Exploring the Potential of Biomimetic Peptides in Targeting Fibrillar and Filamentous Alpha-Synuclein-An In Silico and Experimental Approach to Parkinson's Disease.

Alpha-synuclein (ASyn) is a protein that is known to play a critical role in Parkinson's disease (PD) due to its propensity for misfolding and aggregation. Furthermore, this process leads to oxidative stress and the formation of free radicals that cause neuronal damage. In this study, we have utilized a biomimetic approach to design new peptides derived from marine natural resources.

Design and investigation of novel iridoid-based peptide conjugates for targeting EGFR and its mutants L858R and T790M/L858R/C797S: an in silico study.

In this work, we designed novel peptide conjugates with plant-based iridoid and lichen-derived depside derivatives to target the wild-type EGFR (WT) and its mutants, L858R and T790M/L858R/C797S triple mutant. These mutations are often expressed in multiple cancers, particularly lung cancer. Specifically, the iridoids included 7-deoxyloganetic acid (7-DGA) and loganic acid (LG), while the depside derivative was sekikaic acid (SK).

Design and investigation of interactions of novel peptide conjugates of purine and pyrimidine derivatives with EGFR and its mutant T790M/L858R: an in silico and laboratory study.

Peptide-based therapeutics have been gaining attention due to their ability to actively target tumor cells. Additionally, several varieties of nucleotide derivatives have been developed to reduce cell proliferation and induce apoptosis of tumor cells. In this work, we have developed novel peptide conjugates with newly designed purine analogs and pyrimidine derivatives and explored the binding interactions with the kinase domain of wild-type EGFR and its mutant EGFR [L858R/ T790M] which are known to be over-expressed in tumor cells.

Development of Self-Assembled Biomimetic Nanoscale Collagen-like Peptide-Based Scaffolds for Tissue Engineering: An In Silico and Laboratory Study.

Development of biocomposite scaffolds has gained tremendous attention due to their potential for tissue regeneration. However, most scaffolds often contain animal-derived collagen that may elicit an immunological response, necessitating the development of new biomaterials. Herein, we developed a new collagen-like peptide,(Pro-Ala-His) (PAH), and explored its ability to be utilized as a functional biomaterial by incorporating it with a newly synthesized peptide-based self-assembled gel.

A computational and laboratory approach for the investigation of interactions of peptide conjugated natural terpenes with EpHA2 receptor.

Context: Ephrin type A receptor 2 (EphA2) is a well-known drug target for cancer treatment due to its overexpression in numerous types of cancers. Thus, it is crucial to determine the binding interactions of this receptor with both the ligand-binding domain (LBD) and the kinase-binding domain (KBD) through a targeted approach in order to modulate its activity. In this work, natural terpenes with inherent anticancer properties were conjugated with short peptides YSAYP and SWLAY that are known to bind to the LBD of EphA2 receptor.

Interactions of Nanoscale Self-Assembled Peptide-Based Assemblies with Glioblastoma Cell Models and Spheroids.

Peptide nanoassemblies have garnered remarkable importance in the development of novel nanoscale biomaterials for drug delivery into tumor cells. Taking advantage of receptor mediated recognition of two known peptides, angiopep-2 (TFFYGGSRGKRNNFKTEEY) and A-COOP-K (ACGLSGLC10 VAK) that bind to the over-expressed receptors low density lipoprotein (LRP-1) and fatty acid binding protein (FABP3) respectively, we have developed new peptide conjugates by combining the anti-inflammatory, antitumor compound azelaic acid with angiopep-2, which efficiently self-assembled into nanofibers. Those nanofibers were then functionalized with the A-COOP-K sequence and formed supramolecular hierarchical structures that were found to entrap the chemotherapeutic drug doxorubicin efficaciously.

An investigation of binding interactions of tumor-targeted peptide conjugated polyphenols with the kinase domain of ephrin B4 and B2 receptors.

