29 research outputs found
Ligation of anti-cancer drugs to self-assembling ultrashort peptides by click chemistry for localized therapy
Self-assembling ultrashort peptides from aliphatic amino acids were functionalized with platinum anti-cancer drugs by click chemistry. Oxaliplatin-derived hybrid peptide hydrogels with up to 40% drug loading were tested for localized breast cancer therapy. Stably injected gels showed significant tumor growth inhibition in mice and a better tolerance compared to the free platinum drug
Advancement of Peptide Nanobiotechnology via Emerging Microfluidic Technology
Peptide nanotechnology has experienced a long and enduring development since its inception. Many different applications have been conceptualized, which depends on the functional groups present on the peptide and the physical shape/size of the peptide nanostructures. One of the most prominent nanostructures formed by peptides are nanoparticles. Until recently, however, it has been challenging to engineer peptide nanoparticles with low dispersity. An emerging and promising technique involves the utility of microfluidics to produce a solution of peptide nanoparticles with narrow dispersity. In this process, two or more streams of liquid are focused together to create conditions that are conducive towards the formation of narrowly dispersed samples of peptide nanoparticles. This makes it possible to harness peptide nanoparticles for the myriad of applications that are dependent on nanoparticle size and uniformity. In this focus review, we aim to show how microfluidics may be utilized to (1) study peptide self-assembly, which is critical to controlling nanostructure shape and size, and peptide-interface interactions, and (2) generate self-assembling peptide-based microgels for miniaturized cell cultures. These examples will illustrate how the emerging microfluidic approach promises to revolutionize the production and application of peptide nanoparticles in ever more diverse fields than before
Systematic Moiety Variations of Ultrashort Peptides Produce Profound Effects on Self-Assembly, Nanostructure Formation, Hydrogelation, and Phase Transition
Abstract Self-assembly of small biomolecules is a prevalent phenomenon that is increasingly being recognised to hold the key to building complex structures from simple monomeric units. Small peptides, in particular ultrashort peptides containing up to seven amino acids, for which our laboratory has found many biomedical applications, exhibit immense potential in this regard. For next-generation applications, more intricate control is required over the self-assembly processes. We seek to find out how subtle moiety variation of peptides can affect self-assembly and nanostructure formation. To this end, we have selected a library of 54 tripeptides, derived from systematic moiety variations from seven tripeptides. Our study reveals that subtle structural changes in the tripeptides can exert profound effects on self-assembly, nanostructure formation, hydrogelation, and even phase transition of peptide nanostructures. By comparing the X-ray crystal structures of two tripeptides, acetylated leucine-leucine-glutamic acid (Ac-LLE) and acetylated tyrosine-leucine-aspartic acid (Ac-YLD), we obtained valuable insights into the structural factors that can influence the formation of supramolecular peptide structures. We believe that our results have major implications on the understanding of the factors that affect peptide self-assembly. In addition, our findings can potentially assist current computational efforts to predict and design self-assembling peptide systems for diverse biomedical applications
Synthesis and Evaluation of Clickable Block Copolymers for Targeted Nanoparticle Drug Delivery
Polymeric nanoparticles with multifunctional capabilities,
including
surface functionalization, hold great promise to address challenges
in targeted drug delivery. Here, we describe a concise, robust synthesis
of a heterofunctional polyethylene glycol (PEG), HO-PEG-azide. This
macromer was used to synthesize polylactide (PLA)-PEG-azide, a functional
diblock copolymer. Rapid precipitation of this copolymer with a hydrophobic
cargo resulted in the generation of monodisperse nanoparticles with
azides in the surface corona. To demonstrate conjugation to these
nanoparticles, a regioselectively modified alkyne-folate was employed
as a model small molecule ligand, and the artificial protein A1 with
an alkyne moiety introduced by unnatural amino acid substitution was
selected as a model macromolecular ligand. Using the copper-catalyzed
azide–alkyne ligation reaction, both ligands exhibited good
conjugation efficiency even when low concentrations of ligands were
used
Learning CS Subjects of Professional Software Development and Team Projects
Professional Software Development (PSD) course is about the emerging profession of software engineering which involves developing, deploying, testing, and maintaining software. Currently, the Bachelor of Science with Honours in Computing Science (CS) joint degree programme of University of Glasgow (UofG) and Singapore Institute of Technology (SIT) carries out both PSD and Team Projects (TP) courses concurrently, where students are expected to apply the theory learnt from PSD to real-world projects in TP. TP is a practical project continuation from knowledge learnt in the PSD course. Both PSD and TP last two trimesters in parallel. This paper analyses the advantages and disadvantages of the current learning methods in PSD and TP. It is possible that there is still room for improvement in the current system. To further analyse the current learning system, a comparison of how the Software Engineering course is taught in other universities is also performed, from where ideas and methodology are proposed. The proposed methodology is analyzed and discussed from the suggestions or feedback of the CS students who have gone through both PSD and TP courses. The purposes are to improve the learning effectiveness of both PSD and TP courses
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De novo design and experimental characterization of ultrashort self-associating peptides.
