The Value of Peptides as a Therapeutic Agent
Challenging therapeutic areas such as the disruption of protein:protein interactions require molecules whose size occupies the space between the small molecule and large complex molecules. Peptide macrocycles potentially allow us to attain the high affinity and specificity found in antibodies and harness these features with the cellular permeability of small molecules. Gaining access to unique and high valued engineered peptide modalities is a major trend in the pharmaceutical industry.
The Peptide Engineering Programme seeks to enable technologies to advance peptide therapeutics, and to nucleate Singapore’s peptide-related research for innovative solutions. This is done through developing novel synthetic chemical methods in unison with peptide display technologies, which harness the diversity inherent in biological systems. This efficiently samples the macrocyclic chemical space in order to discover new pharmacologically attractive compounds.
Services & Capabilities
Track 1 — Diversity Oriented Technologies (DOTs) Impacting Target Diversity
Development of DOTs to increase unique chemical matter diver- sity through the use of biology as a key driver.
- DNA encoded libraries
- Phage display technology
- Yeast display technologies
Track 2 - Fast Synthesis Technologies (FST) Impacting lead optimization and manufacturing
Exploration of new synthesis technologies to enable quick and efficient synthesis of peptides. Our capabilities include micro- wave synthesis, and enzymatic synthesis of long peptides.
Associated services include:
- Incorporation of a-methylation and other unnatural amino acids
- Enzymatic syntehesis processs
- Peptide design and evaluation (linear and macrocycles)
- Peptoids, isoacyl / stapled / stitched peptides
- Structure stabilisation (a-helix / b sheet)
- C-terminal substituted amides
- Analysis of fractions
- Computational design and in-progress informatics
Track 3 - Formulation and Delivery Technologies (FDT) Impacting Manufacturing and Delivery
Exploration of fundamental biophysical and structure-property- activities of unique formulations for peptides. Assessment of large variety of systems to enable delivery of novel peptide modalities into cells e.g. receptor recognition motifs.
Peptide Conjugation & Targeting
- Fluorescent labeling
- Cysteine cross-linkage
- New conjugation chemistries
Peptide hit engineering
- Mini-body development
- Affinity maturation
- Scaffold grafting approaches
Strategically focused research
- Novel peptidomimetics
- C-terminal modifications
Biological target interrogation / validation assays
Toxicity and specificity screening
Computational chemistry, rational design, and SAR analysis
The programme team consists of top-notch scientists from the p53Lab, ICES (Institute of Chemical & Engineering Sciences) and Bioinformatics Institute (BII), A*STAR.
Fernando FERRER, Yuri FROSI, Shimin JIANG, Daniel LUKAMTO, Tsz Ying YUEN, Shilpa YADDAHALLI, Srinivasaraghavan KANNAN, Aronica PIETRO
Research Officers & Engineers
KOH Li Quan, Siti Radhiah RAMLAN, Bernadette LEE, Charmaine POH, Eunice HUI, LIEW Xi, Jing Yong NEO, Athur LIT, Yi Wee LIM
The PEP is supported by a Health & Biomedical Sciences domain Industry Alignment Fund-Prepositioning fund (A*STAR, EDB, NRF)
Library generation and screening against novel targets
- Hit-to-lead oncology project targeting two protein: protein interactions.
Principal Investigator - Charles JOHANNES
Principal Scientist p53Lab, A*STAR
Programme Manager (Admin) - Zhaoru LIN
Industry & Scientific Affairs Project Manager, p53Lab, A*STAR
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