Human Lectins, Their Carbohydrate Affinities and Where to Find Them

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Human Lectins, Their Carbohydrate Affinities and Where to Find Them biomolecules Review Human Lectins, Their Carbohydrate Affinities and Where to Review HumanFind Them Lectins, Their Carbohydrate Affinities and Where to FindCláudia ThemD. Raposo 1,*, André B. Canelas 2 and M. Teresa Barros 1 1, 2 1 Cláudia D. Raposo * , Andr1 é LAQVB. Canelas‐Requimte,and Department M. Teresa of Chemistry, Barros NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829‐516 Caparica, Portugal; [email protected] 12 GlanbiaLAQV-Requimte,‐AgriChemWhey, Department Lisheen of Chemistry, Mine, Killoran, NOVA Moyne, School E41 of ScienceR622 Co. and Tipperary, Technology, Ireland; canelas‐ [email protected] NOVA de Lisboa, 2829-516 Caparica, Portugal; [email protected] 2* Correspondence:Glanbia-AgriChemWhey, [email protected]; Lisheen Mine, Tel.: Killoran, +351‐212948550 Moyne, E41 R622 Tipperary, Ireland; [email protected] * Correspondence: [email protected]; Tel.: +351-212948550 Abstract: Lectins are a class of proteins responsible for several biological roles such as cell‐cell in‐ Abstract:teractions,Lectins signaling are pathways, a class of and proteins several responsible innate immune for several responses biological against roles pathogens. such as Since cell-cell lec‐ interactions,tins are able signalingto bind to pathways, carbohydrates, and several they can innate be a immuneviable target responses for targeted against drug pathogens. delivery Since sys‐ lectinstems. In are fact, able several to bind lectins to carbohydrates, were approved they by canFood be and a viable Drug targetAdministration for targeted for drugthat purpose. delivery systems.Information In fact, about several specific lectins carbohydrate were approved recognition by Food by andlectin Drug receptors Administration was gathered for that herein, purpose. plus Informationthe specific organs about specific where those carbohydrate lectins can recognition be found by within lectin the receptors human was body. gathered herein, plus the specific organs where those lectins can be found within the human body. Keywords: human lectins; carbohydrate specific recognition; biological applications; targeted drug Keywords:delivery systems;human protein lectins; expression carbohydrate specific recognition; biological applications; targeted drug delivery systems; protein expression Citation: Raposo, C.D.; Canelas, 1.1. IntroductionIntroduction A.B.; Barros, M.T. Human Lectins, Lectins are an attractive class of proteins of non-immune origin that can either be Their Carbohydrate Affinities and Lectins are an attractive class of proteins of non‐immune origin that can either be free or linked to cell surfaces, and are involved in numerous biological processes, such as Where to Find Them. Biomolecules free or linked to cell surfaces, and are involved in numerous biological processes, such as Citation: Raposo, C.D.; Canelas, cell-cell interactions, signaling pathways, cell development, and immune responses [1]. 2021, 11, x. cell‐cell interactions, signaling pathways, cell development, and immune responses[1]. A.B.; Barros, M.T. Human Lectins, https://doi.org/10.3390/xxxxx LectinsLectins selectivelyselectively recognizerecognize carbohydratescarbohydrates andand reversiblyreversibly bindbind to them as long as the Their Carbohydrate Affinities and ligands are oriented in a specific manner. Some of the commonly occurring carbohydrates Where to Find Them. Biomolecules ligands are oriented in a specific manner. Some of the commonly occurring carbohydrates Academic Editors: Nuno Vale and that are found in Nature are D-fructose, D-galactose, L-arabinose, D-xylose, D-mannose, 2021, 11, 188. https://doi.org/ that are found in Nature are D‐fructose, D‐galactose, L‐arabinose, D‐xylose, D‐mannose, Vladimir N. Uversky D-glucose, D-glucosamine, D-galactosamine, L-fucose, various uronic acids, sialic acid, 10.3390/biom11020188 D‐glucose, D‐glucosamine, D‐galactosamine, L‐fucose, various uronic acids, sialic acid, and Received: 4 November 2020 andtheir their combinations combinations to form to other form di other‐ and oligosaccharides, di- and oligosaccharides, or other biomolecules or other biomolecules (Figure 1) Accepted: 26 January 2021 (Figure1)[2]. Academic Editors: Nuno Vale and [2]. Published: 29 January 2021 Vladimir N. Uversky Received: 4 November 2020 Publisher’s Note: MDPI stays neu‐ Accepted: 26 January 2021 tral with regard to jurisdictional Published: 29 January 2021 claims in published maps and insti‐ tutional affiliations. Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and FigureFigure 1. 