Handbook of experimental pharmacology最新文献

The Road Toward Nanopore Sequencing of Glycosaminoglycans. 糖胺聚糖纳米孔测序之路。

Handbook of experimental pharmacology Pub Date : 2025-05-30 DOI: 10.1007/164_2025_750

Wesley Pietsch, Tom Schumann, Marc Safferthal, Niklas Geue, Kevin Pagel, Michael Götze

引用次数: 0

Handbook of experimental pharmacology Pub Date : 2025-05-30 DOI: 10.1007/164_2025_751

Henrique Oliveira Duarte, Celso Albuquerque Reis, Veronique Blanchard, Rudolf Tauber

{"title":"Glycosylation in Cancer.","authors":"Henrique Oliveira Duarte, Celso Albuquerque Reis, Veronique Blanchard, Rudolf Tauber","doi":"10.1007/164_2025_751","DOIUrl":"https://doi.org/10.1007/164_2025_751","url":null,"abstract":"Structural alterations of the glycan chains attached to glycoproteins and glycolipids are present in all types of malignomas investigated to date, including adenocarcinomas, sarcomas and haematological malignancies. They occur in humans as well as in animals including experimental models of malignancy, regardless of the type, cause, or stage of the tumour. The biochemical and genomic characterization of the enzymatic machineries involved in glycan biosynthesis in cancer cells shows that tumour-associated glycosylation changes are a critical part of tumour initiation and progression. Experimental studies and epidemiological findings give clear evidence that tumour-associated glycans bear functional significance in the invasive and metastatic growth of malignancies, for immunological tumour defence and, hence, influence the clinical outcome and the prognosis of cancer patients. Tumour-associated glycan changes are, moreover, targets for new pharmacological and immunological therapy methods and serve as important clinical biomarkers for diagnosis, particularly for monitoring disease progression and therapeutic efficacy. This chapter provides an overview of the major types of changes of glycosylation, genetic and biochemical mechanisms contributing to cancer-associated glycosylation, functional consequences for tumour growth and the clinical significance in cancer diagnosis, monitoring and treatment.","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Breadth of Pharmacology Modeling: Fundamentals of Pharmacokinetics, Pharmacodynamics, and Mechanistic Modeling. 药理学建模的广度：药代动力学、药效学和机制建模的基础。

Handbook of experimental pharmacology Pub Date : 2025-05-06 DOI: 10.1007/164_2025_746

Donald E Mager

{"title":"Breadth of Pharmacology Modeling: Fundamentals of Pharmacokinetics, Pharmacodynamics, and Mechanistic Modeling.","authors":"Donald E Mager","doi":"10.1007/164_2025_746","DOIUrl":"https://doi.org/10.1007/164_2025_746","url":null,"abstract":"The basic principles of pharmacokinetics and pharmacodynamics represent the foundational knowledge base upon which complex quantitative systems pharmacology models of drug action are built. This chapter provides a high-level overview of fundamental factors that determine the disposition and physiological responses to drugs and the application of compartmental models to characterize the time-course of drug exposure and pharmacological effects. Many of these processes are subject to capacity-limitation, which is defined by a nonlinear function containing a driving substrate concentration and parameters representing the capacity of the process and a substrate affinity constant. Most contemporary mechanism-based pharmacodynamic models are developed by integrating an appropriate drug exposure forcing function, a mathematical model of the interaction between the drug and its target (i.e., binding and transduction), and the physiological turnover (or production and loss) of the biomarker of drug response. Numerous complexities can be introduced to basic models, such as homeostatic feedback, tolerance mechanisms, disease progression, drug interactions, circadian rhythms, and many others. These basic and advanced models can be viewed as the groundwork for the development of comprehensive quantitative systems pharmacology models that are applicable across biological spatiotemporal scales.","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Glycosylation in Stem Cell Biology. 干细胞生物学中的糖基化。

Handbook of experimental pharmacology Pub Date : 2025-05-06 DOI: 10.1007/164_2025_748