Recent studies have shown that Ephrin receptors may be upregulated in several types of cancers including breast, ovarian and endometrial cancers, making them a target for drug design. In this work, we have utilized a target-hopping approach to design new natural product-peptide conjugates and examined their interactions with the kinase-binding domain of EphB4 and EphB2 receptors. The peptide sequences were generated through point mutations of the known EphB4 antagonist peptide TNYLFSPNGPIA.

Design of short peptides and peptide amphiphiles as collagen mimics and an investigation of their interactions with collagen using molecular dynamics simulations and docking studies.

Short peptide sequences and bolaamphiphiles derived from natural proteins are gaining importance due to their ability to form unique nanoscale architectures for a variety of biological applications. In this work, we have designed six short peptides (triplet or monomeric forms) and two peptide bolaamphiphiles that either incorporate the bioactive collagen motif (Gly-X-Y) or sequences where Gly, Pro, or hydroxyproline (Hyp) are replaced by Ala or His. For the bolaamphiphiles, a malate moiety was used as the aliphatic linker for connecting His with Hyp to create collagen mimics.

Molecular dynamics, MMGBSA, and docking studies of natural products conjugated to tumor-targeted peptide for targeting BRAF V600E and MERTK receptors.

Recent studies have revealed that MERTK and BRAF V600E receptors have been found to be over-expressed in several types of cancers including melanoma, making these receptors targets for drug design. In this study, we have designed novel peptide conjugates with the natural products vanillic acid, thiazole-2-carboxylic acid, cinnamic acid, theanine, and protocatechuic acid. Each of these compounds was conjugated with the tumor targeting peptide sequence TAASGVRSMH, known to bind to NG2 and target tumor neovasculature.

Molecular dynamics simulations, docking and MMGBSA studies of newly designed peptide-conjugated glucosyloxy stilbene derivatives with tumor cell receptors.

In this work, for the first time, we designed derivatives of beta-D-glucosyloxy-3-hydroxy-trans-stiblene-2-carboxylic acid (GHS), by conjugating GHS with tumor targeting peptides RPARPAR and GGKRPAR to target over-expressed receptors in tumor cells. The sequences RPARPAR and GGKRPAR are known to target the neuropilin1 (NRP1) receptor due to the C-terminal Arg domain; however, their effectiveness has never been examined with other commonly over-expressed receptors in tumor cells, particularly of chronic lymphocytic leukemia that include integrin α1β1 and CD22. By conjugating these peptides with GHS, which is known for its inherent anti-cancer properties, the goal is to further enhance tumor cell targeting by developing compounds that can target multiple receptors.

Molecular dynamics simulations and studies of hybrid decellularized leaf-peptide-polypyrrole composites for potential tissue engineering applications.

Tissue engineering (TE) aims to repair and regenerate damaged tissue by an assimilation of optimal combination of cells specific to the tissue with an appropriate biomaterial. In this work, a new biomaterial for potential cardiac TE applications was developed by utilizing a combination of in silico studies and experiments. Molecular dynamics (MD) simulations for the formation of the novel composite prepared from the decellularized leaf components cellulose and pectin along with the VEGF derived peptide (NYLTHRQ) and polypyrrole (PPy) was carried out to assess self-assembly, mechanical properties, and interactions with integrin and NPR-C receptors which are commonly found in cells of cardiac tissue.

In silico studies of interactions of peptide-conjugated cholesterol metabolites and betulinic acid with EGFR, LDR, and N-terminal fragment of CCKA receptors.

In this work, we designed three new ligands by conjugating cholesterol metabolites 3-hydroxy-5-cholestenoic acid (3-HC) and 3-oxo-4-cholestenoic acid (3-OC) and the natural tri-terpenoid betulinic acid with the tumor-targeting peptide YHWYGYTPQNVI. Molecular interactions with the unconjugated peptide and the conjugates were examined with three receptors that are commonly overexpressed in pancreatic adenocarcinoma cells using ligand docking and molecular dynamics. This study demonstrated the utility of the designed conjugates as a valuable scaffold for potentially targeting EGFR and LDLR receptors.

