4.0 Article

α-1,4-Galactosyltransferase-catalyzed glycosylation of sugar and lipid modified Leu-enkephalins

Journal

JOURNAL OF MOLECULAR CATALYSIS B-ENZYMATIC
Volume 97, Issue -, Pages 196-202

Publisher

ELSEVIER
DOI: 10.1016/j.molcatb.2013.08.018

Keywords

Enzymatic synthesis; Glycopeptide; Leu-enkephalin; Galactosyltransferase; Glycosylation

Funding

  1. Australian Research Council [DP1092829]
  2. Professorial Research Fellowship [DP110100212]
  3. Australian Postdoctoral Fellowship [DP1092829]
  4. Australian Research Council [DP1092829] Funding Source: Australian Research Council

Ask authors/readers for more resources

Glycosylation of therapeutic peptides has been reported to improve delivery and targeting of various vaccines and drugs to specific cells/tissues. However, chemical synthesis of complex oligosaccharide derivatives via conventional methods can be challenging due to the need for several orthogonal hydroxyl group protections. Liposaccharyl galactosyltransferase C, a naturally occurring glycosyltransferase enzyme from Neisseria meningitidis, was found to have the ability to transfer a galactosyl moiety to glyco(lipo)peptides. An enzymatic glycosylation of Leu-enkephalin glyco(lipo)peptides was developed and optimized in this study in order to prepare pain regulating peptides with potentially improved central nervous system delivery. (C) 2013 Elsevier B.V. All rights reserved.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.0
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Article Microbiology

Repurposing Carbamazepine To Treat Gonococcal Infection in Women: Oral Delivery for Control of Epilepsy Generates Therapeutically Effective Levels in Vaginal Secretions

Lucy K. Shewell, Christopher J. Day, Xavier De Bisscop, Jennifer L. Edwards, Michael P. Jennings

Summary: Neisseria gonorrhoeae has developed resistance to previous antibiotics, necessitating the development of novel antimicrobials. Carbamazepine has been shown to block the interaction between gonococcal pili and human complement receptor 3, as well as effectively clear established gonococcal infections. Concentrations of carbamazepine in vaginal fluid from women taking the drug were found to be sufficient to significantly reduce the number of viable gonococci recovered from cervical cell infections. These findings support the further development of carbamazepine as a host-targeted therapy for gonococcal cervicitis.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2023)

Article Biochemistry & Molecular Biology

Serum Neu5Gc biomarkers are elevated in primary cutaneous melanoma

Lucy K. Shewell, Christopher J. Day, Tiana Hippolite, Xavier De Bisscop, James C. Paton, Adrienne W. Paton, Michael P. Jennings

Summary: Cutaneous melanoma is an aggressive and deadly type of skin cancer, and its prevalence is increasing worldwide. Currently, there are no serum biomarkers available for the early detection of cutaneous melanoma. However, researchers have developed a Neu5Gc-specific lectin called SubB2M, which can detect elevated levels of Neu5Gc-containing biomarkers in the serum of cancer patients. This discovery suggests that serum Neu5Gc-containing glycoconjugates can serve as novel biomarkers for cutaneous melanoma and contribute to its early diagnosis.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2023)

Article Microbiology

Adherence of Nontypeable Haemophilus influenzae to Cells and Substrates of the Airway Is Differentially Regulated by Individual ModA Phasevarions

Preeti Garai, John M. Atack, Brandon M. Wills, Michael P. Jennings, Lauren O. Bakaletz, Kenneth L. Brockman

Summary: This study investigated the role of ModA phasevarions in regulating the adherence of NTHi to specific host substrates in the respiratory tract. The findings suggest that NTHi adherence is substrate-specific and dependent on the ModA allele encoded, with adhesins Protein E and P4 playing a significant role. Understanding the substrate-specific regulation of NTHi adherence by ModA phasevarions can aid in the development of targeted vaccines and therapeutics against NTHi.

MICROBIOLOGY SPECTRUM (2023)

Article Chemistry, Medicinal

Anti-cocaine Vaccine Development: Where Are We Now and Where Are We Going?

Rachel J. J. Stephenson, Istvan Toth

Summary: Cocaine is a widely used illegal drug that has significant medical and social consequences. The lack of effective pharmacological treatments has led to the development of anti-cocaine vaccines. Despite years of research, no approved pharmacological treatments exist to help individuals overcome cocaine addiction or prevent relapse.

