The Mitochondria-to-Cytosol HO Gradient Is Caused by Peroxiredoxin-Dependent Cytosolic Scavenging.

Fluorescent protein-based reporters used to measure intracellular HO were developed to overcome the limitations of small permeable dyes. The two major families of genetically encoded redox reporters are the reduction-oxidation sensitive green fluorescent protein (roGFP)-based proteins fused to peroxiredoxins and HyPer and derivatives. We have used the most sensitive probes of each family, roGFP2-Tpx1.

HO and Engrailed 2 paracrine activity synergize to shape the zebrafish optic tectum.

Although a physiological role for redox signaling is now clearly established, the processes sensitive to redox signaling remains to be identified. Ratiometric probes selective for HO have revealed its complex spatiotemporal dynamics during neural development and adult regeneration and perturbations of HO levels disturb cell plasticity and morphogenesis. Here we ask whether endogenous HO could participate in the patterning of the embryo.

Ultrasensitive Genetically Encoded Indicator for Hydrogen Peroxide Identifies Roles for the Oxidant in Cell Migration and Mitochondrial Function.

Hydrogen peroxide (HO) is a key redox intermediate generated within cells. Existing probes for HO have not solved the problem of detection of the ultra-low concentrations of the oxidant: these reporters are not sensitive enough, or pH-dependent, or insufficiently bright, or not functional in mammalian cells, or have poor dynamic range. Here we present HyPer7, the first bright, pH-stable, ultrafast, and ultrasensitive ratiometric HO probe.

Design of a highly potent inhibitory peptide acting as a competitive inhibitor of HMG-CoA reductase.

This study presents a design of a highly potent and competitive inhibitory peptide for 3-hydroxy-3-methylglutaryl CoA reductase (HMGR). HMGR is the major regulatory enzyme of cholesterol biosynthesis and the target enzyme of many investigations aimed at lowering the rate of cholesterol biosynthesis. In previous studies, the two hypocholesterolemic peptides (LPYP and IAVPGEVA) were isolated and identified from soy protein.

Peptide fragmentation as an approach in modeling of an active peptide and designing a competitive inhibitory peptide for HMG-CoA reductase.

This study presents a simple method to design an active peptide based on a description of the structural preferences of peptide via its peptide fragments. In a previous design, while searching for lead peptide candidates, the efficacy of a design approach that was based on the use of a cyclic peptide as a model of linear analog was demonstrated. Analysis of the conformational behavior of the peptide models showed that an analogical approach could be applied in order to assess the conformational space that was occupied by a peptide by using peptide fragments.

Modeling an active conformation for linear peptides and design of a competitive inhibitor for HMG-CoA reductase.

This study presents an approach that can be used to search for lead peptide candidates, including unconstrained structures in a recognized sequence. This approach was performed using the design of a competitive inhibitor for 3-hydroxy-3-methylglutaryl CoA reductase (HMGR). In a previous design for constrained peptides, a head-to-tail cyclic structure of peptide was used as a model of linear analog in searches for lead peptides with a structure close to an active conformation.

Binding effect and design of a competitive inhibitory peptide for HMG-CoA reductase through modeling of an active peptide backbone.

This study presents an application of two approaches in the design of constrained and unconstrained peptides in an investigation of the peptide binding effect for HMG-CoA reductase (HMGR). In previous works, hypocholesterolemic peptides isolated from soybean were determined as competitive inhibitory peptides for HMGR. Based on the modeling of an active peptide backbone in the active site of HMGR, two peptide libraries for constrained and unconstrained peptides were designed using different amino acids varying in hydrophobicity and electronic properties.

Recognized sequence and conformation in design of linear peptides as a competitive inhibitor for HMG-CoA reductase.

This study is an attempt to develop a simple search method for lead peptide candidates, which include constrained structures in a recognized sequence, using the design of a competitive inhibitor for HMG-CoA reductase (HMGR). A structure-functional analysis of previously synthesized peptides proposes that a competitive inhibitory peptide can be designed by maintaining bioactive conformation in a recognized sequence. A conformational aspect of the structure-based approach was applied to the peptide design.

Peptide design of a competitive inhibitor for HMG-CoA reductase based on statin structure.

This study investigates a proposed design of a peptide sequence that is based on a bioactive conformation of statins that act as the competitive inhibitors of HMG-CoA for HMGR. To bridge these heterogeneous organic compounds, a conformational aspect relating to an analysis of the flexibility of the peptide molecules and their occupied volumes was applied to the peptide design. The design criterion was formulated in terms of a proximity parameter (Pr), reflecting the probability of an active peptide conformation to approximate the statin.