Evolving a Peptide: Library Platforms and Diversification Strategies

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 21(1), P. 215 - 215

Published: Dec. 27, 2019

Peptides are widely used in pharmaceutical industry as active ingredients, versatile tools drug discovery, and for delivery. They find themselves at the crossroads of small molecules proteins, possessing favorable tissue penetration capability to engage into specific high-affinity interactions with endogenous receptors. One commonly employed approaches peptide discovery design is screen combinatorial libraries, comprising a myriad variants either chemical or biological origin. In this review, we focus mainly on recombinant discussing different platforms their display expression, various diversification strategies library design. We take look well-established technologies well new developments future directions.

Language: Английский

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Snake three-finger α-neurotoxins and nicotinic acetylcholine receptors: molecules, mechanisms and medicine

Biochemical Pharmacology, Journal Year: 2020, Volume and Issue: 181, P. 114168 - 114168

Published: July 22, 2020

Language: Английский

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Immunosensors—The Future of Pathogen Real-Time Detection

Sensors, Journal Year: 2022, Volume and Issue: 22(24), P. 9757 - 9757

Published: Dec. 13, 2022

Pathogens and their toxins can cause various diseases of different severity. Some them may be fatal, therefore early diagnosis suitable treatment is essential. There are numerous available methods used for rapid screening. Conventional laboratory-based techniques such as culturing, enzyme-linked immunosorbent assay (ELISA) polymerase chain reaction (PCR) dominant. However, culturing still remains the “gold standard” identification. These have many advantages, including high sensitivity selectivity, but also limitations, long experiment-time, costly instrumentation, need well-qualified personnel to operate equipment. All these existing limitations reasons continuous search a new solutions in field bacteria For years, research has been focusing on use immunosensors types toxin- pathogen-detection. Compared conventional methods, do not require well-trained personnel. What more, quick, highly selective sensitive, possess potential significantly improve pathogen toxin diagnostic-processes. very important transport systems, where risk contamination by bioagents high. In this paper, advances immunosensor usage pathogenic microorganism- toxin-detection, described.

Language: Английский

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Medicinal Use of Chicory (Cichorium intybus L.)

Scientia Pharmaceutica, Journal Year: 2024, Volume and Issue: 92(2), P. 31 - 31

Published: June 5, 2024

The aim of this review is to discuss the numerous health-promoting properties Cichorium intybus L. and bring together a range publications broaden knowledge encourage further research consideration plant use as treatment for conditions. A comprehensive search articles in Polish English from 1986–2022 years was carried out PubMed, Google Scholar ScienceDirect using keywords chicory, L., sesquiterpene lactones their synonyms. Articles were checked titles, abstracts, full-text reviews. first part article discusses countries which it found, its life cycle or modern cultivation methods, well many uses, will be discussed more detail later article. increased interest plants medicines supplements also briefly mentioned, some limits that are associated with medical plants. In Results Discussion section, there discussion whole plant, collection all components, we then examine structure individual constituents Among these, those can utilized causal applications medicine, including polyphenols, mainly known anti-cancer properties, although, article, other discussed. examines inulin, major component Conclusions sections propose directions detailed factors may affect specific results, have safety implications when used medications.

Language: Английский

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Solenodon genome reveals convergent evolution of venom in eulipotyphlan mammals

Proceedings of the National Academy of Sciences, Journal Year: 2019, Volume and Issue: 116(51), P. 25745 - 25755

Published: Nov. 26, 2019

Venom systems are key adaptations that have evolved throughout the tree of life and typically facilitate predation or defense. Despite venoms being model for studying a variety evolutionary physiological processes, many taxonomic groups remain understudied, including venomous mammals. Within order Eulipotyphla, multiple shrew species solenodons oral venom systems. morphological variation their delivery systems, it remains unclear whether represents ancestral state in this group is result independent origins. We investigated origin evolution eulipotyphlans by characterizing system endangered Hispaniolan solenodon (Solenodon paradoxus). constructed genome to underpin proteomic identifications toxins, before undertaking analyses those constituents, functional assessments secreted venom. Our findings show consists paralogous kallikrein 1 (KLK1) serine proteases, which cause hypotensive effects vivo, seem likely vertebrate prey capture. Comparative provide convincing evidence shrews convergently, with 4 origins outnumbering all other find KLK1s been independently coopted into following divergence during late Cretaceous, suggesting constraints may be acting on these genes. Consequently, our represent striking example convergent molecular demonstrate distinct structural backgrounds can yield equivalent functions.