JOURNAL OF MEDICINAL CHEMISTRY (2023)

Article Biochemistry & Molecular Biology

Actinobacillus pleuropneumoniae encodes multiple phase-variable DNA methyltransferases that control distinct phasevarions

Nusrat Nahar, Greg Tram, Freda E-C Jen, Zachary N. Phillips, Lucy A. Weinert, Janine T. Bosse, Jafar S. Jabbari, Quentin Gouil, Mei R. M. Du, Matthew E. Ritchie, Rory Bowden, Paul R. Langford, Alexander W. Tucker, Michael P. Jennings, Conny Turni, Patrick J. Blackall, John M. Atack

Summary: Actinobacillus pleuropneumoniae, the causative agent of porcine pleuropneumonia, has been found to possess phase-variable regulons known as phasevarions, which lead to altered expression of multiple genes via epigenetic mechanisms. This variation is caused by the variable expression of DNA methyltransferases, resulting in methylation differences within the bacterial population. The identification of these phasevarions in A. pleuropneumoniae is important for the development of a subunit vaccine against this veterinary pathogen.

NUCLEIC ACIDS RESEARCH (2023)

Article Oncology

N-glycolylneuraminic acid as a carbohydrate cancer biomarker

Jing Wang, Lucy K. Shewell, Christopher J. Day, Michael P. Jennings

Summary: One form of abnormal glycosylation in human tumors is the expression of Neu5Gc, a type of acid. The enzyme responsible for producing Neu5Gc in mammals is believed to be inactive in humans. However, low levels of Neu5Gc have been found in healthy humans, indicating its acquisition from diet, such as red meat. Elevated levels of Neu5Gc have been consistently detected in cancer tissues, cells, and serum samples, suggesting its potential as a biomarker for cancer. This review examines the use of Neu5Gc-containing tumor glycoconjugates as cancer biomarkers for detection, monitoring, prognosis, and therapeutic targets.

TRANSLATIONAL ONCOLOGY (2023)

Article Instruments & Instrumentation

Recent advances in the delivery and applications of nonviral CRISPR/Cas9 gene editing

Frazer Sinclair, Anjuman A. Begum, Charles C. Dai, Istvan Toth, Peter M. Moyle

Summary: The CRISPR/Cas9 genome editing system is a groundbreaking technology that has revolutionized genome editing for therapeutic, diagnostic, and precision medicine applications. The safe and efficient delivery of the CRISPR/Cas9 system has been a critical challenge. Viral vectors have shown promise, but face limitations for clinical applications. Nonviral delivery vectors, such as lipid, polymer, peptides, and inorganic nanoparticle-based systems, have emerged as viable alternatives. This review discusses the molecular mechanisms of CRISPR/Cas9, current delivery strategies, approaches for reducing off-target editing, and future directions for clinical trials.

DRUG DELIVERY AND TRANSLATIONAL RESEARCH (2023)

Article Microbiology

New Perspectives on Escherichia coli Signal Peptidase I Substrate Specificity: Investigating Why the TasA Cleavage Site Is Incompatible with LepB Cleavage

Joanna E. Musik, Jessica Poole, Christopher J. Day, Thomas Haselhorst, Freda E. -C. Jen, Thomas Ve, Veronika Masic, Michael P. Jennings, Yaramah M. Zalucki

Summary: This study designed 11 peptides to mimic signal peptides that are inefficiently cleaved by LepB. The binding affinity and inhibitory potential of these peptides against LepB were assessed. It was found that the tryptophan residue in the signal peptide inhibited the cleavage of the peptide by LepB, and replacing this residue with alanine improved the cleavage efficiency.

MICROBIOLOGY SPECTRUM (2023)

Article Chemistry, Medicinal

Synthetic Anti-Cocaine Nanoaccine Successfully Prevents Cocaine-Induced Hyperlocomotion

Harrison Y. R. Madge, Suzy Alexander, Armira Azuar, Jiahui Zhang, Prashamsa Koirala, Thomas H. Burne, Istvan Toth, Rachel J. Stephenson

Summary: Researchers have developed a peptide-based anti-cocaine vaccine that can induce immune responses in mice, providing a platform for the development of effective anti-drug vaccines.

