Lectin Ligands: New Insights into Their Conformations and Their Dynamic Behavior and the Discovery of Conformer Selection by Lectins

Lieth, C.W. von der; Siebert, Hans Christian; Kožár, Tibor; Burchert, Maria; Frank, Martin; Gilleron, Martine; Kaltner, Herbert; Kayser, Gian; Tajkhorshid, Emad; Bovin, Nicolai V.; Vliegenthart, Johannes F.G.; Gabius, Hans‐Joachim

doi:10.1159/000046452

Cited by 77 publications

(51 citation statements)

References 102 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lectins represent a family of proteins-each containing a subtype-specific carbohydrate recognition domain (CRD)-that are neither catalytic enzymes nor immunoglobulins. 247,248 Lectins that specifically bind b-galactosides are now termed galectins, having previously been known as S-type lectins. Galectins are thought to be involved with cell adhesion, migration, and survival.…”

Section: Figmentioning

confidence: 99%

Matricellular Proteins in the Trabecular Meshwork: Review and Update

Chatterjee

Villarreal

Rhee

2014

Journal of Ocular Pharmacology and Therapeutics

View full text Add to dashboard Cite

Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide, and intraocular pressure (IOP) is an important modifiable risk factor. IOP is a function of aqueous humor production and aqueous humor outflow, and it is thought that prolonged IOP elevation leads to optic nerve damage over time. Within the trabecular meshwork (TM), the eye's primary drainage system for aqueous humor, matricellular proteins generally allow cells to modulate their attachments with and alter the characteristics of their surrounding extracellular matrix (ECM). It is now well established that ECM turnover in the TM affects outflow facility, and matricellular proteins are emerging as significant players in IOP regulation. The formalized study of matricellular proteins in TM has gained increased attention. Secreted protein acidic and rich in cysteine (SPARC), myocilin, connective tissue growth factor (CTGF), and thrombospondin-1 and -2 (TSP-1 and -2) have been localized to the TM, and a growing body of evidence suggests that these matricellular proteins play an important role in IOP regulation and possibly the pathophysiology of POAG. As evidence continues to emerge, these proteins are now seen as potential therapeutic targets. Further study is warranted to assess their utility in treating glaucoma in humans.

show abstract

Section: Figmentioning

confidence: 99%

Matricellular Proteins in the Trabecular Meshwork: Review and Update

Chatterjee

Villarreal

Rhee

2014

Journal of Ocular Pharmacology and Therapeutics

View full text Add to dashboard Cite

show abstract

“…A hallmark of oligosaccharides, setting them apart from the highly flexible peptides, is their limited conformational space (von der Lieth et al, 1998). The bulky rings linked by glycosidic bonds can only be accommodated in few positions without clashes.…”

Section: The Third Dimension Of the Sugar Codementioning

confidence: 99%

From structural to functional glycomics: core substitutions as molecular switches for shape and lectin affinity of N-glycans

André

Kožár²,

Kojima³

et al. 2009

BCHM

View full text Add to dashboard Cite

Glycan epitopes of cellular glycoconjugates act as versatile biochemical signals (sugar coding). Here, we test the hypothesis that the common N-glycan modifications by core fucosylation and introduction of the bisecting Nacetylglucosamine moiety have long-range effects with functional consequences. Molecular dynamics simulations indicate a shift in conformational equilibria between linear extension or backfolding of the glycan antennae upon substitution. We also present a new fingerprint-like mode of presentation for this multi-parameter system. In order to delineate definite structure-function relationships, we strategically combined chemoenzymatic synthesis with bioassaying cell binding and the distribution of radioiodinated neoglycoproteins in vivo. Of clinical relevance, tailoring the core region affects serum clearance markedly, e.g., prolonging circulation time for the neoglycoprotein presenting the N-glycan with both substitutions. a2,3-Sialylation is another means toward this end, similarly seen for type II branching in triantennary N-glycans. This discovery signifies that rational glycoengineering along the given lines is an attractive perspective to optimize pharmacokinetic behavior of glycosylated pharmaproteins. Of general importance for the concept of the sugar code, the presented results teach the fundamental lesson that N-glycan core substitutions convey distinct characteristics to the concerned oligosaccharide relevant for cis and trans biorecognition processes. These modifications are thus molecular switches.

show abstract

“…Answers to some of these questions are presented here, but much work remains to be done, which also includes further aspects discussed in this issue, e.g. conformational aspects of the carbohydrate epitopes and the implications for histochemical localization [Danguy et al, 1998;von der Lieth et al, 1998]. …”

Section: Resultsmentioning

confidence: 99%

Cancer-Associated Glycosphingolipid Antigens: Their Structure, Organization, and Function

Hakomori

1998

Cells Tissues Organs

160

113

View full text Add to dashboard Cite

Experimental and human cancers are often characterized by the presence of tumor-associated glycosphingolipid (GSL) antigens defined by monoclonal antibodies. Major progress has been made during the past two decades on structural identification of these antigens. None of these structures are truly ‘tumor-specific’. However, many of the antibodies show preferential or ‘specific’ reactivity with tumors, based on organizational differences of membrane GSLs in tumor cells versus normal cells. Clustered GSL antigens organized with transducer molecules in microdomain have been found recently to comprise a structural and functional unit involved in tumor cell adhesion coupled with signal transduction. Some of the GSL antigens have been identified as adhesion molecules recognized by carbohydrate-binding proteins or by complementary carbohydrates on target cells. Such adhesion, coupled with signaling, may initiate the metastatic process. Elucidating the mechanism of this initial adhesion/signaling step may lead to discovery of therapeutic agents that disrupt adhesion (‘antiadhesion therapy’) or normalize signaling (‘ortho-signaling therapy’). Tumor-associated GSL antigens are also a target in immunotherapy of tumors, including development of antitumor vaccines.

show abstract

Lectin Ligands: New Insights into Their Conformations and Their Dynamic Behavior and the Discovery of Conformer Selection by Lectins

Cited by 77 publications

References 102 publications

Matricellular Proteins in the Trabecular Meshwork: Review and Update

Matricellular Proteins in the Trabecular Meshwork: Review and Update

From structural to functional glycomics: core substitutions as molecular switches for shape and lectin affinity of N-glycans

Cancer-Associated Glycosphingolipid Antigens: Their Structure, Organization, and Function

Contact Info

Product

Resources

About