The Role Of Proteomics In Drug Discovery And Development (1).pptx

The Role Of Proteomics In Drug Discovery And Development

1. The Role Of Proteomics In Drug Discovery And Development Presented By- Chandan Sarma Sourabh Kr Roy Semima Nasrin Students of B.sc 5 th Semester

2. CONTENT Introduction Proteomics Biomarkers Types of proteomics P rinciple of mass spectrometry (MS) Working of mass spectrometry (MS) Proteomics image Steps of drug discovery process Application of proteomics in drug target discovery Important aspects of proteomics in drug development: Post-translational modification analysis Plant drugs discovered by using proteomics

3. INTRODUCTION Proteome indicates the total proteins expressed by a genome in a cell or tissue . Biomarkers detection might allow identification of patients who would benefit from further evaluation. With the development of proteomic techniques, proteome analysis provides a fast, non-invasive diagnostic tool for patients with various diseases . The advent of highly sensitive proteomic technologies can identify proteins associated with development of diseases well before any clinically identifiable alteration.

4. PROTEOMICS Proteome is a blend of the words "protein" and "genome". It was coined in 1994 by then- Ph.D student  Marc Wilkins  at Macquarie University, which founded the first dedicated proteomics laboratory in 1995. Proteome defines as the complete set of proteins expressed during a cell's entire lifetime . Proteomics is the study of the proteome; it uses technologies ranging from genetic analysis to mass spectrometry. Proteomics assesses activities, modifications, localization, and interactions of proteins in complexes .

5. Proteomics is the large-scale study of proteins, focusing on their structure, function, and interactions within a cell or organism. It involves analyzing the entire set of proteins, known as the proteome, in a given system. Proteomics is essentially protein analysis. Could be described as a broad classification for a set of technology and bioinformatics platforms aimed at the comprehensive molecular description of the actual protein complement of a given sample.

6. BIOMARKERS Biomarkers in Medicine. Biomarkers are disease-related proteins or biochemical indicators used to diagnose, monitor disease activity, prognosis, and development. They guide molecular target treatment or evaluation of therapeutic response. Commonly used biomarkers include PSA (prostate specific antigen).

7. Proteomics in Biomarker Discovery Proteomics technology is used for biomarker discovery by analyzing global protein profiling in body fluids. 2D-PAGE is the simplest approach used in biomarker discovery. Disease-Specific Biomarkers Diagnostic biomarkers are used for early disease detection. Prognostic biomarkers predict disease recurrence and patient response to treatment. Predictive biomarkers classify patients into responder and non-responder groups.

8. Proteomics in Disease Progression Only 2% of human diseases are due to a single gene damage, with 98% due to epigenetic and environmental factors. Despite high interest, high investigation burdens, and publications, few identified biomarkers using proteomics technology have been validated and approved by FDA for clinical usage.

9. TYPES OF PROTEOMICS Structural Proteomics :-Structural proteomics deals with the study of structure and nature of protein complexes present in a particular cell organelle. Functional proteomics :- It refers to the use of proteomics techniques to analyze the characteristics of molecular protein-networks involved in a living cell . Expression proteomics :- It refers to the quantitative study of protein expression between sample differing by some variable.

10. Principle of Mass Spectrometry (MS) 1)In this technique, molecules are bombarded with a beam of energetic electrons. 2)The molecules are ionized and broken up into many fragments, some of which are positive ions. Each kind of ion has a particular ratio of mass to charge, i.e. m/e ratio (value). 3)For most ions, the charge is one, and thus, the m/e ratio is simply the molecular mass of the ion. 4)The ions pass through magnetic and electric fields to reach the detector where they are detected and signals are recorded to give mass spectra.

11. Working of Mass Spectrometry (MS)

12. PROTEOMICS IMAGE Proteomics image typically refers to visual representations or analyses in the field of proteomics. Proteomics is the large-scale study of proteins, particularly their functions, structures, and interactions. Images in proteomics can come from various types of techniques and tools used to study proteins. Fig: 2-D Electrophoresis

13. Steps of Drug Discovery Process

14. Application of proteomics in drug target discovery Proteomics is the large-scale study of the proteins in a cell, tissue, or entire organism . Compare changes in protein levels in normal and diseased tissue . One established technique for comparative proteomics is based on labelling proteins from normal and diseased tissues with different fluorescent dyes (Cy3 and Cy5), mixing the proteins together, and then separating them by isoelectric point and molecular weight (difference in-gel electrophoresis ).

