A5024347530- Protein Structure and Dynamics
- Supramolecular Self-Assembly in Materials
- Chemical Synthesis and Analysis
- Antimicrobial Peptides and Activities
- RNA and protein synthesis mechanisms
- Hemoglobin structure and function
- Monoclonal and Polyclonal Antibodies Research
- Nanoplatforms for cancer theranostics
- Click Chemistry and Applications
- Biochemical and Molecular Research
- Metal complexes synthesis and properties
- Amino Acid Enzymes and Metabolism
- Antimicrobial agents and applications
- Cell Adhesion Molecules Research
- Mass Spectrometry Techniques and Applications
- Cancer-related gene regulation
- Metalloenzymes and iron-sulfur proteins
- Polydiacetylene-based materials and applications
- Advanced biosensing and bioanalysis techniques
- CRISPR and Genetic Engineering
- Retinal Development and Disorders
- Enzyme Catalysis and Immobilization
- Catalysis for Biomass Conversion
- 14-3-3 protein interactions
- Microbial Natural Products and Biosynthesis
Syracuse University
2019-2023
Nanyang Technological University
2017-2021
Advanced Centre for Treatment, Research and Education in Cancer
2014
Tata Memorial Hospital
2014
Silver compounds have been used extensively for wound healing because of their antimicrobial properties, but high concentrations silver are toxic to mammalian cells. We designed a peptide that binds and releases only small amounts this ion over time, therefore overcoming the problem toxicity. binding was achieved through incorporation an unnatural amino acid, 3′-pyridyl alanine (3′-PyA), into sequence. Upon addition ions, adopts beta-sheet secondary structure self-assembles strong hydrogel...
Abstract We have rationally designed a peptide that assembles into redox-responsive, antimicrobial metallohydrogel. The resulting self-healing material can be rapidly reduced by ascorbate under physiological conditions and demonstrates remarkable 160-fold change in hydrogel stiffness upon reduction. provide computational model of the hydrogel, explaining why position nitrogen non-natural amino acid pyridyl-alanine results drastically different gelation properties peptides with metal ions....
A short peptide, FHHF-11, was designed to change stiffness as a function of pH due changing degree protonation histidines. As changes in the physiologically relevant range, G' measured at 0 Pa (pH 6) and 50,000 8). This peptide-based hydrogel is antimicrobial cytocompatible with skin cells (fibroblasts). It demonstrated that incorporation unnatural AzAla tryptophan analog residue improves properties hydrogel. The material developed can have practical application be paradigm shift approach...
High‐temperature requirement protease A 2 (HtrA2), a multitasking serine that is involved in critical biological functions and pathogenicity, such as apoptosis cancer, potent therapeutic target. It established the C ‐terminal post‐synaptic density protein, D rosophila disc large tumor suppressor, zonula occludens‐1 protein ( PDZ ) domain of H trA2 plays pivotal role allosteric modulation, substrate binding activation, commonly reported other members this family. Interestingly, exhibits an...
The structure and function of naturally occurring proteins are governed by a large number amino acids (≥100). design miniature with desired structures functions not only substantiates our knowledge about but can also contribute to the development novel applications. Excellent progress has been made towards helical diverse functions. However, functional β-sheet remains challenging. Herein, we describe construction characterization four-stranded miniproteins up 19 that bind heme inside...
Antimicrobial peptides (AMPs) present a promising scaffold for the development of potent antimicrobial agents. Substitution tryptophan by non-natural amino acid Azulenyl-Alanine (AzAla) would allow studying mechanism action AMPs using unique properties this acid, such as ability to be excited separately from in multi-Trp and environmental insensitivity. In work, we investigate effect Trp→AzAla substitution peptide buCATHL4B (contains three Trp side chains). We found that bactericidal...
Structures and functions of designed multi-stranded heme binding β-sheet peptides carrying out peroxidase activity electron transfer in membrane.
Abstract Nature has primarily exploited helical proteins, over β-sheets, for heme/multi-heme coordination. Understating of heme–protein structures motivated the design heme proteins utilizing coiled-coil structure. By contrast, de novo designed β-sheet are less successful. However, designing with discretely folded encoding specific functions would have great potential development new synthetic molecules e.g. enzymes, inhibitors. Here we report and characterization multi-heme binding four-,...
Metalloenzymes often utilize radicals in order to facilitate chemical reactions. Recently, DeGrado and co-workers have discovered that model proteins can efficiently stabilize semiquinone radical anion produced by oxidation of 3,5-di-tert-butylcatechol (DTBC) the presence two zinc ions. Here, we show number nature metal ions relatively minor effect on stabilization proteins, with a single ion being sufficient for stabilization. The is stabilized both ion, hydrophobic sequestration,...
The structure and function of naturally occurring proteins are governed by a large number amino acids (≥100). design miniature with desired structures functions not only substantiates our knowledge about but can also contribute to the development novel applications. Excellent progress has been made towards helical diverse functions. However, functional β-sheet remains challenging. Herein, we describe construction characterization four-stranded miniproteins up 19 that bind heme inside...
Abstract Minimalist enzymes designed to catalyze model reactions provide useful starting points for creating catalysts practically important chemical transformations. We have shown that Kemp eliminases of the AlleyCat family facilitate conversion leflunomide (an immunosuppressor pro‐drug) its active form teriflunomide with outstanding rate enhancement (nearly four orders magnitude) and catalytic proficiency (more than seven without any additional optimization. This remarkable activity is...
Abstract Directed evolution can rapidly achieve dramatic improvements in the properties of a protein or bestow entirely new functions on it. We have discovered strong correlation between probability finding productive mutation at particular position and chemical shift perturbation Nuclear Magnetic Resonance spectra upon addition an inhibitor for reaction it promotes. In proof-of-concept study we converted myoglobin, non-enzymatic protein, into most active Kemp eliminase reported to date...
Abstract The front cover artwork for Issue 05/2019 is provided by the Korendoych and Makhlynets Labs at Syracuse University (USA) in collaboration with VIB Centre Structural Biology (Belgium), College of Charleston Kyiv National (Ukraine). image shows AlleyCat2, a minimalist allosterically regulated Kemp eliminase, efficiently promoting ring opening leflunomide, an immunosuppresant. Small libraries designed catalysts provide fertile ground discovering new reactivities. See Communication...
Directed evolution has emerged as a powerful tool for improving protein properties and imparting completely new functionalities onto existing proteins. Several computational methods have been successful in predicting potential hotspots directed evolution. However, they rely heavily on prior structural and/or functional information. To address these fundamental limitations, we focused Nuclear Magnetic Resonance (NMR) to rapidly evolve enzymes without characterization. AlleyCat,...