Chika Ogura, Shoko Nishihara

{"title":"Glycosylation in Stem Cell Biology.","authors":"Chika Ogura, Shoko Nishihara","doi":"10.1007/164_2025_748","DOIUrl":"https://doi.org/10.1007/164_2025_748","url":null,"abstract":"Embryonic stem cells are pluripotent stem cells originally derived from the inner cell mass of blastocysts and have the essential characteristics of pluripotency and self-renewal. Pluripotent stem cells can differentiate into all of the cell types constituting the adult body. Our current understanding is that pluripotent stem cells transition through three stages: a naïve state, a formative state, and a primed state. The stemness and differentiation of pluripotent stem cells depend on cell-surface glycans, which work as essential modulators in ligand-receptor interactions, cell-cell interactions, and cell-extracellular matrix interactions. Cell-surface glycans bind to various signal ligands, including Wnt, fibroblast growth factors, and bone morphogenetic proteins, and are tissue-specific and developmentally regulated. In addition, intracellular O-linked N-acetylglucosamine, a modification found on only nuclear or cytoplasmic proteins, regulates core transcription factors involved in stemness, phosphorylation of downstream signal components, epigenetics, and liquid-liquid phase separation. Thus, various kinds of glycans regulate each stem cell status; furthermore, different glycan structures at each stage are simultaneously epigenetically regulated by the polycomb repressive complex PRC2. Understanding the functions of glycans in stemness and differentiation is increasingly important for both innovative clinical applications and basic research. This chapter focuses on the roles of glycans in mouse and human pluripotent stem cells.","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chemical Synthesis of Complex Carbohydrates. 复杂碳水化合物的化学合成。

Handbook of experimental pharmacology Pub Date : 2025-05-06 DOI: 10.1007/164_2025_747

Paul Kosma

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Advanced Mass Spectrometry Techniques for the Characterization of Carbohydrates. 表征碳水化合物的先进质谱技术。

Handbook of experimental pharmacology Pub Date : 2025-05-06 DOI: 10.1007/164_2025_749

Niklas Geue, Caitlin Walton-Doyle, Eleonora Renzi, Mathew Bejoy, Kevin Pagel

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Decrypting Glycosaminoglycan "sulfation code" with Computational Approaches. 用计算方法解密糖胺聚糖 "硫化密码"。

Handbook of experimental pharmacology Pub Date : 2025-04-02 DOI: 10.1007/164_2025_741

Sergey A Samsonov, Mateusz P Marcisz

{"title":"Decrypting Glycosaminoglycan \"sulfation code\" with Computational Approaches.","authors":"Sergey A Samsonov, Mateusz P Marcisz","doi":"10.1007/164_2025_741","DOIUrl":"https://doi.org/10.1007/164_2025_741","url":null,"abstract":"Glycosaminoglycans (GAGs), linear anionic periodic polysaccharides, play pivotal roles in various biologically relevant processes within the extracellular matrix (ECM). These processes encompass cell development, proliferation, signaling, ECM assembly, coagulation, and angiogenesis. GAGs perform their functions through their interactions with specific protein partners, rendering them attractive targets for regenerative medicine and drug design. However, the molecular mechanisms governing protein-GAG interactions remain unclear. Classical structure determination techniques face significant challenges when dealing with protein-GAG complexes. This is due to GAGs' unique properties, including their extensive length, flexibility, periodicity, symmetry, multipose binding, and the high heterogeneity of their sulfation patterns constituting the \"sulfation code.\" Consequently, only a limited number of experimental protein-GAG structures have been elucidated. Hence, theoretical approaches are particularly promising in deciphering the code for understanding the structure-function relationship of these complex molecules. In this chapter, we focus on the particularities, challenges, and advances of computational methods such as molecular docking, molecular dynamics, and free-energy calculations when applied to GAG-containing systems. These computational approaches offer valuable insights into the enigmatic world of protein-GAG interactions, paving the way for their enhanced understanding and potential therapeutic applications.","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Diagnostic and Therapeutic Approaches in Congenital Disorders of Glycosylation. 先天性糖基化疾病的诊断和治疗方法。