Language: Английский

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Anti-fungal properties and mechanisms of melittin

Applied Microbiology and Biotechnology, Journal Year: 2020, Volume and Issue: 104(15), P. 6513 - 6526

Published: June 4, 2020

Language: Английский

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Therapeutic Potential of Peptides Derived from Animal Venoms: Current Views and Emerging Drugs for Diabetes

Clinical Medicine Insights Endocrinology and Diabetes, Journal Year: 2021, Volume and Issue: 14

Published: Jan. 1, 2021

The therapeutic potential of venom-derived drugs is evident today. Currently, several significant are FDA approved for human use that descend directly from animal venom products, with others having undergone, or progressing through, clinical trials. In addition, there growing awareness the important cosmeceutical application products. success compounds linked to their increased bioactivity, specificity and stability when compared synthetically engineered compounds. This review highlights advancements in treatment diabetes related disorders. Exendin-4, originating saliva Gila monster lizard, represents proof-of-concept this drug discovery pathway diabetes. More recent evidence emphasises bees, cone snails, sea anemones, scorpions, snakes spiders effectively manage glycaemic control. Such could represent exciting exploitable scaffolds future diabetes, as well providing tools allow a better understanding cell signalling pathways insulin secretion metabolism.

Language: Английский

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Integration of organoids in peptide drug discovery: Rise of the high‐throughput screening

View, Journal Year: 2023, Volume and Issue: 4(6)

Published: July 3, 2023

Abstract Organoids are three‐dimensional cell aggregates with near‐physiologic behaviors and can undergo long‐term expansion in vitro. They amenable to high‐throughput drug screening processes, which renders them a viable preclinical model for development. The procedure of organoid‐based has been extensively employed discover small‐molecule drugs, encompassing the steps generating organoids, examining efficient drugs organoid cultures, data assessment. Compared small molecules, peptides more straightforward synthesize, be modified chemically, demonstrate high target specificity low cytotoxicity. Therefore, they have emerged as promising carriers deliver disease‐associated targets could therapeutic various diseases. To date, organoids used evaluate efficacy certain peptide agents; however, no reported. Given advantages there is an urgent need establish platforms. In this review, we discuss typical approach small‐molecular use well provide overview studies that incorporated research. Drawing on knowledge from molecular screens, explore difficulties potential avenues creating new platforms identify agents using models.

Language: Английский

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Therapeutic Applications of Aptamers

Published: May 22, 2024

Affinity reagents, or target-binding molecules, are quite versatile and major workhorses in molecular biology medicine. Antibodies the most famous frequently used type they have been for a wide range of applications, including laboratory techniques, diagnostics, therapeutics. However, antibodies not only available affinity reagents do significant drawbacks, laborious costly production. Aptamers one potential alternative that variety unique advantages. They single stranded DNA RNA molecules can be selected binding to many targets proteins, carbohydrates, small – which typically low affinity. There also cost-effective methods producing modifying nucleic acids vitro without cells, whereas require cells even whole animals. While there drawbacks using aptamers therapeutic vivo stability, had success clinical trials treating diseases two aptamer-based drugs gained FDA approval. Aptamer development is still ongoing, could lead additional applications aptamer therapeutics, antitoxins, combinatorial approaches with nanoparticles other acid therapeutics improve efficacy.

Language: Английский

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VISH-Pred: an ensemble of fine-tuned ESM models for protein toxicity prediction

Briefings in Bioinformatics, Journal Year: 2024, Volume and Issue: 25(4)

Published: May 23, 2024

Abstract Peptide- and protein-based therapeutics are becoming a promising treatment regimen for myriad diseases. Toxicity of proteins is the primary hurdle therapies. Thus, there an urgent need accurate in silico methods determining toxic to filter pool potential candidates. At same time, it imperative precisely identify non-toxic expand possibilities biologics. To address this challenge, we proposed ensemble framework, called VISH-Pred, comprising models built by fine-tuning ESM2 transformer on large, experimentally validated, curated dataset protein peptide toxicities. The steps VISH-Pred framework efficiently estimate toxicities taking just sequence as input, employing under sampling technique handle humongous class-imbalance data learning representations from fine-tuned language which then fed machine techniques such Lightgbm XGBoost. able correctly both peptides/proteins with toxicity proteins, achieving Matthews correlation coefficient 0.737, 0.716 0.322 F1-score 0.759, 0.696 0.713 three non-redundant blind tests, respectively, outperforming other over $10\%$ these quality metrics. Moreover, achieved best accuracy area receiver operating curve scores independent test sets, highlighting robustness generalization capability framework. By making available easy-to-use web server, expect serve valuable asset future endeavors aimed at discerning peptides enabling efficient therapeutics.

Language: Английский

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