The current role and evolution of X-ray crystallography in drug discovery and development DOI
Vanessa Bijak, Michal Szczygiel, Joanna Lenkiewicz

et al.

Expert Opinion on Drug Discovery, Journal Year: 2023, Volume and Issue: 18(11), P. 1221 - 1230

Published: Aug. 17, 2023

Macromolecular X-ray crystallography and cryo-EM are currently the primary techniques used to determine three-dimensional structures of proteins, nucleic acids, viruses. Structural information has been critical drug discovery structural bioinformatics. The integration artificial intelligence (AI) into shown great promise in automating accelerating analysis complex data, further improving efficiency accuracy structure determination.

Language: Английский

Immunotherapeutic targeting of surfaceome heterogeneity in AML DOI Creative Commons

Marie-Ève Bordeleau,

Éric Audemard,

Arnaud Métois

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(6), P. 114260 - 114260

Published: June 1, 2024

Immunotherapy remains underexploited in acute myeloid leukemia (AML) compared to other hematological malignancies. Currently, gemtuzumab ozogamicin is the only therapeutic antibody approved for this disease. Here, identify potential targets immunotherapeutic intervention, we analyze surface proteome of 100 genetically diverse primary human AML specimens identification cell proteins and conduct single-cell transcriptome analyses on a subset these assess antigen expression at sub-population level. Through comprehensive effort, successfully numerous antigens markers preferentially expressed by primitive cells. Many identified are targeted antibodies currently under clinical evaluation various cancer types, highlighting value approach. Importantly, initiative uncovers heterogeneity surfaceome level, identifies several characterizing subgroups, positions immunotherapy as promising approach target subgroup specificities.

Language: Английский

Citations

9

High-Throughput Single-Molecule Surface-Enhanced Raman Spectroscopic Profiling of Single-Amino Acid Substitutions in Peptides by a Gold Plasmonic Nanopore DOI
Wang Li, Linru Guo,

Xin‐Lei Ding

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(29), P. 19200 - 19207

Published: July 12, 2024

Simultaneous detection and structural characterization of protein variants on a single platform are highly desirable but technically challenging. Herein, we present single-molecule spectral system based gold plasmonic nanopore for analyzing two peptides their single-point mutated variants. The enabled the high-throughput acquisition surface-enhanced Raman scattering (SERS) spectra at level by electrically driving analytes into hot spots. Furthermore, statistical method Boolean operations was developed to extract prominent features from fluctuated SERS spectra. effects single-amino acid substitutions both intramolecular interactions peptide conformations were directly characterized system, results agreed with predictions AlphaFold2. This study highlights mutual benefits spectroscopy technology, whereby offers powerful tool analysis proteins.

Language: Английский

Citations

9

Toward a comprehensive profiling of alternative splicing proteoform structures, interactions and functions DOI Creative Commons
Élodie Laine, María I. Freiberger

Current Opinion in Structural Biology, Journal Year: 2025, Volume and Issue: 90, P. 102979 - 102979

Published: Jan. 7, 2025

The mRNA splicing machinery has been estimated to generate 100,000 known protein-coding transcripts for 20,000 human genes (Ensembl, Sept. 2024). However, this set is expanding with the massive and rapidly growing data coming from high-throughput technologies, particularly single-cell long-read sequencing. Yet, implications of complexity at protein level remain largely uncharted. In review, we describe current advances toward systematically assessing contribution alternative proteome function diversification. We discuss potential challenges using artificial intelligence-based techniques in identifying proteoforms characterising their structures, interactions, functions.

Language: Английский

Citations

1

Proteomic Profiling Towards a Better Understanding of Genetic Based Muscular Diseases: The Current Picture and a Look to the Future DOI Creative Commons
Marc Pauper, Andreas Hentschel, Malte Tiburcy

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(1), P. 130 - 130

Published: Jan. 15, 2025

Proteomics accelerates diagnosis and research of muscular diseases by enabling the robust analysis proteins relevant for manifestation neuromuscular in following aspects: (i) evaluation effect genetic variants on corresponding protein, (ii) prediction underlying defect based proteomic signature muscle biopsies, (iii) pathophysiologies different entities diseases, key definition new intervention concepts, (iv) patient stratification according to biochemical fingerprints as well (v) monitoring success therapeutic interventions. This review presents—also through exemplary case studies—the various advantages mass proteomics investigation discusses technical limitations, provides an outlook possible future application concepts. Hence, is excellent large-scale analytical tool diagnostic workup (hereditary) warrants systematic profiling pathophysiological processes. The steady development may allow overcome existing limitations including a quenched dynamic range quantification protein isoforms. Future directions include targeted settings using not only biopsies but also liquid address need minimally invasive procedures.

Language: Английский

Citations

1

The current role and evolution of X-ray crystallography in drug discovery and development DOI
Vanessa Bijak, Michal Szczygiel, Joanna Lenkiewicz

et al.

Expert Opinion on Drug Discovery, Journal Year: 2023, Volume and Issue: 18(11), P. 1221 - 1230

Published: Aug. 17, 2023

Macromolecular X-ray crystallography and cryo-EM are currently the primary techniques used to determine three-dimensional structures of proteins, nucleic acids, viruses. Structural information has been critical drug discovery structural bioinformatics. The integration artificial intelligence (AI) into shown great promise in automating accelerating analysis complex data, further improving efficiency accuracy structure determination.

Language: Английский

Citations

18