Amino Acids

, Volume 49, Issue 11, pp 1867–1883 | Cite as

Targeting cancer-specific glycans by cyclic peptide lectinomimics

  • Maria C. Rodriguez
  • Austin B. Yongye
  • Mihael Cudic
  • Karina Martinez Mayorga
  • Enbo Liu
  • Barbara M. Mueller
  • Jon Ainsley
  • Tatyana Karabencheva-Christova
  • Christo Z. Christov
  • Mare CudicEmail author
  • Predrag CudicEmail author
Original Article


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.


Cyclic peptide Lectinomimics Carbohydrate-binding protein Glycosylation Tumor metastasis Cell migration 



Root-mean-square deviation


Aleuria aurantia lectin








Bovine serum albumin


Conditioned medium


Coefficient of variation






Dimethyl sulfoxide




Fluorescein isothiocyanate






Isothermal titration calorimetry


Matrix assisted laser desorption/ionization time-of-flight




Benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate


Reverse-phase high pressure liquid chromatography


Room temperature




Sambucus nigra lectin


Ulex europaeus I lectin


Solid-phase peptide synthesis


Trifluoroacetic acid, UV–Vis, ultraviolet–visible



We thank Dr. Anna Knapinska for providing tissue-culture expertise and Ms. Karen Gottwald for editing of the manuscript. This work was partly supported by the Florida Atlantic University [start-up funds to M.C.]; and the National Institutes of Health [National Institute on Drug Abuse (NIDA) RDA039722A to P.C. and National Cancer Institute (NCI) CA178754 to M.C.]. K.M.M. thanks Instituto de Química, UNAM for financing support.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest with the contents of this article.

Research involving human participants and/or animals

This article does not contain any studies with human participants or animals performed by any other authors.

Supplementary material

726_2017_2485_MOESM1_ESM.pdf (1.2 mb)
Supplementary material 1 (PDF 1248 kb)


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Copyright information

© Springer-Verlag GmbH Austria 2017

Authors and Affiliations

  • Maria C. Rodriguez
    • 1
  • Austin B. Yongye
    • 2
  • Mihael Cudic
    • 2
  • Karina Martinez Mayorga
    • 2
    • 3
  • Enbo Liu
    • 4
  • Barbara M. Mueller
    • 4
  • Jon Ainsley
    • 5
  • Tatyana Karabencheva-Christova
    • 6
  • Christo Z. Christov
    • 6
  • Mare Cudic
    • 1
    Email author
  • Predrag Cudic
    • 1
    Email author
  1. 1.Department of Chemistry and Biochemistry, Charles E. Schmidt College of ScienceFlorida Atlantic UniversityBoca RatonUSA
  2. 2.Torrey Pines Institute for Molecular StudiesPort Saint LucieUSA
  3. 3.Instituto de QuimicaUniversidad Nacional Autónoma de MéxicoMexicoMexico
  4. 4.San Diego Biomedical Research InstituteSan DiegoUSA
  5. 5.University of Northumbria at NewcastleNewcastle upon TyneUK
  6. 6.Michigan Technological UniversityHoughtonUSA

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