fibroblast cells (MRC5).

Controlling in Vitro Insulin Amyloidosis with Stable Peptide Conjugates: A Combined Experimental and Computational Study.

Insulin aggregation, to afford amyloidogenic polypeptide fibrils, is an energetically driven, well-studied phenomenon, which presents interesting biological ramifications. These aggregates are also known to form around insulin injection sites and in diabetic patients suffering from Parkinson's disease. Such occurrences force considerable reduction in hormone activity and are often responsible for necrotic deposits in diabetic patients. Changes in physicochemical environment, such as pH, temperature, ionic strength, and mechanical agitation, affect insulin fibrillation, which also presents intrigue from the structural viewpoint. Several reports have tried to unravel underlying mechanisms concerning the aggregation process taking into account a three aromatic amino acid patch Phe(B24)-Phe(B25)-Tyr(B26) located in the C-terminal part of the B chain, identified as a key site for human insulin-receptor interaction. The present study describes design and inhibitory effects of novel peptide conjugates toward fibrillation of insulin as investigated by thioflavin T assay, circular dichroism, and AFM. Possible interaction of insulin with peptide-based fibrillation inhibitors reveals an important role of hydrophobic interactions in the inhibition process. Molecular dynamics simulation studies demonstrate that inhibitor D4 interacts with insulin residues from the helix and the C-terminal extended segment of chain B. These studies present a novel approach for the discovery of stable, peptide-based ligands as novel antiamyloidogenic agents for insulin aggregation.

Thermoplasmonic effect of silver nanoparticles modulates peptide amphiphile fiber into nanowreath-like assembly.

This study demonstrates the beneficial role of di-tryptophan containing short peptide amphiphiles (sPA), for the synthesis and stabilization of AgNPs in the presence of sunlight followed by garlanding of AgNPs along the fibrous network of sPA. Such hybrid structures were precisely and selectively moulded into a nanowreath-type morphology due to the thermoplasmonic effect of AgNPs, and can be used for several bio-nanotechnological applications.

Inhibition of human and bovine insulin fibril formation by designed peptide conjugates.

The aggregation of insulin, to afford amyloidogenic fibers, is a well-studied phenomenon, which has interesting biological ramifications and pharmaceutical implications. These fibers have been ascribed an intriguing role in certain disease states and stability of pharmaceutical formulations of this hormone. The present study describes the design and inhibitory effects of novel peptide conjugates toward fibrillation of insulin as investigated by thioflavin T assay, circular dichroism (CD), and atomic force microscopy (AFM). Possible interaction of insulin with peptide-based fibrillation inhibitors is also probed by other solution phase studies, which reveal an important role of aromatic π-π interactions in the inhibition process. CD studies suggest that a freshly prepared solution of insulin, rich in α-helices, transforms into a ß-sheet structure upon aggregation, which gets perturbed in the presence of synthesized inhibitors. Therefore, these newly designed peptides could serve as potential leads as inhibitors of insulin aggregation.