M. Reza Ghadiri

Bio: M. Reza Ghadiri is an academic researcher from Scripps Research Institute. The author has contributed to research in topics: Cyclic peptide & Peptide. The author has an hindex of 65, co-authored 126 publications receiving 17011 citations. Previous affiliations of M. Reza Ghadiri include Salk Institute for Biological Studies & University of California, San Diego.

Self-assembling organic nanotubes based on a cyclic peptide architecture

Abstract: Hollow tubular structures of molecular dimensions may offer a variety of applications in chemistry, biochemistry and materials science. Concentric carbon nanotubes have attracted a great deal of attention, while the three-dimensional tubular pore structures of molecular sieves have long been exploited industrially. Nanoscale tubes based on organic materials have also been reported previously. Here we report the design, synthesis and characterization of a new class of organic nanotubes based on rationally designed cyclic polypeptides. When protonated, these compounds crystallize into tubular structures hundreds of nanometres long, with internal diameters of 7-8 A. Support for the proposed tubular structures is provided by electron microscopy, electron diffraction, Fourier-transform infrared spectroscopy and molecular modelling. These tubes are open-ended, with uniform shape and internal diameter. We anticipate that they may have possible applications in inclusion chemistry, catalysis, molecular electronics and molecular separation technology.

A Porous Silicon-Based Optical Interferometric Biosensor

Abstract: A biosensor has been developed based on induced wavelength shifts in the Fabry-Perot fringes in the visible-light reflection spectrum of appropriately derivatized thin films of porous silicon semiconductors. Binding of molecules induced changes in the refractive index of the porous silicon. The validity and sensitivity of the system are demonstrated for small organic molecules (biotin and digoxigenin), 16-nucleotide DNA oligomers, and proteins (streptavidin and antibodies) at pico- and femtomolar analyte concentrations. The sensor is also highly effective for detecting single and multilayered molecular assemblies.

Self-Assembling Organic Nanotubes

Abstract: Hollow tubular structures of molecular dimensions perform diverse biological functions in nature. Examples include scaffolding and packaging roles played by cytoskeletal microtubules and viral coat proteins, respectively, as well as the chemical transport and screening activities of membrane channels. In the preparation of such tubular assemblies, biological systems make extensive use of self-assembling and self-organizing strategies. Owing to numerous potential applications in areas such as chemistry, biology, and materials science considerable effort has recently been devoted to preparation of artificial nanotubular structures. This article reviews design principles and the preparation of synthetic organic nanotubes, with special emphasis on noncovalent processes such as self-assembly and self-organization.

Antibacterial agents based on the cyclic D,L-alpha-peptide architecture

Abstract: The rapid emergence of bacterial infections that are resistant to many drugs underscores the need for new therapeutic agents. Here we report that six- and eight-residue cyclic d,l-alpha-peptides act preferentially on Gram-positive and/or Gram-negative bacterial membranes compared to mammalian cells, increase membrane permeability, collapse transmembrane ion potentials, and cause rapid cell death. The effectiveness of this class of materials as selective antibacterial agents is highlighted by the high efficacy observed against lethal methicillin-resistant Staphylococcus aureus infections in mice. Cyclic d,l-alpha-peptides are proteolytically stable, easy to synthesize, and can be derived from a potentially vast membrane-active sequence space. The unique abiotic structure of the cyclic peptides and their quick bactericidal action may also contribute to limit temporal acquirement of drug resistant bacteria. The low molecular weight d,l-alpha-peptides offer an attractive complement to the current arsenal of naturally derived antibiotics, and hold considerable potential in combating a variety of existing and emerging infectious diseases.

Self-Assembling Peptide Nanotubes

Abstract: The general design criteria and synthesis of four new peptide-based solid-state tubular array structures are described. Peptide nanotubes, which are extended tubular β-sheet-like structures, are constructed by the self-assembly of flat, ring-shaped peptide subunits made up of alternating d- and l-amino acid residues. Peptide self-assembly is directed by the formation of an extensive network of intersubunit hydrogen bonds. In the crystal structures, nanotubes are stabilized by intertubular hydrophobic packing interactions. Peptide nanotubes exhibit good mechanical and thermal stabilities in water and are stable for long periods of times in most common organic solvents including DMF and DMSO. The remarkable stability of peptide nanotubes can be attributed to the highly cooperative nature of the noncovalent interactions throughout the crystal lattice. Nanotube structures were characterized by cryoelectron microscopy, electron diffraction, Fourier-transform infrared spectroscopy, and crystal structure modelin...

