Editorial for the special issue on “constrained peptides”
Publication date: December 2017 Source:Drug Discovery Today: Technologies, Volume 26 Author(s): Jan H. van Maarseveen, Peter Timmerman (Source: Drug Discovery Today: Technologies)
Source: Drug Discovery Today: Technologies - December 15, 2017 Category: Drugs & Pharmacology Source Type: research
Protein –protein and protein–chromatin interactions of LEDGF/p75 as novel drug targets
Publication date: June 2017 Source:Drug Discovery Today: Technologies, Volume 24 Author(s): Jolien Blokken, Jan De Rijck, Frauke Christ, Zeger Debyser Lens epithelium-derived growth factor p75 (LEDGF/p75), a transcriptional co-activator, plays an important role in tethering protein complexes to the chromatin. Through this tethering function LEDGF/p75 is implicated in a diverse set of human diseases including HIV infection and mixed lineage leukemia, an aggressive form of cancer with poor prognosis. Here we provide an overview of recent progress in resolving protein–protein and protein–chromatin interaction mechan...
Source: Drug Discovery Today: Technologies - December 12, 2017 Category: Drugs & Pharmacology Source Type: research
Protein –Protein Interactions
Publication date: June 2017 Source:Drug Discovery Today: Technologies, Volume 24 Author(s): Christian Ottmann (Source: Drug Discovery Today: Technologies)
Source: Drug Discovery Today: Technologies - December 12, 2017 Category: Drugs & Pharmacology Source Type: research
Discovery and development of SV2A PET tracers: Potential for imaging synaptic density and clinical applications
Publication date: November 2017 Source:Drug Discovery Today: Technologies, Volume 25 Author(s): Joel Mercier, Laurent Provins, Anne Valade Imaging synaptic density in vivo has promise for numerous research and clinical applications in the diagnosis and treatment monitoring of neurodegenerative and psychiatric diseases. Recent developments in the field of PET, such as SV2A human imaging with the novel tracers UCB-A, UCB-H and UCB-J, may help in realizing this potential and bring significant benefit for the patients suffering from these diseases. This review provides an overview of the most recent progress in the field ...
Source: Drug Discovery Today: Technologies - December 12, 2017 Category: Drugs & Pharmacology Source Type: research
Inflammation and DNA damage: Probing pathways to cancer and neurodegeneration
Publication date: November 2017 Source:Drug Discovery Today: Technologies, Volume 25 Author(s): Mehran Makvandi, Mark A. Sellmyer, Robert H. Mach Cancer 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...
Source: Drug Discovery Today: Technologies - December 12, 2017 Category: Drugs & Pharmacology Source Type: research
Use of carbon-11 labelled tool compounds in support of drug development
Publication date: November 2017 Source:Drug Discovery Today: Technologies, Volume 25 Author(s): Giulia Boscutti, Mickael Huiban, Jan Passchier The 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 an...
Source: Drug Discovery Today: Technologies - December 12, 2017 Category: Drugs & Pharmacology Source Type: research
In vivo molecular imaging tools facilitate drug discovery
Publication date: November 2017 Source:Drug Discovery Today: Technologies, Volume 25 Author(s): Yves P. Auberson (Source: Drug Discovery Today: Technologies)
Source: Drug Discovery Today: Technologies - December 12, 2017 Category: Drugs & Pharmacology Source Type: research
Enzyme-catalyzed peptide cyclization
Publication date: Available online 26 November 2017 Source:Drug Discovery Today: Technologies Author(s): Marcel Schmidt, Ana Toplak, Peter J.L.M. Quaedflieg, Jan H. van Maarseveen, Timo Nuijens The recent advancement of peptide macrocycles as promising therapeutics creates a need for novel methodologies for their efficient synthesis and (large scale) production. Within this context, due to the favorable properties of biocatalysts, enzyme-mediated methodologies have gained great interest. Enzymes such as sortase A, butelase 1, peptiligase and omniligase-1 represent extremely powerful and valuable enzymatic tools for ...
Source: Drug Discovery Today: Technologies - December 12, 2017 Category: Drugs & Pharmacology Source Type: research
Tools to investigate the ubiquitin proteasome system
Publication date: Available online 26 November 2017 Source:Drug Discovery Today: Technologies Author(s): Yves Leestemaker, Huib Ovaa Ubiquitin is a 76-amino acid regulatory protein involved in many important cellular processes. Ubiquitin can be attached to other proteins at either a lysine residue or to the N-terminus by the consecutive actions of E1, E2, and E3 enzymes. Ubiquitin can also be attached to itself, resulting in poly-ubiquitin chains. Ubiquitination affects substrate proteins in different ways, for example by resulting in degradation of the substrate protein by the 26S proteasome. Ubiquitination can be rev...
