Sequence‐Defined Heteromultivalent Precision Glycomacromolecules Bearing Sulfonated/Sulfated Nonglycosidic Moieties Preferentially Bind Galectin‐3 and Delay Wound Healing of a Galectin‐3 Positive Tumor Cell Line in an In Vitro Wound Scratch Assay

Freichel, Tanja; Heine, Viktoria; Laaf, Dominic; Mackintosh, Eleanor E.; Sarafova, Sophia D.; Elling, Lothar; Snyder, Nicole L.; Hartmann, Laura

doi:10.1002/mabi.202000163

Cited by 22 publications

(26 citation statements)

References 87 publications

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“…In addition to the screened or designed binding capability of SDPs, well-studied affinity ligands have also been incorporated into precise SDP scaffolds, providing another approach to create precision binding ligands. In this aspect, Hartmann and co-workers − developed a set of precise saccharide-conjugated polymers with binding affinities toward diverse lectins and proteins. For instance, an array of highly sulfated, glycomimetic precise oligomers and polydisperse polymers with different chain lengths were created, serving as potent inhibitors of viral binding/infection .…”

Section: Sdp-based Functional Biomaterialsmentioning

confidence: 99%

Sequence-Defined Synthetic Polymers for New-Generation Functional Biomaterials

Deng

Shi

Tan

et al. 2021

ACS Materials Lett.

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Synthetic polymers have been extensively exploited for biomedical and pharmacological applications, spanning from surgical devices, diagnostics, tissue engineering, regenerative medicine, to drug delivery systems. However, a fundamental and quantitative correlation between the primary chemical structures of polymeric biomaterials and the resulting biological responses remains elusive. Encouragingly, the advent and development of sequence-defined polymers (SDPs) provide an unprecedented opportunity to precisely tune their sequence information, intrachain folding, interchain self-assembly, and macroscopic properties, enabling the elucidation of the structure–property relationship of biomaterials. In this Perspective, we highlight recent advances of SDPs as next-generation functional biomaterials, and their potential applications in antimicrobial agents, bioactive ligands, precision drug delivery systems, bioimaging agents, and barcoded biomaterials, from sequence-defined synthetic oligomers and polymers. Finally, we present a critical outlook on the challenges in the design and development of SDP-based emergent biomaterials.

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Section: Sdp-based Functional Biomaterialsmentioning

confidence: 99%

Sequence-Defined Synthetic Polymers for New-Generation Functional Biomaterials

Deng

Shi

Tan

et al. 2021

ACS Materials Lett.

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“…For example, cyclodextrins, cyclic peptides, calixarenes and glycophanes have been designed from β-L [ 129 ]. Various lactosides and glycomimetics can be used to design high affinity and selective galectin antagonists, especially for human Gal-1 and Gal-3 which are largely studied [ 130 , 131 , 132 , 133 , 134 , 135 ]. Gal-3 is an attractive anticancer target, notably for breast and endometrial cancers [ 136 , 137 , 138 ].…”

Section: Tim-3/gal-9 Signaling Blockade With α/β-Lactosementioning

confidence: 99%

Modulation of the Gal-9/TIM-3 Immune Checkpoint with α-Lactose. Does Anomery of Lactose Matter?

Bailly

Thuru

Quesnel

2021

Cancers

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The disaccharide lactose is an excipient commonly used in pharmaceutical products. The two anomers, α- and β-lactose (α-L/β-L), differ by the orientation of the C-1 hydroxyl group on the glucose unit. In aqueous solution, a mutarotation process leads to an equilibrium of about 40% α-L and 60% β-L at room temperature. Beyond a pharmaceutical excipient in solid products, α-L has immuno-modulatory effects and functions as a major regulator of TIM-3/Gal-9 immune checkpoint, through direct binding to the β-galactoside-binding lectin galectin-9. The blockade of the co-inhibitory checkpoint TIM-3 expressed on T cells with anti-TIM-3 antibodies represents a promising approach to combat different onco-hematological diseases, in particular myelodysplastic syndromes and acute myeloid leukemia. In parallel, the discovery and development of anti-TIM-3 small molecule ligands is emerging, including peptides, RNA aptamers and a few specifically designed heterocyclic molecules. An alternative option consists of targeting the different ligands of TIM-3, notably Gal-9 recognized by α-lactose. Modulation of the TIM-3/Gal-9 checkpoint can be achieved with both α- and β-lactose. Moreover, lactose is a quasi-pan-galectin ligand, capable of modulating the functions of most of the 16 galectin molecules. The present review provides a complete analysis of the pharmaceutical and galectin-related biological functions of (α/β)-lactose. A focus is made on the capacity of lactose and Gal-9 to modulate both the TIM-3/Gal-9 and PD-1/PD-L1 immune checkpoints in oncology. Modulation of the TIM-3/Gal-9 checkpoint is a promising approach for the treatment of cancers and the role of lactose in this context is discussed. The review highlights the immuno-regulatory functions of lactose, and the benefit of the molecule well beyond its use as a pharmaceutical excipient.

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“…Moreover, pectin is considered a bioactive compound when ingested as a food component or as a dietary supplement, a topic that is explained in the next sections. It can be noted in Figure 3 the different Gal-3 forms available at biological environments, such as the monomeric unit (intra and extracellular) recently secreted present at initial interactions with natural ligands and pentameric (chimeric appearance) after associations of other monomeric units through their N-terminal domain due to ligand stimulus [ 18 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

The Complex Biological Effects of Pectin: Galectin-3 Targeting as Potential Human Health Improvement?

2022

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Galectin-3 is the only chimeric representative of the galectin family. Although galectin-3 has ubiquitous regulatory and physiological effects, there is a great number of pathological environments where galectin-3 cooperatively participates. Pectin is composed of different chemical structures, such as homogalacturonans, rhamnogalacturonans, and side chains. The study of pectin’s major structural aspects is fundamental to predicting the impact of pectin on human health, especially regarding distinct molecular modulation. One of the explored pectin’s biological activities is the possible galectin-3 protein regulation. The present review focuses on revealing the structure/function relationship of pectins, their fragments, and their biological effects. The discussion highlighted by this review shows different effects described within in vitro and in vivo experimental models, with interesting and sometimes contradictory results, especially regarding galectin-3 interaction. The review demonstrates that pectins are promissory food-derived molecules for different bioactive functions. However, galectin-3 inhibition by pectin had been stated in literature before, although it is not a fully understood, experimentally convincing, and commonly agreed issue. It is demonstrated that more studies focusing on structural analysis and its relation to the observed beneficial effects, as well as substantial propositions of cause and effect alongside robust data, are needed for different pectin molecules’ interactions with galectin-3.

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Sequence‐Defined Heteromultivalent Precision Glycomacromolecules Bearing Sulfonated/Sulfated Nonglycosidic Moieties Preferentially Bind Galectin‐3 and Delay Wound Healing of a Galectin‐3 Positive Tumor Cell Line in an In Vitro Wound Scratch Assay

Cited by 22 publications

References 87 publications

Sequence-Defined Synthetic Polymers for New-Generation Functional Biomaterials

Sequence-Defined Synthetic Polymers for New-Generation Functional Biomaterials

Modulation of the Gal-9/TIM-3 Immune Checkpoint with α-Lactose. Does Anomery of Lactose Matter?

The Complex Biological Effects of Pectin: Galectin-3 Targeting as Potential Human Health Improvement?

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