Phd by thesis

Abstract: Deposits of clastic carbonate-dominated (calciclastic) sedimentary slope systems in the rock record have been identified mostly as linearly-consistent carbonate apron deposits, even though most ancient clastic carbonate slope deposits fit the submarine fan systems better. Calciclastic submarine fans are consequently rarely described and are poorly understood. Subsequently, very little is known especially in mud-dominated calciclastic submarine fan systems. Presented in this study are a sedimentological core and petrographic characterisation of samples from eleven boreholes from the Lower Carboniferous of Bowland Basin (Northwest England) that reveals a >250 m thick calciturbidite complex deposited in a calciclastic submarine fan setting. Seven facies are recognised from core and thin section characterisation and are grouped into three carbonate turbidite sequences. They include: 1) Calciturbidites, comprising mostly of highto low-density, wavy-laminated bioclast-rich facies; 2) low-density densite mudstones which are characterised by planar laminated and unlaminated muddominated facies; and 3) Calcidebrites which are muddy or hyper-concentrated debrisflow deposits occurring as poorly-sorted, chaotic, mud-supported floatstones. These

Antimicrobial peptides of multicellular organisms

Abstract: Multicellular organisms live, by and large, harmoniously with microbes. The cornea of the eye of an animal is almost always free of signs of infection. The insect flourishes without lymphocytes or antibodies. A plant seed germinates successfully in the midst of soil microbes. How is this accomplished? Both animals and plants possess potent, broad-spectrum antimicrobial peptides, which they use to fend off a wide range of microbes, including bacteria, fungi, viruses and protozoa. What sorts of molecules are they? How are they employed by animals in their defence? As our need for new antibiotics becomes more pressing, could we design anti-infective drugs based on the design principles these molecules teach us?

Next-generation DNA sequencing.

Abstract: DNA sequence represents a single format onto which a broad range of biological phenomena can be projected for high-throughput data collection. Over the past three years, massively parallel DNA sequencing platforms have become widely available, reducing the cost of DNA sequencing by over two orders of magnitude, and democratizing the field by putting the sequencing capacity of a major genome center in the hands of individual investigators. These new technologies are rapidly evolving, and near-term challenges include the development of robust protocols for generating sequencing libraries, building effective new approaches to data-analysis, and often a rethinking of experimental design. Next-generation DNA sequencing has the potential to dramatically accelerate biological and biomedical research, by enabling the comprehensive analysis of genomes, transcriptomes and interactomes to become inexpensive, routine and widespread, rather than requiring significant production-scale efforts.

Cu-catalyzed azide-alkyne cycloaddition.

Abstract: The Huisgen 1,3-dipolar cycloaddition reaction of organic azides and alkynes has gained considerable attention in recent years due to the introduction in 2001 of Cu(1) catalysis by Tornoe and Meldal, leading to a major improvement in both rate and regioselectivity of the reaction, as realized independently by the Meldal and the Sharpless laboratories. The great success of the Cu(1) catalyzed reaction is rooted in the fact that it is a virtually quantitative, very robust, insensitive, general, and orthogonal ligation reaction, suitable for even biomolecular ligation and in vivo tagging or as a polymerization reaction for synthesis of long linear polymers. The triazole formed is essentially chemically inert to reactive conditions, e.g. oxidation, reduction, and hydrolysis, and has an intermediate polarity with a dipolar moment of ∼5 D. The basis for the unique properties and rate enhancement for triazole formation under Cu(1) catalysis should be found in the high ∆G of the reaction in combination with the low character of polarity of the dipole of the noncatalyzed thermal reaction, which leads to a considerable activation barrier. In order to understand the reaction in detail, it therefore seems important to spend a moment to consider the structural and mechanistic aspects of the catalysis. The reaction is quite insensitive to reaction conditions as long as Cu(1) is present and may be performed in an aqueous or organic environment both in solution and on solid support.

Real-Time DNA Sequencing from Single Polymerase Molecules

Abstract: We present single-molecule, real-time sequencing data obtained from a DNA polymerase performing uninterrupted template-directed synthesis using four distinguishable fluorescently labeled deoxyribonucleoside triphosphates (dNTPs). We detected the temporal order of their enzymatic incorporation into a growing DNA strand with zero-mode waveguide nanostructure arrays, which provide optical observation volume confinement and enable parallel, simultaneous detection of thousands of single-molecule sequencing reactions. Conjugation of fluorophores to the terminal phosphate moiety of the dNTPs allows continuous observation of DNA synthesis over thousands of bases without steric hindrance. The data report directly on polymerase dynamics, revealing distinct polymerization states and pause sites corresponding to DNA secondary structure. Sequence data were aligned with the known reference sequence to assay biophysical parameters of polymerization for each template position. Consensus sequences were generated from the single-molecule reads at 15-fold coverage, showing a median accuracy of 99.3%, with no systematic error beyond fluorophore-dependent error rates.