Targeting cancer-specific glycans by cyclic peptide lectinomimics
| Autor: | Mare Cudic, Enbo Liu, Tatyana G. Karabencheva-Christova, Austin B. Yongye, Karina Martinez Mayorga, Mihael Cudic, Jon Ainsley, Predrag Cudic, Maria C. Rodriguez, Barbara M. Mueller, Christo Z. Christov |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Glycosylation Odorrana grahami Lactams Cell Survival Protein Conformation Peptidomimetic Clinical Biochemistry Biology Binding Competitive Peptides Cyclic Biochemistry Article Aleuria aurantia Cell Line Inhibitory Concentration 50 Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound Drug Delivery Systems 0302 clinical medicine Protein structure Cell Movement Polysaccharides Lectins Neoplasms Humans Protein Interaction Domains and Motifs Fucose chemistry.chemical_classification Organic Chemistry Mucin Hep G2 Cells biology.organism_classification Cyclic peptide Molecular Docking Simulation 030104 developmental biology chemistry 030220 oncology & carcinogenesis MCF-7 Cells Lactam Peptidomimetics |
| Zdroj: | Amino Acids. 49:1867-1883 |
| ISSN: | 1438-2199 0939-4451 |
| Popis: | The transformation from normal to malignant phenotype in human cancers is associated with aberrant cell-surface glycosylation. Thus, targeting glycosylation changes in cancer is likely to provide not only better insight into the roles of carbohydrates in biological systems, but also facilitate the development of new molecular probes for bioanalytical and biomedical applications. In the reported study, we have synthesized lectinomimics based on odorranalectin 1; the smallest lectin-like cyclic peptide isolated from the frog Odorrana grahami skin, and assessed the ability of these peptides to bind specific carbohydrates on molecular and cellular levels. In addition, we have shown that the disulfide bond found in 1 can be replaced with a lactam bridge. However, the orientation of the lactam bridge, peptides 2 and 3, influenced cyclic peptide's conformation and thus these peptides' ability to bind carbohydrates. Naturally occurring 1 and its analog 3 that adopt similar conformation in water bind preferentially L-fucose, and to a lesser degree D-galactose and N-acetyl-D-galactosamine, typically found within the mucin O-glycan core structures. In cell-based assays, peptides 1 and 3 showed a similar binding profile to Aleuria aurantia lectin and these two peptides inhibited the migration of metastatic breast cancer cell lines in a Transwell assay. Altogether, the reported data demonstrate the feasibility of designing lectinomimics based on cyclic peptides. |
| Databáze: | OpenAIRE |
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