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Current Opinion in Chemical Biology

Xinyi Y Zhou, Zhi Wei Tay, Prashant Chandrasekharan, Elaine Y Yu, Daniel W Hensley, Ryan Orendorff, Kenneth E Jeffris, David Mai, Bo Zheng, Patrick W Goodwill, Steven M Conolly
Magnetic particle imaging (MPI) is an emerging ionizing radiation-free biomedical tracer imaging technique that directly images the intense magnetization of superparamagnetic iron oxide nanoparticles (SPIOs). MPI offers ideal image contrast because MPI shows zero signal from background tissues. Moreover, there is zero attenuation of the signal with depth in tissue, allowing for imaging deep inside the body quantitatively at any location. Recent work has demonstrated the potential of MPI for robust, sensitive vascular imaging and cell tracking with high contrast and dose-limited sensitivity comparable to nuclear medicine...
May 10, 2018: Current Opinion in Chemical Biology
Jacques Lux, A Dean Sherry
The gadolinium-based contrast agents widely used in diagnostic MRI exams for 30 years are all small molecule agents that distribute into all extracellular spaces in tissues without providing any specific biological information. Although many 'responsive agent' designs have been presented over the past 20 years or so, none have found use in clinical diagnostic medicine at this point. This review summarizes some recent approaches taken to enhance the sensitivity of such gadolinium-based agents, to target them to specific tissue components, and to create new systems for monitoring specific biological processes...
May 8, 2018: Current Opinion in Chemical Biology
Pongphak Chidchob, Hanadi F Sleiman
DNA is a powerful guiding molecule to achieve the precise construction of arbitrary structures and high-resolution organization of functional materials. The combination of sequence programmability, rigidity and highly specific molecular recognition in this molecule has resulted in a wide range of exquisitely designed DNA frameworks. To date, the impressive potential of DNA nanomaterials has been demonstrated from fundamental research to technological advancements in materials science and biomedicine. This review presents a summary of some of the most recent developments in structural DNA nanotechnology regarding new assembly approaches and efforts in translating DNA nanomaterials into practical use...
May 8, 2018: Current Opinion in Chemical Biology
Daniel Schindler, Junbiao Dai, Yizhi Cai
Since the first synthetic gene was synthesized in 1970s, the efficiency and the capacity of made-to-order DNA sequence synthesis has increased by several orders of magnitude. Advances in DNA synthesis and assembly over the past years has resulted in a steep drop in price for custom made DNA. Similar effects were observed in DNA sequencing technologies which underpin DNA-reading projects. Today, synthetic DNA sequences with more than 10000bps and turn-around times of a few weeks are commercially available. This enables researchers to perform large-scale projects to write synthetic chromosomes and characterize their functionalities in vivo...
May 8, 2018: Current Opinion in Chemical Biology
Jun Liu, Rujin Cheng, Sharon Rozovsky
The versatile chemistry of the genetically encoded amino acid selenocysteine (Sec) is employed in Nature to expand the reactivity of enzymes. In addition to, its role in biology, Sec is used in protein engineering to modify folding, stability, and reactivity of proteins, to introduce conjugations and to facilitate reactions. However, due to limitations related to Sec's insertion mechanism in Nature, much of the production of Sec containing peptides and proteins relies on synthesis and semisynthesis. Here, we review recent advances that have enabled the assembly of complicated selenoproteins, including novel uses of protecting groups for solid phase peptide synthesis, rapid selenoester driven chemical ligations and versatile expressed protein ligations...
April 30, 2018: Current Opinion in Chemical Biology
Alonso Pardo-Vargas, Martina Delbianco, Peter H Seeberger
Access to complex carbohydrates remains a limiting factor for the development of the glycosciences. Automated glycan assembly (AGA) has accelerated and simplified the synthetic process and, with the first commercially available instrument and building blocks, glycan synthesis can now be practiced by any chemist. All classes of glycans, including sulfated or sialylated carbohydrates and polysaccharides as long as 50mers are now accessible owing to optimized reaction conditions and new methodologies. These synthetic glycans have helped to understand many biological functions and to advance diagnostic and vaccine development...
