Structure/activity studies of the anti‐MUC1 monoclonal antibody C595 and synthetic MUC1 mucin‐core‐related peptides and glycopeptides

Spencer, Dir; Missailidis, S.; Denton, G.; Murray, A.; Brady, K.; Matteis, Cristina I. De; Searle, M. S.; Tendler, Saul J. B.; Price, M. R.

doi:10.1002/(sici)1520-6343(1999)5:2<79::aid-bspy2>3.3.co;2-r

Cited by 4 publications

(6 citation statements)

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“…All glycosylated peptides showed distinctly decreased reactivity with mAb HMFG1, while monoglycosylation showed no effect and di-or triglycosylation enhanced the reactions with mAb C595 compared to the non-glycosylated peptide. Circular dichroism studies revealed that a lefthanded polyproline II helix adopted by this peptide in solution is further stabilized by addition of the GalNAc residues [55]. Another set of peptides and glycopeptides was used to study a large number of anti-MUC1 monoclonal antibodies recognizing peptidic epitopes in the same immunodominant MUC1 region [56,57].…”

Section: Effects Of Glycosylation On Peptidic Epitopes Of Glycoproteinssupporting

confidence: 61%

The role of glycosylation in protein antigenic properties

Lisowska¹

2002

Cellular and Molecular Life Sciences (CMLS)

101

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Glycosylation of proteins is a common event and contributes to protein antigenic properties. Most data have been obtained from model studies on glycoprotens with well-defined structure or synthetic glycopeptides and their respective monoclonal antibodies. Antibodies raised against glycoprotein antigens may be specific for their carbohydrate units which are recognized irrespective of the protein carrier (carbohydrate epitopes), or in the context of the adjacent amino acid residues (glycopeptidic epitopes). Conformation or proper exposure of peptidic epitopes of glycoproteins is also frequently modulated by glycosylation due to intramolecular carbohydrate-protein interactions. The effects of glycosylation are broad: glycosylation may 'inactivate' the peptidic epitope or may be required for its reactivity with the antibody, depending on the structure of the antigenic site and antibody fine specificity. Evidence is increasing that similar effects of glycosylation pertain to T cell-dependent cellular immune responses. Glycosylated peptides can be bound and presented by MHC class I or II molecules and elicit glycopeptide-specific T cell clones.

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Section: Effects Of Glycosylation On Peptidic Epitopes Of Glycoproteinssupporting

confidence: 61%

The role of glycosylation in protein antigenic properties

Lisowska¹

2002

Cellular and Molecular Life Sciences (CMLS)

101

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“…In simple structure-activity relationship studies, several Pro residues, including Pro9 in apidaecin, were found to be responsible for the antibacterial activity of the peptide [49,89]. Consecutive prolines in a sequence usually assume a lefthanded polyproline II helix structure, as was shown for the classical examples, the mucins [90]. Indeed, circular dichroism spectra of Bac-5 [63,91] and PR-39 [74] resemble that of polyproline II helices [92].…”

Section: Conformation and Role Of The Proline Residuesmentioning

confidence: 99%

“…Accordingly, no significant secondary structure was detected for the polyproline II helical mucin peptides by NMR [90] and, likewise, the predominantly unordered structure of drosocin as detected by NMR [95] may, but not necessarily, reflect the presence of an underlying polyproline II helix conformation. In support of this, energy calculations of Bac-5 suggest a structure more extended than that of a polyproline II helix [91].…”

Section: Conformation and Role Of The Proline Residuesmentioning

confidence: 99%

The short proline-rich antibacterial peptide family

Ötvös¹

2002

Cellular and Molecular Life Sciences (CMLS)

194

201

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From the many peptide families that are induced upon bacterial infection and can be isolated from all classes of animals, the short, proline-rich antibacterial peptides enjoy particular interest. These molecules were shown to inactivate an intracellular biopolymer in bacteria without destroying or remaining attached to the bacterial cell membrane, and as such emerged as viable candidates for the treatment of mammalian infections. These peptides were originally isolated from insects, they kill mostly gram-negative bacteria with high efficiency and they show structural similarities with longer insect- and mammal-derived antimicrobial peptides. However, while the distant relatives appear to carry multiple functional domains, apidaecin, drosocin, formaecin and pyrrhocoricin consist of only minimal determinants needed to penetrate across the cell membrane and bind to the target biopolymer. These peptides appear to inhibit metabolic processes, such as protein synthesis or chaperone-assisted protein folding. Pyrrhocoricin derivatives protect mice from experimental infections in vivo, suggesting the utility of modified analogs in the clinical setting. Sequence variations of the target protein at the peptide-binding site may allow the development of new peptide variants that kill currently unresponsive strains or species.

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“…Attachment of three GalNAc residues to a 25-mer mucin peptide is sufficient to increase both the population of peptides adopting a polyproline II (PPII) helix conformation and the binding of the monoclonal antibody C595. [234] A similar result was obtained by Karsten and co-workers who examined the binding of 28 Asp-Thr-Arg (DTR)-specific anti-MUC 1 antibodies to 12 synthetic MUC 1 20-and 21-mers containing T-and T N antigens at varying positions. [235] The DTR motif is a preferred target for the majority of the peptide-specific anti-MUC 1 antibodies.…”

Section: Chembiochem 2000 1 214 ± 246mentioning

confidence: 77%

“…[234] Fluorescence binding quenching studies with the monoclonal antibody C595, which recognises a Pro-Asp-Thr-Arg (PDTR) epitope, showed that the introduction of three GalNAc residues at threonines 9 and 21 and at serine 20 increased the MUC 1 peptide ± antibody association constant (150 versus 151, Figure 10). Interestingly, this increase appeared to coincide with a population increase of the PPII helix conformation as indicated by CD spectroscopy in cryogenic mixtures.…”

Section: Chembiochem 2000 1 214 ± 246mentioning

confidence: 97%

Glycopeptide Synthesis and the Effects of Glycosylation on Protein Structure and Activity

Seitz

2000

ChemBioChem

196

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Despite the omnipresence of protein glycosylation in nature, little is known about how the attachment of carbohydrates affects peptide and protein activity. One reason is the lack of a straightforward method to access biologically relevant glycopeptides and glycoproteins. The isolation of homogeneous glycopeptides from natural sources is complicated by the heterogeneity of naturally occuring glycoproteins. It is chemical and chemoenzymatic synthesis that is meeting the challenge to solve this availability problem, thus playing a key role for the advancement of glycobiology. The current art of glycopeptide synthesis, albeit far from being routine, has reached a level of maturity that allows for the access to homogeneous and pure material for biological and medicinal research. Even the ambitious goal of the total synthesis of an entire glycoprotein is within reach. It is demonstrated that with the help of synthetic glycopeptides the effects of glycosylation on protein structure and function can be studied in molecular detail. For example, in immunology, synthetic (tumour-specific) glycopeptides can be used as immunogens to elicit a tumour-cell-specific immune response. Again, synthetic glycopeptides are an invaluable tool to determine the fine specificity of the immune response that can be mediated by both carbohydrate-specific B and T cells. Furthermore, selected examples for the use of synthetic glycopeptides as ligands of carbohydrate-binding proteins and as enzyme substrates or inhibitors are presented.

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Structure/activity studies of the anti‐MUC1 monoclonal antibody C595 and synthetic MUC1 mucin‐core‐related peptides and glycopeptides

Cited by 4 publications

References 0 publications

The role of glycosylation in protein antigenic properties

The role of glycosylation in protein antigenic properties

The short proline-rich antibacterial peptide family

Glycopeptide Synthesis and the Effects of Glycosylation on Protein Structure and Activity

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