Special Issue "High Field NMR and Ultra-High Field NMR in Medicinal Chemistry"

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: 30 April 2022.

Special Issue Editors

Prof. Dr. Jesus Jimenez-Barbero
E-Mail Website
Guest Editor
1. CIC bioGUNE, Bizkaia Technology Park, Building 800, 48160 Derio, Spain
2. Ikerbasque, Basque Foundation for Science, Maria López de Haro 3, 48013 Bilbao, Spain
Interests: NMR; molecular recognition; glycans; protein-ligand interactions; chemical biology; medicinal chemistry; infectious diseases; cancer; rare diseases; metabolomics
Special Issues, Collections and Topics in MDPI journals
Dr. Óscar Millet
E-Mail Website
Guest Editor
CIC bioGUNE, Bizkaia Technology Park, Building 800, 48160 Derio, Spain
Interests: NMR; molecular recognition; glycans; protein-ligand interactions; chemical biology; medicinal chemistry; infectious diseases; cancer; rare diseases; metabolomics

Special Issue Information

Dear Colleagues,

Nuclear magnetic resonance (NMR) has gained a tremendous impact in life sciences, including medicinal chemistry and drug discovery. The enormous variety of available experiments and protocols allow characterizing essential features of the different actors in these fields. The arrival of very high field and ultra high field (UHF) spectrometers, beyond 16 Tesla, has boosted its applications in the area, both using solution and solid state methodologies.

Applications of UHF to the identification of the structure and conformation of the partners: drugs (from small-medium size molecules to biologicals) and partners (either protein receptor, enzyme, nucleic acid, or antibody) to monitor and understand dynamics and allostery, also in intrinsically disordered proteins, show the immense power of the technique.

The challenges for applying NMR are expanding year after year. Probably, one of the frontiers is to use NMR methodologies alone, or in combination with other techniques, to translate the information obtained in vitro to the in vivo situation. For that, diverse methodologies using UHF aim at understanding, and then manipulating, the functional response behind the interactions of the biomacromolecules and their assemblies with their partners, using in vitro experiments, membranes or their mimics, and even whole cells. In a parallel manner, NMR-based metabolomics is also rapidly growing as a powerful method for precision medicine applications, since it allows identifying biomarkers for diagnosis, recognizing and measuring

The journal Pharmaceuticals invites both reviews and original articles shedding light on the applications of High Field NMR and Ultra-high Field NMR in scientific problems on topics mentioned above, related to Chemical Biology and Medicinal Chemistry. Topics include: protein-ligand, protein-nucleic acid, protein-glycan, and protein-protein interactions, methodological aspects of NMR, NMR-based metabolomics, in-cell and on-cell NMR, NMR-based ligand/fragment screening. The collection of manuscripts will be published as a Special Issue of the journal.

Prof. Dr. Jesus Jimenez-Barbero
Dr. Óscar Millet
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • NMR
  • molecular recognition
  • receptor-ligand interactions
  • NMR-based metabolomics

Published Papers (5 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Other

Article
Zinc Binding to NAP-Type Neuroprotective Peptides: Nuclear Magnetic Resonance Studies and Molecular Modeling
Pharmaceuticals 2021, 14(10), 1011; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14101011 - 01 Oct 2021
Viewed by 547
Abstract
Aggregation of amyloid-β peptides (Aβ) is a hallmark of Alzheimer’s disease (AD), which is affecting an increasing number of people. Hence, there is an urgent need to develop new pharmaceutical treatments which could be used to prevent the AD symptomatology. Activity-dependent neuroprotective protein [...] Read more.
Aggregation of amyloid-β peptides (Aβ) is a hallmark of Alzheimer’s disease (AD), which is affecting an increasing number of people. Hence, there is an urgent need to develop new pharmaceutical treatments which could be used to prevent the AD symptomatology. Activity-dependent neuroprotective protein (ADNP) was found to be deficient in AD, whereas NAP, an 8-amino-acid peptide (1NAPVSIPQ8) derived from ADNP, was shown to enhance cognitive function. The higher tendency of zinc ion to induce Aβ aggregation and formation of amorphous aggregates is also well-known in the scientific literature. Although zinc binding to Aβ peptides was extensively investigated, there is a shortage of knowledge regarding the relationship between NAP peptide and zinc ions. Therefore, here, we investigated the binding of zinc ions to the native NAP peptide and its analog obtained by replacing the serine residue in the NAP sequence with tyrosine (1NAPVYIPQ8) at various molar ratios and pH values by mass spectrometry (MS) and nuclear magnetic resonancespectroscopy (NMR). Matrix-assisted laser desorption/ionization time-of-flight (MALDI ToF) mass spectrometry confirmed the binding of zinc ions to NAP peptides, while the chemical shift of Asp1, observed in 1H-NMR spectra, provided direct evidence for the coordinating role of zinc in the N-terminal region. In addition, molecular modeling has also contributed largely to our understanding of Zn binding to NAP peptides. Full article
(This article belongs to the Special Issue High Field NMR and Ultra-High Field NMR in Medicinal Chemistry)
Show Figures