Self-association is a common phenomenon in biology and one that can have positive and negative impacts, from the construction of the architectural cytoskeleton of cells to the formation of fibrils in amyloid diseases. Understanding the nature and mechanisms of self-association is important for modulating these systems and in creating biologically-inspired materials. Here, we present a two-stage de novo peptide design framework that can generate novel self-associating peptide systems. The first stage uses a simulated multimeric template structure as input into the optimization-based Sequence Selection to generate low potential energy sequences. The second stage is a computational validation procedure that calculates Fold Specificity and/or Approximate Association Affinity (K*association) based on metrics that we have devised for multimeric systems. This framework was applied to the design of self-associating tripeptides using the known self-associating tripeptide, Ac-IVD, as a structural template. Six computationally predicted tripeptides (Ac-LVE, Ac-YYD, Ac-LLE, Ac-YLD, Ac-MYD, Ac-VIE) were chosen for experimental validation in order to illustrate the self-association outcomes predicted by the three metrics. Self-association and electron microscopy studies revealed that Ac-LLE formed bead-like microstructures, Ac-LVE and Ac-YYD formed fibrillar aggregates, Ac-VIE and Ac-MYD formed hydrogels, and Ac-YLD crystallized under ambient conditions. An X-ray crystallographic study was carried out on a single crystal of Ac-YLD, which revealed that each molecule adopts a β-strand conformation that stack together to form parallel β-sheets. As an additional validation of the approach, the hydrogel-forming sequences of Ac-MYD and Ac-VIE were shuffled. The shuffled sequences were computationally predicted to have lower K*association values and were experimentally verified to not form hydrogels. This illustrates the robustness of the framework in predicting self-associating tripeptides. We expect that this enhanced multimeric de novo peptide design framework will find future application in creating novel self-associating peptides based on unnatural amino acids, and inhibitor peptides of detrimental self-aggregating biological proteins
Group VIII metal carbonyl cluster-boronic acid conjugates : cytotoxicity and mode of action studies
A set of metal carbonyl cluster-boronic acid conjugates of the group VIII metals (Fe, Ru, and Os) were synthesized and their antiproliferative effects measured against two breast cancer cell lines (MCF-7 and MDA-MB-231) and a noncancerous breast epithelial (MCF-10A) cell line. The cytotoxicity followed the order Ru > Os > Fe for the MDA-MB-231 cells, although the latter two exhibited similar cytotoxicity against MCF-7 and MCF-10A cells. The osmium species {Os3(CO)10(μ-H)[μ-SC6H4-p-B(OH)2]} (2) could be chemically oxidized to its hydroxy analogue [Os3(CO)10(μ-H)(μ-SC6H4-p-OH)] (2-OH), which showed comparable cytotoxicity. Mode of action studies pointed to an apoptotic pathway for cell death.Ministry of Education (MOE)Nanyang Technological UniversityPublished versionThis work was supported by Nanyang Technological University and the Ministry of Education (Research grant no. RG121/18)