Recent, non-classical, approaches to antibody lysine modification
Publication date: Available online 27 September 2018Source: Drug Discovery Today: TechnologiesAuthor(s): Guilhem Chaubet, Fabien Thoreau, Alain WagnerThis review will discuss recent development in the bioconjugation of lysine residues on antibodies. As several chemoselective reagents have already been developed for modifying amine groups, recent strategies now tend to aim at being site-specific. Four general methods have been listed: kinetically controlled, template-directed or enzymatic strategies as well as the use of chemically programmed antibodies.Graphical abstract (Source: Drug Discovery Today: Technologies)
Source: Drug Discovery Today: Technologies - October 5, 2018 Category: Drugs & Pharmacology Source Type: research
Homologation of Ugi and Passerini reactions using ynamides
Publication date: Available online 20 September 2018Source: Drug Discovery Today: TechnologiesAuthor(s): Bo Huang, Sunliang CuiBeing important biological and pharmacological units, β-amino amides and β-acyloxy amides have a privileged position in both academia and industry. Developing a methods to prepare them has gained attention. Ynamides, which possess dual nucleophilic and electrophilic properties, are similar to isonitriles. In this review, usage of ynamides in the single reactant replacement approach of Ugi and Passerini reactions to develop two new multicomponent reactions to get various β-amino amides and β-acy...
Source: Drug Discovery Today: Technologies - September 20, 2018 Category: Drugs & Pharmacology Source Type: research
Borylated reagents for multicomponent reactions
Publication date: Available online 10 September 2018Source: Drug Discovery Today: TechnologiesAuthor(s): Joanne Tan, Andrei K. YudinOver the past two decades, there has been an increasing interest in the therapeutic potential of organoboron reagents due to the discovery of bortezomib (Velcade). This has motivated synthetic chemists to develop novel routes for the preparation of heteroatom-rich boron-containing molecules (BCMs). In particular, the development of borylated building blocks has provided facile access to difficult-to-access heteroatom-rich BCMs. In this review, we will discuss the methods used to prepare boron-...
Source: Drug Discovery Today: Technologies - September 11, 2018 Category: Drugs & Pharmacology Source Type: research
Crispr/Cas9 homologous recombination (HR)
Publication date: August 2018Source: Drug Discovery Today: Technologies, Volume 28Author(s): Milena Bellin (Source: Drug Discovery Today: Technologies)
Source: Drug Discovery Today: Technologies - September 9, 2018 Category: Drugs & Pharmacology Source Type: research
Recent advances of the Povarov reaction in medicinal chemistry
Publication date: Available online 28 August 2018Source: Drug Discovery Today: TechnologiesAuthor(s): Ouldouz Ghashghaei, Carme Masdeu, Concepción Alonso, Francisco Palacios, Rodolfo LavillaThe Povarov multicomponent reaction consists on the condensation of an aniline, an aldehyde, and an activated olefin to generate a tetrahydroquinoline adduct with 3 diversity points. Hereby, we report the main features of this transformation and its uses in medicinal chemistry. Relevant examples of the impact of Povarov adducts in different therapeutic areas are provided.Graphical abstract (Source: Drug Discovery Today: Technologies)
Source: Drug Discovery Today: Technologies - August 29, 2018 Category: Drugs & Pharmacology Source Type: research
Gold-catalyzed post-MCR transformations towards complex (poly)heterocycles
Publication date: Available online 28 August 2018Source: Drug Discovery Today: TechnologiesAuthor(s): Upendra K. Sharma, Guilong Tian, Leonid G. Voskressensky, Erik V. Van der EyckenPost multicomponent reaction (MCR) transformations are one of the most successful methods leading to high structural diversity and molecular complexity. A well-known MCR, the Ugi reaction typically affords a linear peptide backbone, enabling post-Ugi transformations as an elegant solution to rigidify the Ugi adduct into more drug-like species. Not surprisingly, the development of such transformations leading to new structural frameworks has exp...
Source: Drug Discovery Today: Technologies - August 29, 2018 Category: Drugs & Pharmacology Source Type: research
CRISPR/Cas9 genome engineering in hematopoietic cells
Publication date: Available online 25 August 2018Source: Drug Discovery Today: TechnologiesAuthor(s): Duran Sürün, Harald von Melchner, Frank SchnütgenThe development of genome editing tools capable of modifying specific genomic sequences with unprecedented accuracy has opened up a wide range of new possibilities in targeted gene manipulation. In particular, the CRISPR/Cas9 system, a repurposed prokaryotic adaptive immune system, has been widely adopted because of its unmatched simplicity and flexibility.In this review we discuss achievements and current limitations of CRISPR/Cas9 genome editing in hematopoietic cells w...