Graphical abstract

Article
Semaphorin 3A—Glycosaminoglycans Interaction as Therapeutic Target for Axonal Regeneration
Pharmaceuticals 2021, 14(9), 906; https://doi.org/10.3390/ph14090906 - 07 Sep 2021
Viewed by 1072
Abstract
Semaphorin 3A (Sema3A) is a cell-secreted protein that participates in the axonal guidance pathways. Sema3A acts as a canonical repulsive axon guidance molecule, inhibiting CNS regenerative axonal growth and propagation. Therefore, interfering with Sema3A signaling is proposed as a therapeutic target for achieving [...] Read more.
Semaphorin 3A (Sema3A) is a cell-secreted protein that participates in the axonal guidance pathways. Sema3A acts as a canonical repulsive axon guidance molecule, inhibiting CNS regenerative axonal growth and propagation. Therefore, interfering with Sema3A signaling is proposed as a therapeutic target for achieving functional recovery after CNS injuries. It has been shown that Sema3A adheres to the proteoglycan component of the extracellular matrix (ECM) and selectively binds to heparin and chondroitin sulfate-E (CS-E) glycosaminoglycans (GAGs). We hypothesize that the biologically relevant interaction between Sema3A and GAGs takes place at Sema3A C-terminal polybasic region (SCT). The aims of this study were to characterize the interaction of the whole Sema3A C-terminal polybasic region (Sema3A 725–771) with GAGs and to investigate the disruption of this interaction by small molecules. Recombinant Sema3A basic domain was produced and we used a combination of biophysical techniques (NMR, SPR, and heparin affinity chromatography) to gain insight into the interaction of the Sema3A C-terminal domain with GAGs. The results demonstrate that SCT is an intrinsically disordered region, which confirms that SCT binds to GAGs and helps to identify the specific residues involved in the interaction. NMR studies, supported by molecular dynamics simulations, show that a new peptoid molecule (CSIC02) may disrupt the interaction between SCT and heparin. Our structural study paves the way toward the design of new molecules targeting these protein–GAG interactions with potential therapeutic applications. Full article
(This article belongs to the Special Issue High Field NMR and Ultra-High Field NMR in Medicinal Chemistry)
Show Figures

Graphical abstract

Article
Exploring the Early Stages of the Amyloid Aβ(1–42) Peptide Aggregation Process: An NMR Study
Pharmaceuticals 2021, 14(8), 732; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14080732 - 27 Jul 2021
Viewed by 879
Abstract
Alzheimer’s disease (AD) is a neurodegenerative pathology characterized by the presence of neurofibrillary tangles and amyloid plaques, the latter mainly composed of Aβ(1–40) and Aβ(1–42) peptides. The control of the Aβ aggregation process as a therapeutic strategy for AD has prompted the interest [...] Read more.
Alzheimer’s disease (AD) is a neurodegenerative pathology characterized by the presence of neurofibrillary tangles and amyloid plaques, the latter mainly composed of Aβ(1–40) and Aβ(1–42) peptides. The control of the Aβ aggregation process as a therapeutic strategy for AD has prompted the interest to investigate the conformation of the Aβ peptides, taking advantage of computational and experimental techniques. Mixtures composed of systematically different proportions of HFIP and water have been used to monitor, by NMR, the conformational transition of the Aβ(1–42) from soluble α-helical structure to β-sheet aggregates. In the previous studies, 50/50 HFIP/water proportion emerged as the solution condition where the first evident Aβ(1–42) conformational changes occur. In the hypothesis that this solvent reproduces the best condition to catch transitional helical-β-sheet Aβ(1–42) conformations, in this study, we report an extensive NMR conformational analysis of Aβ(1–42) in 50/50 HFIP/water v/v. Aβ(1–42) structure was solved by us, giving evidence that the evolution of Aβ(1–42) peptide from helical to the β-sheet may follow unexpected routes. Molecular dynamics simulations confirm that the structural model we calculated represents a starting condition for amyloid fibrils formation. Full article
(This article belongs to the Special Issue High Field NMR and Ultra-High Field NMR in Medicinal Chemistry)
Show Figures

