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Soft Template Mediated Peptide Crystallisation

Project description

Keeping peptides in line could enable powerful new therapeutics

Proteins are ubiquitous in the human body, serving a huge variety of critical functions. These include short- and long-distance signalling, transport, storage, and structural support. These large, complex molecules are made up of much smaller units called peptides. Harnessing these simpler yet powerful natural subunits holds great promise for therapeutics. However, their benefits over small molecule-based drugs are difficult to exploit given their flexible and changing conformations in solution and their short half-lives. This EU-funded ASPIRATION project aims to develop template-based strategies for crystallising peptides for increased product stability, bioavailability and improvements to manufacturability.

Objective

Peptides are recognised for being highly selective and efficacious signalling molecules that bind to the specific cell surface receptors or ion channel where they trigger intracellular effects. They are relatively safe compared to small molecule-based drugs and are well tolerated in the human body. Peptide therapeutics exhibits an excellent opportunity in the pharmaceutical industry as their target specificity is much better than small molecules drugs, while the production cost and complexity are lower than protein-based biopharmaceuticals. In the past decade, peptide therapeutics have gained a wide range of applications in medicine and biotechnology. Currently, there are more than 60 US Food and Drug Administration (FDA) approved peptides medicine on the market and this is expected to grow significantly with 140 peptide drugs in the clinical trials and more than 500 peptide drugs in pre-clinical phase. Despite several advantages of peptide drugs, poor physical and chemical stability, and a short circulating plasma half-life are major issues related to the peptide drugs. Furthermore, these issues could be easily resolved by determining and studying the crystal forms of the peptides. Crystalline peptide not only improves the physical and chemical stability of the peptides but also improves processability and reduces the production cost. This action aims to introduce a peptide crystallisation method based on a soft template strategy where peptide building blocks i.e. amino acids or other short peptides will act as templates for the crystallisation of peptide drugs. This will be a low cost and scalable approach for crystallising peptides and gaining insight into the structural determination of peptides. Also, an in-depth understanding of the thermodynamic and kinetic processes that drive the crystallization for a specific peptide is required before the critical process parameters can be altered to achieve control over nucleation and crystal growth.

Coordinator

IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
Net EU contribution
€ 224 933,76
Address
SOUTH KENSINGTON CAMPUS EXHIBITION ROAD
SW7 2AZ LONDON
United Kingdom

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Region
London Inner London — West Westminster
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 224 933,76