Source: Drug Discovery Today: Technologies - December 12, 2017 Category: Drugs & Pharmacology Source Type: research
Constrained cell penetrating peptides
Publication date: Available online 27 November 2017 Source:Drug Discovery Today: Technologies Author(s): S.A. Bode, D.W.P.M. Löwik In this review we provide an overview of recent developments in the field of cell penetrating peptides (CPPs) on research that aims to achieve better control over their transduction properties – one of the big challenges – by means of restraining them. Three different constraining strategies are presented: triggerable activation, backbone rigidification and macrocyclization. Each of these methods have their opportunities in gaining control over CPP activity and selectivity. (Source: Dr...
Source: Drug Discovery Today: Technologies - December 12, 2017 Category: Drugs & Pharmacology Source Type: research
Recent advances in the synthesis of cyclic pseudopeptides
Publication date: Available online 6 December 2017 Source:Drug Discovery Today: Technologies Author(s): Serge Zaretsky, Andrei K. Yudin Constrained peptides pose tremendous value in drug discovery. For example, owing to their large surface areas, they offer novel ways at inhibiting protein–protein interactions. As this field has grown, it has become desirable to introduce non-peptidic functionality into these rings to enable differentiated structure activity relationships and improved pharmacokinetic properties. Recent advances in the synthesis of cyclic pseudopeptides include macrocyclization through cysteine alkyla...
Source: Drug Discovery Today: Technologies - December 12, 2017 Category: Drugs & Pharmacology Source Type: research
Identification of nonstandard macrocyclic peptide ligands through display screening
Publication date: Available online 15 November 2017 Source:Drug Discovery Today: Technologies Author(s): Rhys Dylan Taylor, Matias Rey-Carrizo, Toby Passioura, Hiroaki Suga Techniques facilitating the synthesis and screening of very high diversity nonstandard macrocyclic peptide libraries have led to such compounds receiving increasing attention as potential drug candidates. Specifically, approaches which allow the use of non-proteinogenic amino acids are proving to be particularly effective, since they expand the accessible chemical space of the starting library and thus allow the identification of compounds with st...
Source: Drug Discovery Today: Technologies - November 17, 2017 Category: Drugs & Pharmacology Source Type: research
Discovery of PET radiopharmaceuticals at the academia-industry interface
Publication date: Available online 23 October 2017 Source:Drug Discovery Today: Technologies Author(s): Vadim Bernard-Gauthier, Thomas L. Collier, Steven H. Liang, Neil Vasdev Project-specific collaborations between academia and pharmaceutical partners are a growing phenomenon within molecular imaging and in particular in the positron emission tomography (PET) radiopharmaceutical community. This cultural shift can be attributed in part to decreased public funding in academia in conjunction with the increased reliance on outsourcing of chemistry, radiochemistry, pharmacology and molecular imaging studies by the pharma...
Source: Drug Discovery Today: Technologies - November 10, 2017 Category: Drugs & Pharmacology Source Type: research
Medicinal Chemistry strategies for PET tracer discovery
Publication date: Available online 26 October 2017 Source:Drug Discovery Today: Technologies Author(s): José Ignacio Andrés, Mark Schmidt The detection of gamma rays, resulting from decay of positron emitting isotopes, allows exquisitely sensitive detection of probes radiolabeled with such isotopes. These probes can be designed for high affinity binding to specific molecular targets and be used as tools in the early development of drugs, particularly for neuropsychiatric disorders. Availability of novel tracers requires dedicated resources and selection assays. Many of the selection assays are similar to those used f...
Source: Drug Discovery Today: Technologies - November 10, 2017 Category: Drugs & Pharmacology Source Type: research
Novel approaches to targeting BRD4
Publication date: Available online 28 October 2017 Source:Drug Discovery Today: Technologies Author(s): Olesya A. Kharenko, Henrik C. Hansen Inhibition of bromo and extra-terminal (BET) bromodomains, including BRD4, has emerged as a new exciting epigenetic target for oncology, in particular. Recently, novel alternatives to the traditional use of reversible small molecules have emerged, including proteolytic targeting BET agents and irreversible binding inhibitors. These alternatives to reversible inhibitors may offer some advantage and can be used as tools to further decipher the underlying biology. Supportive pre-clin...
Source: Drug Discovery Today: Technologies - November 10, 2017 Category: Drugs & Pharmacology Source Type: research