15. The sequencing of the human genome has increased interest in proteomics because while DNA sequence information provides a static snapshot of the various ways in which the cell might use its proteins, the life of the cell is a dynamic process . This new data increase the interest of proteomics in the field of science, medicine, and most notably – pharmaceuticals. Proteomics can analyze biomarkers by quantifying individual proteins and show the separation between one or more protein "spots" on a scanned image from two- dimensional gel electrophoresis; for example, proteomic differences between early and advanced stages of an illness can be observed

16. DISEASE Proteins explored through proteomics Alzheimer’s disease Sulfatide , β -amyloid precursor Breast cancer Human epidermal growth factor receptor 2 ( HER-2) Gliomas Receptor protein tyrosine phosphate-B Ischemic heart disease Troponin , Natriuretic peptide Prostate cancer Annexin Tumor hypoxia IKK- β

17. Important aspects of proteomics in drug development: High-throughput analysis : High-throughput technology has revolutionized proteomics and metabolomics, dividing it into three phases: discovery, network-analysis, and clinical proteomics. Discovery involves identifying amino acid sequences and protein structures, network-analysis builds global signaling networks, and clinical proteomics develops clinical assays. Common high-throughput proteomic techniques include mass spectrometry, protein pathway array, tissue microarrays, and Luminex .

18. QUANTITATIVE PROTEOMICS : Quantitative proteomics  is an analytical chemistry technique for determining the amount of  proteins  in a sample. The methods for protein identification are identical to those used in general (i.e. qualitative) proteomics, but include quantification as an additional dimension pression levels. Quantitative proteomics has the largest applications in the protein target identification, protein target validation, and toxicity profiling of drug discovery. Drug discovery has been used to investigate protein-protein interaction and, more recently, drug-small molecule interactions, a field of study called  chemoproteomics .

19. Fig: Quantitative mass spectrometry.

20. Post-translational modification analysis : Proteomics can identify modifications like phosphorylation, glycosylation, and ubiquitination which can significantly impact protein function. Post-translational modification (PTM) analysis of proteomics is a study of the covalent changes that proteins undergo after biosynthesis. These changes can include the addition of proteins or functional groups, cleavage of regulatory subunits, or degradation of proteins. PTMs can affect the physical and chemical properties of proteins, which in turn can change their biological activity, function and disease progression.

21. Plant drugs discovered by using proteomics : DISEASE PLANT NAME Diabetes Chrysobalanus icaco Family : Chrysobalanaceae (common name: cocoplum , fat pork) 2. Bacterium Pseudomonas Aeruginosa (causes a wide spectrum of infections with varying severity) Medicago truncatula Family : Legumes (common name: Barrel clover)

22. 3. Chronic pain Cannabis sativa Family : Cannabaceae 4 . Physiological disorders such as diabetes, heart disease, cancer, and neurodegeneration Panax ginseng Family: Araliaceae 5. Tonsillitis, cholelithiasis , and conjunctivitis Clematis terniflora Family: Ranunculaceae

23. 6. Anticancer drug paclitaxel Taxus brevifolia Family: Taxaceae 7. Neutralize bone degeneration caused by rheumatoid arthritis in rats Achyranthes aspera Family: Amaranthaceae 8. Antimicrobial, antiviral, anti-inflammatory, and antitumor Scutellaria baicalensis Family: Lamiaceae

24. CONCLUSION Proteomics: A Tool for Early Disease Diagnosis • Characterizes protein components and changes during production. • Identifies disease-related biomarkers and drug targets. • Combines peptidomics , metabolomics, and bioinformatics for systemic disease study. • Elucidates complex biosynthetic pathways of plant bioactive compounds. • Describes external factors affecting pathways. • Shows responses in animals treated with plant-derived natural products.

25. REFERENCE https :// www.creative-proteomics.com/services/imaging-analysis.htm https:// www.nature.com/articles/s41374-022-00830-7 https:// portlandpress.com/clinsci/article-abstract/109/5/421/68013/Towards-the-application-of-proteomics-in-renal https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6269565 / https:// www.researchgate.net/publication/234091027_Proteomics_in_Drug_Discovery https:// www.slideshare.net/slideshow/plant-drug-cultivation-durgashree-diwakar/253567591 https:// en.wikipedia.org/wiki/Quantitative_proteomics https:// www.creative-proteomics.com/services/imaging-analysis.htm https:// proteome.gs.washington.edu/classes/Genome490/Class3.pdf

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