This virtual seminar series highlights the latest developments in peptide and protein science, reaching a diverse audience that includes peptide and protein chemists, carbohydrate chemists, and chemical biologists.
In June 2025, the researchers presenting will be
Dr Martin Fascione
Reader at the University of York
York Structural Biology Lab, Department of 浪花直播
https://www.york.ac.uk/chemistry/people/mfascione/
鈥淓xploring 鈲�-oxo aldehydes as uniquely reactive handles for (glyco)bioconjugation of proteins鈥�
The bioconjugation of proteins with small molecules has revolutionised the fields of chemical medicine, chemical biology, and cell biology, enabling scientists to probe and perturb dynamic cellular processes. The general use of chemical methods for the functionalisation of proteins is still limited however as they often require complicated reaction partners and/or non-physiological pH, which is incompatible with many protein scaffolds. In this lecture we will describe our work on exploring the unique reactivity of 鈲�-oxo aldehydes in bioconjugations under mild conditions, including their site-selective installation,1 reactivity in organocatalyst-mediated cross aldol reactions (OPAL)2,3 and application in the construction of neoglycoproteins4 for therapeutic applications including aggregation of adherent bacteria.5
References
and
Dr Annamaria Lilienkampf
Lecturer at the University of Edinburgh
https://edwebprofiles.ed.ac.uk/profile/dr-annamaria-lilienkampf
"MALDI-MS Based High-throughput Screening of Bacteria-binding Peptides from Combinatorial Peptide Libraries"
The time-consuming diagnosis of microbial infections has led to the misuse of antibiotics and the consequent rise in antibiotic resistance. There is therefore an urgent need for faster diagnostic methods and more effective drugs. Antimicrobial peptides (AMPs) are an alternative to small-molecule antibiotics but also hold promise for rapid identification of bacterial infections, e.g. via optical imaging. However, antibacterial activity of peptides does not necessarily correlate with strong binding, and most AMPs lack species selectivity, which are both crucial characteristics for diagnostics. Thus, there is a pressing need for peptides that bind strongly and selectively to specific bacterial species without cytotoxicity towards mammalian cells.
Screening of combinatorial peptide libraries is a powerful approach to identify peptides for biological targets. However, identifying and quantifying hits can be challenging, often requiring fluorescent labelling or specialised instrumentation. Matrix-assisted laser desorption ionisation mass spectrometry (MALDI-MS) is routinely used in the analysis of biomolecules, but its non-quantitative nature has limited its use in high-throughput screening. Here, we introduce an iodo-based mass defect peptide labelling strategy that allows quantification of peptides using high-resolution MALDI-FTICR MS. This labelling strategy was used to screen bacteria-binding peptides from glycine-zipper peptide libraries, identifying peptides that target Gram-positive and/or Gram-negative bacteria, with the screening results corroborated by fluorescent labelling of bacteria.
In June 2025, the researchers presenting will be
Dr Martin Fascione
Reader at the University of York
York Structural Biology Lab, Department of 浪花直播
https://www.york.ac.uk/chemistry/people/mfascione/
鈥淓xploring 鈲�-oxo aldehydes as uniquely reactive handles for (glyco)bioconjugation of proteins鈥�
The bioconjugation of proteins with small molecules has revolutionised the fields of chemical medicine, chemical biology, and cell biology, enabling scientists to probe and perturb dynamic cellular processes. The general use of chemical methods for the functionalisation of proteins is still limited however as they often require complicated reaction partners and/or non-physiological pH, which is incompatible with many protein scaffolds. In this lecture we will describe our work on exploring the unique reactivity of 鈲�-oxo aldehydes in bioconjugations under mild conditions, including their site-selective installation,1 reactivity in organocatalyst-mediated cross aldol reactions (OPAL)2,3 and application in the construction of neoglycoproteins4 for therapeutic applications including aggregation of adherent bacteria.5
References
- Chem. Commun. 2018, 54, 1501-1504.
- Chem. Sci. 2018, 9 (25), 5585-5593.
- ACS Chem. Biol., 2021, 16 (11), 2387-2400.
- Green Chem., 2022, 24, 8046-8053
- JACS Au, 2024, 4 (6), 2122-2129.
and
Dr Annamaria Lilienkampf
Lecturer at the University of Edinburgh
https://edwebprofiles.ed.ac.uk/profile/dr-annamaria-lilienkampf
"MALDI-MS Based High-throughput Screening of Bacteria-binding Peptides from Combinatorial Peptide Libraries"
The time-consuming diagnosis of microbial infections has led to the misuse of antibiotics and the consequent rise in antibiotic resistance. There is therefore an urgent need for faster diagnostic methods and more effective drugs. Antimicrobial peptides (AMPs) are an alternative to small-molecule antibiotics but also hold promise for rapid identification of bacterial infections, e.g. via optical imaging. However, antibacterial activity of peptides does not necessarily correlate with strong binding, and most AMPs lack species selectivity, which are both crucial characteristics for diagnostics. Thus, there is a pressing need for peptides that bind strongly and selectively to specific bacterial species without cytotoxicity towards mammalian cells.
Screening of combinatorial peptide libraries is a powerful approach to identify peptides for biological targets. However, identifying and quantifying hits can be challenging, often requiring fluorescent labelling or specialised instrumentation. Matrix-assisted laser desorption ionisation mass spectrometry (MALDI-MS) is routinely used in the analysis of biomolecules, but its non-quantitative nature has limited its use in high-throughput screening. Here, we introduce an iodo-based mass defect peptide labelling strategy that allows quantification of peptides using high-resolution MALDI-FTICR MS. This labelling strategy was used to screen bacteria-binding peptides from glycine-zipper peptide libraries, identifying peptides that target Gram-positive and/or Gram-negative bacteria, with the screening results corroborated by fluorescent labelling of bacteria.