Figure 1

Other

Jump to: Research

Systematic Review
Pharmacometabolomics by NMR in Oncology: A Systematic Review
Pharmaceuticals 2021, 14(10), 1015; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14101015 - 02 Oct 2021
Viewed by 745
Abstract
Pharmacometabolomics (PMx) studies aim to predict individual differences in treatment response and in the development of adverse effects associated with specific drug treatments. Overall, these studies inform us about how individuals will respond to a drug treatment based on their metabolic profiles obtained [...] Read more.
Pharmacometabolomics (PMx) studies aim to predict individual differences in treatment response and in the development of adverse effects associated with specific drug treatments. Overall, these studies inform us about how individuals will respond to a drug treatment based on their metabolic profiles obtained before, during, or after the therapeutic intervention. In the era of precision medicine, metabolic profiles hold great potential to guide patient selection and stratification in clinical trials, with a focus on improving drug efficacy and safety. Metabolomics is closely related to the phenotype as alterations in metabolism reflect changes in the preceding cascade of genomics, transcriptomics, and proteomics changes, thus providing a significant advance over other omics approaches. Nuclear Magnetic Resonance (NMR) is one of the most widely used analytical platforms in metabolomics studies. In fact, since the introduction of PMx studies in 2006, the number of NMR-based PMx studies has been continuously growing and has provided novel insights into the specific metabolic changes associated with different mechanisms of action and/or toxic effects. This review presents an up-to-date summary of NMR-based PMx studies performed over the last 10 years. Our main objective is to discuss the experimental approaches used for the characterization of the metabolic changes associated with specific therapeutic interventions, the most relevant results obtained so far, and some of the remaining challenges in this area. Full article
(This article belongs to the Special Issue High Field NMR and Ultra-High Field NMR in Medicinal Chemistry)
Show Figures

Graphical abstract

Concept Paper
Real-Time Non-Invasive and Direct Determination of Lactate Dehydrogenase Activity in Cerebral Organoids—A New Method to Characterize the Metabolism of Brain Organoids?
Pharmaceuticals 2021, 14(9), 878; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14090878 - 30 Aug 2021
Viewed by 985
Abstract
Organoids are a powerful tool in the quest to understand human diseases. As the developing brain is extremely inaccessible in mammals, cerebral organoids (COs) provide a unique way to investigate neural development and related disorders. The aim of this study was to utilize [...] Read more.
Organoids are a powerful tool in the quest to understand human diseases. As the developing brain is extremely inaccessible in mammals, cerebral organoids (COs) provide a unique way to investigate neural development and related disorders. The aim of this study was to utilize hyperpolarized 13C NMR to investigate the metabolism of COs in real-time, in a non-destructive manner. The enzymatic activity of lactate dehydrogenase (LDH) was determined by quantifying the rate of [1-13C]lactate production from hyperpolarized [1-13C]pyruvate. Organoid development was assessed by immunofluorescence imaging. Organoid viability was confirmed using 31P NMR spectroscopy. A total of 15 organoids collated into 3 groups with a group total weight of 20–77 mg were used in this study. Two groups were at the age of 10 weeks and one was at the age of 33 weeks. The feasibility of this approach was demonstrated in both age groups, and the LDH activity rate was found to be 1.32 ± 0.75 nmol/s (n = 3 organoid batches). These results suggest that hyperpolarized NMR can be used to characterize the metabolism of brain organoids with a total tissue wet weight of as low as 20 mg (<3 mm3) and a diameter ranging from 3 to 6 mm. Full article
(This article belongs to the Special Issue High Field NMR and Ultra-High Field NMR in Medicinal Chemistry)
Show Figures

Figure 1

Back to TopTop