Alzheimer's Disease: Current Perspectives and Advances in Physiological Modeling.

Though Alzheimer's disease (AD) is the most common cause of dementia, complete disease-modifying treatments are yet to be fully attained. Until recently, transgenic mice constituted most in vitro model systems of AD used for preclinical drug screening; however, these models have so far failed to adequately replicate the disease's pathophysiology. However, the generation of humanized APOE4 mouse models has led to key discoveries.

Exploring the Interactions of Ionic Liquids with Bio-Organic Amphiphiles Using Computational Approaches.

Bio-organic amphiphiles have been shown to effectively impart unique physicochemical properties to ionic liquids resulting in the formation of versatile hybrid composites. In this work, we utilized computational methods to probe the formation and properties of hybrids prepared by mixing three newly designed bio-organic amphiphiles with 14 ionic liquids containing cholinium or glycine betaine cations and a variety of anions. The three amphiphiles were designed such that they contain unique biological moieties found in nature by conjugating (a) malic acid with the amino acid glutamine, (b) thiomalic acid with the antiviral, antibacterial pyrazole compound [3-(3,5-dimethyl-1-pyrazol-1-yl)benzyl]amine, and (c) Fmoc-protected valine with diphenyl amine.

Enhancing Kidney Vasculature in Tissue Engineering-Current Trends and Approaches: A Review.

Chronic kidney diseases are a leading cause of fatalities around the world. As the most sought-after organ for transplantation, the kidney is of immense importance in the field of tissue engineering. The primary obstacle to the development of clinically relevant tissue engineered kidneys is precise vascularization due to the organ's large size and complexity.

Self-Assembled Peptide-Based Biocomposites for Near-Infrared Light Triggered Drug Release to Tumor Cells.

Peptide-based nanomaterials are increasingly gaining popularity due to their specificity, biocompatibility, and biodegradability. In this work, a new multi-layered peptide-based biocomposite for targeting MCF-7 breast cancer cells is developed. The amphipathic Fluorenylmethyloxycarbonyl (Fmoc)-Leu-Ser peptide is synthesized, which is conjugated to a tumor-targeting peptide sequence Gly-Cys-Gly-Asn-Ser to form Fmoc-L-S-G-C-G-N-S (FLS) assemblies.

Development of Nanoscale Hybrids from Ionic Liquid-Peptide Amphiphile Assemblies as New Functional Materials.

Over the years, ionic liquids (ILs) have gained tremendous importance because of their unique properties and plethora of applications. In this work, we have developed a new nanoscale hybrid gel consisting of 1-ethyl-3-methylimidazolium dimethyl phosphate, [Cmim][dmp], and self-assembled peptide nanoassemblies. The peptide nanoassemblies were formed by self-assembly of a newly synthesized peptide bolaamphiphile bis(-α-amido-threonine) 1,7 heptane dicarboxylate (ThrC7).

Varying fish scale derived hydroxyapatite bound hybrid peptide nanofiber scaffolds for potential applications in periodontal tissue regeneration.

New peptide based hybrid scaffolds were prepared by blending two different fish scale derived hydroxyapatite with functionalized peptide nanofibers for potential applications in periodontal tissue regeneration. The nanofibers were prepared by self-assembly of the newly designed peptide bolaamphiphile Bis (N-α-amido-glutamic acid) 1,7 heptane tetracarboxylate and functionalized with a segment of the tyrosine rich amylogenin peptide sequence MPLPPHPGHPGYINF followed by polygalacturnonic acid and hydroxyapatite derived from salmon or red-snapper fish scales. The binding interactions of the components of the scaffold was confirmed by FTIR spectroscopy as well as SEM imaging.