1. StructuresStructures ofof thethe carbohydratecarbohydrate buildingbuilding blocksblocks foundfound inin Nature. Copyright:conditions of© the 2021 Creative by the Commons authors. Lectins in vertebrates can be classified either by their subcellular location, or by their LicenseeAttribution MDPI, (CC Basel, BY) Switzerland. license Lectins in vertebrates can be classified either by their subcellular location, or by their structure. Division based on their location includes integral lectins located in membranes This(http://creativecommons.org/licenses article is an open access article structure. Division based on their location includes integral lectins located in membranes distributed/by/4.0/). under the terms and asas structural structural components, components, or or soluble soluble lectins lectins present present in intra- in intra and‐ intercellularand intercellular fluids, fluids, which conditions of the Creative Commons can move freely. Attribution (CC BY) license (https:// Division according to lectin structure consists of several different types of lectins, such 2+ creativecommons.org/licenses/by/ as C-type lectins (binding is Ca dependent), I-type lectins (carbohydrate recognition do- 4.0/).Biomolecules 2021, 11, x. https://doi.org/10.3390/xxxxxmain is similar to immunoglobulins), galectin family (or S-type,www.mdpi.com/journal/biomolecules which are thiol dependent), Biomolecules 2021, 11, 188. https://doi.org/10.3390/biom11020188 https://www.mdpi.com/journal/biomolecules Biomolecules 2021, 11, x 2 of 22 Biomolecules 2021, 11, x 2 of 22 which can move freely. Biomolecules 2021, 11, 188 Division accordingwhich can to move lectin freely. structure consists of several different types of lectins,2 of 27 such as C‐type lectinsDivision (binding according is Ca2+ dependent), to lectin structure I‐type lectinsconsists (carbohydrate of several different recogni types‐ of lectins, tion domain is similarsuch as toC ‐immunoglobulins),type lectins (binding galectin is Ca2+ dependent),family (or S ‐Itype,‐type whichlectins are(carbohydrate thiol recogni‐ pentraxinsdependent), (pentameric pentraxinstion domain (pentameric lectins) is similar and P-typelectins) to immunoglobulins), lectinsand P‐ (specifictype lectins to galectin glycoproteins(specific family to glycoproteins (or containing S‐type, which are thiol mannosecontaining 6-phosphate) mannosedependent), 6‐ [phosphate)3]. pentraxins [3]. (pentameric lectins) and P‐type lectins (specific to glycoproteins Different lectins containing have have highmannose high similarity similarity 6‐ phosphate) in in the the residues residues [3]. that that bind bind to to saccharides, saccharides, most most of ofwhich which coordinate coordinate to metal toDifferent metal ions, ions, lectins and and water have water molecules.high molecules. similarity Nearly Nearly in theall animalresidues all animal lectins that lectins bindpossess possessto saccharides, sev‐ most of severaleral pockets pockets that thatwhich recognize recognize coordinate molecules molecules to metal other other ions, than than andcarbohydrates, water carbohydrates, molecules. meaning meaning Nearly that allthey that animal theyare mul lectins are‐ possess sev‐ multivalenttivalent and andcan eralpresent can pockets present 2 to that 12 2 to sitesrecognize 12 of sites interaction, ofmolecules interaction, allowing other allowing than the carbohydrates, binding the binding of several meaning of severalligands that they are mul‐ ligandssimultaneously. simultaneously. tivalentThe specificity and The can specificity and present affinity 2 and to of 12 affinitythe sites lectin of of ‐interaction,carbohydrate the lectin-carbohydrate allowing complex the depends binding complex onof several ligands dependsthe lectin, on which thesimultaneously. lectin, can be which very sensitive can The be specificity very to the sensitive structure and affinity to of the the of structure thecarbohydrate lectin of‐carbohydrate the (e.g., carbohydrate mannose complex depends on (e.g.,versus mannose glucose, versus theFigure lectin, glucose, 1), whichor Figureto canthe 1 beorientation), or very to the sensitive orientationof the to anomeric the of structure the anomericsubstituent of the substituent carbohydrate(α versus ( β α (e.g., mannose versusanomer,β anomer,e.g., in versusFigure e.g., in glucose,2), Figure or both. 2Figure), or Lectin both. 1), ‐or Lectin-carbohydratecarbohydrate to the orientation interactions interactionsof the are anomeric achieved are achieved substituent mainly (α versus β mainlythrough through hydrogenanomer, hydrogen bonds, e.g., van bonds, in der Figure Waals van der2), (steric or Waals both. interactions), (steric Lectin interactions),‐carbohydrate and hydrophobic andinteractions hydrophobic forces are (ex achieved‐ mainly forcesample
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