Towards the Development of Antitumor Vaccines: A Synthetic Conjugate of a Tumor-Associated MUC1 Glycopeptide Antigen and a Tetanus Toxin Epitope

Keil, Stefanie; Claus, Christine; Dippold, Wolfgang; Kunz, Horst

doi:10.1002/1521-3773(20010119)40:2<366::aid-anie366>3.0.co;2-j

Cited by 121 publications

(74 citation statements)

References 27 publications

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“…For the attachment of this glycosylated amino acid, the coupling time was considerably extended in comparison to the unmodified amino acids due to the sterically demanding nature of the building block. After the completed synthesis, Fmoc-removal furnished the resinbound sialyl-T N glycododecapeptide (34) [148]. Parallel to this, the protected tetanus toxin peptide-spacer conjugate (35) was prepared on the solid phase.…”

Section: Synthesis Of Muc1 Glycopeptide Vaccine Conjugates For Selectmentioning

confidence: 58%

“…The limited success to induce cytotoxic lymphocyte proliferation in cell cultures after stimulation with short glycopeptide antigens led to the development of a novel concept for the construction of synthetic anti-tumor vaccines based on the cancer-associated MUC1 [148]. According to this novel approach, a tumor-associated the sialyl-T Nglycododecapeptide from MUC1 containing the peptide motif PDTRP as the immunodominant domain [181] was covalently linked via a flexible spacer to a peptide sequence representing a partial structure from tetanus toxoid.…”

Section: Synthesis Of Muc1 Glycopeptide Vaccine Conjugates For Selectmentioning

confidence: 99%

“…Starting from Tentagel resin (38) equipped with Fmoc-proline via the acidlabile trityl linker [200,201], both target peptides (40) and (41) from MUC1 were assembled on the solid phase and equipped with an aminofunctionalized triethylene glycol spacer ((39), Fig. (16)) [106,148].…”

Section: Synthesis Of Muc1 Glycopeptide Vaccine Conjugates For Selectmentioning

confidence: 99%

“…. Synthesis of MUC1 glycododecapeptide-vaccine conjugate[148]. a) solid-phase glycopeptide synthesis, see text b) morpholine/DMF c) 1.…”

mentioning

confidence: 99%

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Synthetic Glycopeptides from the Mucin Family as Potential Tools in Cancer Immunotherapy

Becker¹,

Dziadek²,

Wittrock³

et al. 2006

CCDT

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Compared to glycoproteins of healthy cells, glycoproteins of tumor cells are often aberrantly glycosylated. Thus, glycopeptide fragments of surface glycoproteins of tumor cells are of interest as tumor-associated antigens for the distinction between normal and tumor cells. Cancer immunotherapy directed at selectively targeting these tumor-associated glycoprotein structure alterations--deficient glycosylation and, thus, exposure of peptide epitopes which are masked in normal cells--is considered a promising approach for the treatment of cancer. For this purpose, glycoproteins from the mucin family are of particular interest. Mucins belong to a class of heavily O-glycosylated, high-molecular weight glycoproteins present on the surface of many epithelial cells. The mucin core protein consists of numerous tandem repeats rich in serine, threonine and proline. In their tumor-associated forms, epithelial mucins carry cryptic saccharide structures such as T(N)-, T-, sialyl-T(N)- and sialyl-T antigens and more complex oligosaccharides (e.g. Lewis(y)). In contrast to glycoproteins isolated from natural sources, synthetic glycopeptides can be obtained in high purity and with exactly defined structure. In this review, methodologies for the synthesis of mucin-type glycopeptides containing complex tumor-associated antigen structures are described. Due to the low immunogenicity often exhibited by synthetic tumor-associated glycopeptide antigens, their conjugation to carrier proteins or suitable T-cell epitopes is essential for the development of anti-tumor vaccines. The results of immunological evaluations of synthetic (glyco)peptides and oligosaccharides are described. Some of these synthetic vaccines show promising activities inducing proliferation of T-cells and cytotoxic T-cell responses.

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Section: Synthesis Of Muc1 Glycopeptide Vaccine Conjugates For Selectmentioning

confidence: 58%

Section: Synthesis Of Muc1 Glycopeptide Vaccine Conjugates For Selectmentioning

confidence: 99%

Section: Synthesis Of Muc1 Glycopeptide Vaccine Conjugates For Selectmentioning

confidence: 99%

“…. Synthesis of MUC1 glycododecapeptide-vaccine conjugate[148]. a) solid-phase glycopeptide synthesis, see text b) morpholine/DMF c) 1.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Synthetic Glycopeptides from the Mucin Family as Potential Tools in Cancer Immunotherapy

Becker¹,

Dziadek²,

Wittrock³

et al. 2006

CCDT

Self Cite

View full text Add to dashboard Cite

show abstract

“…14.13) [49]. As tumor-associated glycopeptides derived from mucins should be associated to T-cell epitopes in order to induce a robust immune response, the authors next coupled them to T-cell peptide epitope TToxs (17) to stimulate a tumor-selective response [50].…”

Section: The Fully Synthetic Approachmentioning

confidence: 99%