Development of self-assembled phytosterol based nanoassemblies as vehicles for enhanced uptake of doxorubicin to HeLa cells.

Nanoscale supramolecular systems have been increasingly gaining importance as drug release vehicles due to their ability to target tumor cells. In this work, we have developed a new class of nanoassemblies derived from the phytosterol 24-EpiBrassinolide (EpiB) for the development of nanocarriers for the anticancer drug Doxorubicin (DOX). EpiB is a biocompatible cholesterol mimic, and has inherent apoptotic properties toward cancer cells.

Development of Self-Assembled Nanoribbon Bound Peptide-Polyaniline Composite Scaffolds and Their Interactions with Neural Cortical Cells.

Degenerative neurological disorders and traumatic brain injuries cause significant damage to quality of life and often impact survival. As a result, novel treatments are necessary that can allow for the regeneration of neural tissue. In this work, a new biomimetic scaffold was designed with potential for applications in neural tissue regeneration.

Biomineralization of Fucoidan-Peptide Blends and Their Potential Applications in Bone Tissue Regeneration.

Fucoidan (Fuc), a natural polysaccharide derived from brown seaweed algae, and gelatin (Gel) were conjugated to form a template for preparation of biomimetic scaffolds for potential applications in bone tissue regeneration. To the Fuc-Gel we then incorporated the peptide sequence MTNYDEAAMAIASLN (MTN) derived from the E-F hand domain, known for its calcium binding properties. To mimic the components of the extracellular matrix of bone tissue, the Fuc-Gel-MTN assemblies were incubated in simulated body fluid (SBF) to induce biomineralization, resulting in the formation of β-tricalcium phosphate, and hydroxyapatite (HAp).

Multilayered Short Peptide-Alginate Blends as New Materials for Potential Applications in Cartilage Tissue Regeneration.

Peptide based nanomaterials have been gaining increased prominence due to their ability to form permeable scaffolds that promote growth and regeneration of new tissue. In this work for the first time a short hexapeptide motif VQIVYK, derived from the Tau protein family was conjugated with an organic polyamine linker, putrescine and utilized as a template for developing new materials for cartilage tissue regeneration. Our results showed that the conjugate formed extensive nanofibrous assemblies upon self-assembly under aqueous conditions.

Layer-by-layer assembly of peptide based bioorganic-inorganic hybrid scaffolds and their interactions with osteoblastic MC3T3-E1 cells.

In this work we have developed a new family of biocomposite scaffolds for bone tissue regeneration by utilizing self-assembled fluorenylmethyloxycarbonyl protected Valyl-cetylamide (FVC) nanoassemblies as templates. To tailor the assemblies for enhanced osteoblast attachment and proliferation, we incorporated (a) Type I collagen, (b) a hydroxyapatite binding peptide sequence (EDPHNEVDGDK) derived from dentin sialophosphoprotein and (c) the osteoinductive bone morphogenetic protein-4 (BMP-4) to the templates by layer-by-layer assembly. The assemblies were then incubated with hydroxyapatite nanocrystals blended with varying mass percentages of TiO2 nanoparticles and coated with alginate to form three dimensional scaffolds for potential applications in bone tissue regeneration.

Nanoformulation enhances anti-angiogenic efficacy of tunicamycin.

Nanoparticles (<100 nm) evades the immune system's clearing mechanisms long enough to reach the targeted disease tissue efficiently. We have, therefore, hypothesized that nano-formulated Tunicamycin would have a better efficacy and consequently it will be a better candidate for treating solid tumor including breast cancer in the clinic. Tunicamycin, a potent inhibitor of asparagine-linked (N-linked) protein glycosylation has been found earlier (I) inhibits angiogenesis by arresting cells in G1; (II) angiogenesis in Matrigel™ implant in nude mice; and (III) prevents the progression of a double- and a triple-negative breast tumor in athymic nude mice by inducing "ER stress" in tumor microvasculature.