Handbook of experimental pharmacology Pub Date : 2025-03-22 DOI: 10.1007/164_2025_745

Alexandre Raynor, Élodie Lebredonchel, François Foulquier, François Fenaille, Arnaud Bruneel

{"title":"Diagnostic and Therapeutic Approaches in Congenital Disorders of Glycosylation.","authors":"Alexandre Raynor, Élodie Lebredonchel, François Foulquier, François Fenaille, Arnaud Bruneel","doi":"10.1007/164_2025_745","DOIUrl":"https://doi.org/10.1007/164_2025_745","url":null,"abstract":"Congenital disorders of glycosylation (CDG) constitute an increasing group of inborn metabolic disorders, with more than 170 described diseases to date. A disturbed glycosylation process characterizes them, with molecular defects localized in distinct cell compartments. In CDG, N-glycosylation, O-glycosylation, glycosylation of lipids (including phosphatidylinositol) as well as the glycosaminoglycan synthesis can be affected. Owing to the importance of glycosylation for the function of concerned proteins and lipids, glycosylation defects have diverse clinical consequences. CDG affected individuals often present with a non-specific multivisceral syndrome including neurological involvement, intellectual disability, dysmorphia, and hepatopathy. As CDG are rare diseases frequently lacking distinctive symptoms, biochemical and genetic testing bear important and complementary diagnostic roles.After an introduction on glycosylation and CDG, we review current biomarkers and analytical techniques in the field. Furthermore, we illustrate their interests in the follow-up of proven therapeutic approaches including D-mannose in MPI-CDG, D-galactose in PGM1-CDG, and manganese (MnSO4) in TMEM165-CDG.","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Integrating QSP and ML to Facilitate Drug Development and Personalized Medicine. 整合QSP和ML促进药物开发和个性化医疗。

Handbook of experimental pharmacology Pub Date : 2025-03-22 DOI: 10.1007/164_2024_740

Tongli Zhang

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Activity-Based Profiling of Retaining Glycosidases in Disease Diagnosis and Their Application in Drug Discovery. 保留糖苷酶在疾病诊断中的活性分析及其在药物开发中的应用。

Handbook of experimental pharmacology Pub Date : 2025-03-22 DOI: 10.1007/164_2025_743

Yevhenii Radchenko, Johannes M F G Aerts, Gideon J Davies, Jeroen D C Codée, Herman S Overkleeft

{"title":"Activity-Based Profiling of Retaining Glycosidases in Disease Diagnosis and Their Application in Drug Discovery.","authors":"Yevhenii Radchenko, Johannes M F G Aerts, Gideon J Davies, Jeroen D C Codée, Herman S Overkleeft","doi":"10.1007/164_2025_743","DOIUrl":"https://doi.org/10.1007/164_2025_743","url":null,"abstract":"Retaining glycosidases employ a two-step double displacement mechanism to hydrolyze their substrate glycosides. This mechanism involves a covalent enzyme-substrate adduct, and irreversible retaining glycosidase inhibitors have been designed based on this mechanism. Tagging such inhibitors with a reported moiety (biotin, fluorophore, bioorthogonal tag) provides activity-based retaining glycosidase probes. This chapter describes research on such activity-based probes that are inspired by the natural product retaining β-glucosidase inhibitor, cyclophellitol. Modulation of the configuration and substitution pattern yielded a suite of probes with which a host of retaining glycosidases are inhibited, and reported on, including enzymes involved in human pathologies (cancer, inherited lysosomal storage disorders). This chapter provides insights into their design and synthesis, their application in disease diagnosis, and their application in drug discovery, both as tools to uncover competitive inhibitors and as starting point for the design of covalent inhibitors.","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0