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The modular synthesis of a precision glycomacromolecule presenting α-1,2-mannobiose in a multivalent fashion as a high-mannose glycan mimetic/ligand for targeting C-type lectins. 

TIRP enables directgrafting-frompolymerization of proteins and enzymes under physiological conditions, maintaining their structure and function. By using cysteine thiols as initiators, polymers are site-selectively grafted from unmodified proteins. 

Controlledradicalpolymerizations(CRPs)areoneofthemost importantways toobtainuniform, definedmolecularweight polymerswith complex composition and architecture such as block copolymers. Anew controlledandlight-initiatedradicalpolymerizationis introducedthatmakes useofthiol initiatorsandanIr-photocatalyst.Differentreactionparametersare studiedfortheirimportanceinthecontrolledcharacteristicsofpolymerization, suchaslowdispersity,controlofmolecularweights,andstraightforwardaccess toblockcopolymers.Thelightcontrolfurthermoreallowsforsimpleswitching onandoffof thepolymerization.Weproposeamechanismfor theso-called thiol-induced, light-activated,controlledradicalpolymerization(TIRP),whichincludestheformationofdormantspeciesandtheir light-andcatalyst-dependentequilibriumwiththeactivepolymerchainend.TIRPenriches theportfolioof controlledandlightinitiatedpolymerizationmethodsby itsviabilityatmildconditions andthepossibility togrowpolymers froma largevarietyof readilyavailablethiols. 

Abstract Within this work, a new class of sequence‐defined heteromultivalent glycomacromolecules bearing lactose residues and nonglycosidic motifs for probing glycoconjugate recognition in carbohydrate recognition domain (CRD) of galectin‐3 is presented. Galectins, a family of β‐galactoside‐binding proteins, are known to play crucial roles in different signaling pathways involved in tumor biology. Thus, research has focused on the design and synthesis of galectin‐targeting ligands for use as diagnostic markers or potential therapeutics. Heteromultivalent precision glycomacromolecules have the potential to serve as ligands for galectins. In this work, multivalency and the introduction of nonglycosidic motifs bearing either neutral, amine, or sulfonated/sulfated groups are used to better understand binding in the galectin‐3 CRD. Enzyme‐linked immunosorbent assays and surface plasmon resonance studies are performed, revealing a positive impact of the sulfonated/sulfated nonglycosidic motifs on galectin‐3 binding but not on galectin‐1 binding. Selected compounds are then tested with galectin‐3 positive MCF 7 breast cancer cells using an in vitro would scratch assay. Preliminary results demonstrate a differential biological effect on MCF 7 cells with high galectin‐3 expression in comparison to an HEK 293 control with low galectin‐3 expression, indicating the potential for sulfonated/sulfated heteromultivalent glycomacromolecules to serve as preferential ligands for galectin‐3 targeting.