Source: Drug Discovery Today: Technologies - August 26, 2018 Category: Drugs & Pharmacology Source Type: research
Physicochemical characterisation in drug discovery
Publication date: July 2018Source: Drug Discovery Today: Technologies, Volume 27Author(s): György T. Balogh (Source: Drug Discovery Today: Technologies)
Source: Drug Discovery Today: Technologies - August 11, 2018 Category: Drugs & Pharmacology Source Type: research
CRISPR/Cas9 disease models in zebrafish and Xenopus: The genetic renaissance of fish and frogs
Publication date: Available online 31 July 2018Source: Drug Discovery Today: TechnologiesAuthor(s): Thomas Naert, Kris VleminckxThe speed by which clinical genomics is currently identifying novel potentially pathogenic variants is outperforming the speed by which these can be functionally (genotype–phenotype) annotated in animal disease models. However, over the past few years the emergence of CRISPR/Cas9 as a straight-forward genome editing technology has revolutionized disease modeling in vertebrate non-mammalian model organisms such as zebrafish, medaka and Xenopus. It is now finally possible, by CRISPR/Cas9, to rapid...
Source: Drug Discovery Today: Technologies - August 1, 2018 Category: Drugs & Pharmacology Source Type: research
Minireview: Addressing the retro-Michael instability of maleimide bioconjugates
Publication date: Available online 29 July 2018Source: Drug Discovery Today: TechnologiesAuthor(s): Peter A. Szijj, Calise Bahou, Vijay ChudasamaBioconjugation, the modification of biological macromolecules such as proteins, is an up and coming area in the field of chemical biology. Antibody-drug conjugates (ADCs), combining the antigen-selectivity of natural antibodies with the cytotoxic potency of small molecule drugs, are a powerful therapeutic technology. Four such constructs are currently on the market for cancer therapy. However, the conjugation methodology employed in these therapeutics is far from ideal. Herein we ...
Source: Drug Discovery Today: Technologies - July 30, 2018 Category: Drugs & Pharmacology Source Type: research
Matrix systems for oral drug delivery: Formulations and drug release
Publication date: Available online 23 July 2018Source: Drug Discovery Today: TechnologiesAuthor(s): Gábor Vasvári, József Kalmár, Péter Veres, Miklós Vecsernyés, Ildikó Bácskay, Pálma Fehér, Zoltán Ujhelyi, Ádám Haimhoffer, Ágnes Rusznyák, Ferenc Fenyvesi, Judit VáradiIn this current article matrix formulations for oral drug delivery are reviewed. Conventional dosage forms and novel applications such as 3D printed matrices and aerogel matrices are discussed. Beside characterization, excipients and matrix forming agents are also enlisted and classified. The incorporated drug could exist in crystalline or in...
Source: Drug Discovery Today: Technologies - July 24, 2018 Category: Drugs & Pharmacology Source Type: research
Petasis three-component reactions for the synthesis of diverse heterocyclic scaffolds
Publication date: Available online 17 July 2018Source: Drug Discovery Today: TechnologiesAuthor(s): Peng Wu, Thomas E. NielsenThe Petasis three-component reaction (PR) of hydroxy aldehydes, amines and boronic acids is an important multi-component reaction for the synthesis of structurally diverse scaffolds and biologically interesting small molecules. The reaction has been significantly explored in the past decade, and many new variants have emerged, such as asymmetric, traceless and four-component approaches. The excellent stereoselectivity, high yield and broad functional group tolerance altogether make this reaction ide...
Source: Drug Discovery Today: Technologies - July 18, 2018 Category: Drugs & Pharmacology Source Type: research
Macrocycles: MCR synthesis and applications in drug discovery
Publication date: Available online 12 July 2018Source: Drug Discovery Today: TechnologiesAuthor(s): Eman M.M. Abdelraheem, Shabnam Shaabani, Alexander DömlingMacrocycles are an emerging and largely underexploited part of chemical space where potential drugs for difficult genomic targets can be discovered. Macrocycles can have advantages over their natural twins such as better control over synthesis, physicochemical properties and target binding. Fast and convergent synthesis pathways are underdeveloped. Multicomponent reaction (MCR) chemistry is very well suited for the synthesis of a diverse range of macrocycles and is a...
Source: Drug Discovery Today: Technologies - July 12, 2018 Category: Drugs & Pharmacology Source Type: research
Inflammation and DNA damage: Probing pathways to cancer and neurodegeneration
Publication date: November 2017Source: Drug Discovery Today: Technologies, Volume 25Author(s): Mehran Makvandi, Mark A. Sellmyer, Robert H. MachCancer and neurodegeneration represent two opposite ends of the biological spectrum but contain many common biological mechanisms. Two such mechanisms include the elevated levels of oxidative stress and DNA damage. In this brief review, we describe current approaches for imaging these biological pathways with the molecular imaging technique, Positron Emission Tomography (PET), and the potential of PET imaging studies to measure the efficacy of anticancer drugs and strategies for de...
Source: Drug Discovery Today: Technologies - July 10, 2018 Category: Drugs & Pharmacology Source Type: research
Use of carbon-11 labelled tool compounds in support of drug development
Publication date: November 2017Source: Drug Discovery Today: Technologies, Volume 25Author(s): Giulia Boscutti, Mickael Huiban, Jan PasschierThe pharmaceutical industry is facing key challenges to improve return on R&D investment. Positron emission tomography (PET), by itself or in combination with complementary technologies such as magnetic resonance imaging (MRI), provides a unique opportunity to confirm a candidate’s ability to meet the so-called ‘three pillars’ of drug development. Positive confirmation provides confidence for go/no-go decision making at an early stage of the development process and enables infor...
Source: Drug Discovery Today: Technologies - July 10, 2018 Category: Drugs & Pharmacology Source Type: research