JOURNAL OF MEDICINAL CHEMISTRY (2023)

Review Biochemistry & Molecular Biology

The biosynthesis and role of phosphorylcholine in pathogenic and nonpathogenic bacteria

Yuan Zhang, Freda E. -C. Jen, Kate L. Fox, Jennifer L. Edwards, Michael P. Jennings

Summary: Phosphorylcholine (ChoP) is present in all life forms, including bacteria. Recent research has shown that ChoP modification and phase variation play a role in bacterial pathogenesis. However, the mechanisms of ChoP synthesis in some bacteria are still unclear. This review examines the recent developments in ChoP-modified proteins and glycolipids, as well as ChoP biosynthetic pathways, and discusses the role of ChoP in bacterial pathobiology and immune response modulation.

TRENDS IN MICROBIOLOGY (2023)

Article Chemistry, Medicinal

High-Frequency Changes in Pilin Glycosylation Patterns during Neisseria meningitidis Serogroup a Meningitis Outbreaks in the African Meningitis Belt

Freda E. -C. Jen, Jodie L. Abrahams, Benjamin L. Schulz, Araceli Lamelas, Gerd Pluschke, Michael P. Jennings

Summary: In the meningitis belt of sub-Saharan Africa, cyclic meningococcal epidemics coincide with clonal waves of Neisseria meningitidis. A whole-genome sequencing study with meningococcal isolates collected during outbreaks identified the pilin glycosylation (pgl) locus as a hotspot of recombination. The exchange of pgl genes in N. meningitidis results in variable glycosylation patterns of pilin and other surface glycoproteins. Investigating pilin glycosylation can shed light on bacterial adaptation and potential targets for therapies and vaccines.

ACS INFECTIOUS DISEASES (2023)

Article Microbiology

Analysis of Bacterial Phosphorylcholine-Related Genes Reveals an Association between Type-Specific Biosynthesis Pathways and Biomolecules Targeted for Phosphorylcholine Modification

Yuan Zhang, Freda E. -C. Jen, Jennifer L. L. Edwards, Michael P. P. Jennings

Summary: Phosphorylcholine (ChoP) modification on bacterial surface proteins and carbohydrates contributes to host mimicry and survival in the host. This study systematically analyzed bacterial genomes to identify the potential ChoP biosynthetic pathways, and found the association between specific pathways and the type of ChoP-modified surface factors.

MICROBIOLOGY SPECTRUM (2023)

Article Materials Science, Multidisciplinary

Confinement of Triple-Enzyme-Involved Antioxidant Cascade in Two-Dimensional Nanostructure

Adel Szerlauth, Arpad Varga, Tamara Madacsy, Daniel Sebok, Sahra Bashiri, Mariusz Skwarczynski, Istvan Toth, Jozsef Maleth, Istvan Szilagyi

Summary: Incorporation of antioxidant enzymes into nanostructures provides a highly efficient and robust biocatalytic system for scavenging reactive oxygen species. The immobilized enzymes effectively reduce intracellular oxidative stress and prevent DNA damage induced by hydrogen peroxide. These findings are important for designing complex nanostructures with multienzymatic antioxidant activities.

ACS MATERIALS LETTERS (2023)

Article Microbiology

Phasevarions in Haemophilus influenzae biogroup aegyptius control expression of multiple proteins

Greg Tram, Freda E. -C. Jen, Zachary N. Phillips, John F. Lancashire, Jamie Timms, Jessica Poole, Michael P. Jennings, John M. Atack

Summary: This study characterized the ModA phasevarion in H. influenzae biogroup aegyptius, finding ModA13 in non-BPF causing strains and ModA16 unique to BPF causing isolates. Phase variation of ModA13 and ModA16 resulted in genome-wide changes to DNA methylation, leading to altered protein expression. However, these changes did not affect serum resistance in H. influenzae biogroup aegyptius strains.

MICROBIOLOGY SPECTRUM (2023)

Article Microbiology

High-depth RNA-Seq data sets to investigate the differences in gene expression mediated by phasevarions in non-typeable Haemophilus influenzae

John M. Atack, Kenneth L. Brockman, Lauren O. Bakaletz, Michael P. Jennings

Summary: This study presents high-depth coverage RNA-Seq data from prototype NTHi strains 723 and R2866, which encode two of the most common phase-variable ModA alleles found in NTHi strains, ModA2 and ModA10.

MICROBIOLOGY RESOURCE ANNOUNCEMENTS (2023)

No Data Available