April 28, 2018: Current Opinion in Chemical Biology
David M Perrin
To meet the long-standing challenge of a one-step, last-stage aqueous radiofluorination method for labeling large, water-soluble molecules such as peptides, we sought a mild aqueous fluorination reaction that uses organoboron compositions, which are readily fluorinated in mild aqueous acid to give 18 F-labeled organotrifluoroborates. This robust reaction now provides new 18 F-labeled radioprosthetic groups that can be pre-conjugated to peptides and other polar molecules, and then labeled with aqueous no-carrier-added (NCA) [18 F]fluoride ion in a single step...
April 20, 2018: Current Opinion in Chemical Biology
Lara R Malins
Transition-metal catalysis has unlocked new paradigms for the late-stage modification and cyclization of peptides by harnessing the innate reactivity of proteinogenic amino acids. The field is rapidly evolving, with recent advances encompassing three fundamental areas-heteroatom couplings, decarboxylative cross-couplings, and C-H functionalizations-which have markedly extended the scope of conventional peptide modification and bioconjugation strategies. The advances outlined herein facilitate access to high-value peptide targets with promising applications in materials science and drug discovery...
April 12, 2018: Current Opinion in Chemical Biology
Bingjia Yan, Weiwei Shi, Linzhi Ye, Lei Liu
Native chemical ligation (NCL) has become one of the most important methods in chemical syntheses of proteins. Recently, in order to expand its scope, considerable effort has been devoted to tuning the C-terminal acyl donor thioesters used in NCL. This article reviews the recent advances in the design of C-terminal acyl donors, their precursors and surrogates, and highlights some noteworthy progress that may lead the future direction of protein chemical synthesis.
April 11, 2018: Current Opinion in Chemical Biology
Lucas A Lane, Ruiyang Xue, Shuming Nie
Two clear windows in the near-infrared (NIR) spectrum are of considerable current interest for in vivo molecular imaging and spectroscopic detection. The main rationale is that near-infrared light can penetrate biological tissues such as skin and blood more efficiently than visible light because these tissues scatter and absorb less light at longer wavelengths. The first clear window, defined as light wavelengths between 650nm and 950nm, has been shown to be far superior for in vivo and intraoperative optical imaging than visible light...
April 6, 2018: Current Opinion in Chemical Biology
Aimen Zlitni, Sanjiv S Gambhir
Ultrasound (US) imaging is a safe, sensitive and affordable imaging modality with a wide usage in the clinic. US signal can be further enhanced by using echogenic contrast agents (UCAs) which amplify the US signal. Developments in UCAs which are targeted to sites of disease allow the use of US imaging to provide molecular information. Unfortunately, traditional UCAs are too large to leave the vascular space limiting the application of molecular US to intravascular markers. In this mini review, we highlight the most recent reports on the application of molecular US imaging in the clinic and summarize the latest nanoparticle platforms used to develop nUCAs...
April 6, 2018: Current Opinion in Chemical Biology
Junjie Yao, Lihong V Wang
By acoustically detecting the optical absorption contrast, photoacoustic (PA) tomography (PAT) has broken the penetration limits of traditional high-resolution optical imaging. Through spectroscopic analysis of the target's optical absorption, PAT can identify a wealth of endogenous and exogenous molecules and thus is inherently capable of molecular imaging with high sensitivity. PAT's molecular sensitivity is uniquely accompanied by non-ionizing radiation, high spatial resolution, and deep penetration in biological tissues, which other optical imaging modalities cannot achieve yet...
April 6, 2018: Current Opinion in Chemical Biology
Kenzo Yamatsugu, Shigehiro A Kawashima, Motomu Kanai
In recent years, our knowledge of the epigenetic functions regulated by post-translational modifications (PTMs) of histones, and their role in various diseases, has expanded rapidly, opening the way to novel therapeutic strategies that treat epigenetic abnormalities. Many of the current approaches have been focusing on the chemical inhibition of histone-modifying enzymes to modulate histone PTM states for attaining therapeutic effects. However, recent developments in chemistry and molecular biology have contributed to the emergence of new methods that introduce histone PTMs entirely through artificial means, without reliance on endogenous enzymes...
April 6, 2018: Current Opinion in Chemical Biology
Iain A Stepek, Jeffrey W Bode
The concept of synthetic fermentation is to 'grow' complex organic molecules in a controlled and predictable manner by combining small molecule building blocks in water-without the need for reagents, enzymes, or organisms. This approach mimics the production of small mixtures of structurally related natural products by living organisms, particularly microbes, under conditions compatible with direct screening of the cultures for biological activity. This review discusses the development and implementation of this concept, its use for the discovery of protease inhibitors, its basis as a chemistry outreach program allowing non-specialists to make and discover new antibiotics, and highlights of related approaches...
April 5, 2018: Current Opinion in Chemical Biology
Stephen Bh Kent
A racemic protein mixture can be used to form centrosymmetric crystals for structure determination by X-ray diffraction. Both the unnatural d-protein and the corresponding natural l-protein are made by total chemical synthesis based on native chemical ligation-chemoselective condensation of unprotected synthetic peptide segments. Racemic protein crystallography is important for structure determination of the many natural protein molecules that are refractory to crystallization. Racemic mixtures facilitate the crystallization of recalcitrant proteins, and give diffraction-quality crystals...
April 4, 2018: Current Opinion in Chemical Biology
Alexander-Thomas Hauser, Dina Robaa, Manfred Jung
DNA and histone methylation belong to the key regulatory components in the epigenetic machinery, and dysregulations of these processes have been associated with various human diseases. Small molecule modulators of these epigenetic targets are highly valuable both as chemical probes to study the biological roles of the target proteins, and as potential therapeutics. Indeed, recent years have seen the discovery of chemical modulators of several epigenetic targets, some of which are already marketed drugs or undergoing clinical trials...
March 23, 2018: Current Opinion in Chemical Biology
Philip S Low, Sunil Singhal, Madduri Srinivasarao
Thousands of patients die each year from residual cancer that remains following cytoreductive surgery. Use of tumor-targeted fluorescent dyes (TTFDs) to illuminate undetected malignant tissue and thereby facilitate its surgical resection shows promise for reducing morbidity and mortality associated with unresected malignant disease. TTFDs can also improve i) detection of recurrent malignant lesions, ii) differentiation of normal from malignant lymph nodes, iii) accurate staging of cancer patients, iv) detection of tumors during robotic/endoscopic surgery (where tumor palpation is no longer possible), and v) preservation of healthy tissue during resection of cancer tissue...
March 23, 2018: Current Opinion in Chemical Biology
George J Lu, Arash Farhadi, Arnab Mukherjee, Mikhail G Shapiro
A long-standing goal of molecular imaging is to visualize cellular function within the context of living animals, necessitating the development of reporter genes compatible with deeply penetrant imaging modalities such as ultrasound and magnetic resonance imaging (MRI). Until recently, no reporter genes for ultrasound were available, and most genetically encoded reporters for MRI were limited by metal availability or relatively low sensitivity. Here we review how these limitations are being addressed by recently introduced reporter genes based on air-filled and water-transporting biomolecules...
March 14, 2018: Current Opinion in Chemical Biology
Richard R Meehan, John P Thomson, Antonio Lentini, Colm E Nestor, Sari Pennings
Recent progress in interpreting comprehensive genetic and epigenetic profiles for human cellular states has contributed new insights into the developmental origins of disease, elucidated novel signalling pathways and enhanced drug discovery programs. A similar comprehensive approach to decoding the epigenetic readouts from chemical challenges in vivo would yield new paradigms for monitoring and assessing environmental exposure in model systems and humans.
March 2, 2018: Current Opinion in Chemical Biology
Simon Nadal, Ritu Raj, Shabaz Mohammed, Benjamin G Davis
Chromatin is the physiological template of genetic information in all eukaryotic cells, a highly organised complex of DNA and histone proteins central in regulating gene expression and genome organisation. A multitude of histone post-translational modifications (PTMs) have been discovered, providing a glance into the complex interplay of these epigenetic marks in cellular processes. In the last decade, synthetic and chemical biology techniques have emerged to study these modifications, including genetic code expansion, histone semisynthesis and post-translational chemical mutagenesis...
February 28, 2018: Current Opinion in Chemical Biology
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