... understanding life in molecular detail

Dr Paul Ko Ferrigno

Paul Ko Ferrigno was an academic group leader until 2011 when he left to join Avacta (see http://www.avactalifesciences.com/person/paul-ko-ferrigno/ ).  He is currently a visiting member of the Centre.

Current major projects include:

Peptide aptamers are engineered proteins similar to antibodies that retain their integrity within cells. Peptides are genetically inserted into the primary sequence of a simple, stable scaffold protein. The folding of the scaffold conformationally constrains the peptide, so peptide aptamers bind partners with high specificity and affinity (1).

 

Using standard methods in genetic engineering, creating large libraries of random peptide aptamers is relatively easy. These libraries are screened, usually by yeast two hybrid methods, for binding to a target protein of interest. Peptide aptamer-encoding genes are sub-cloned into vectors which direct their expression in human or mouse cells, with the idea being that intracellular binding of a peptide aptamer to a target protein will interfere with its function, either by destabilising it or by binding to a surface normally used for a specific interaction. Any resulting phenotype yields insights into the molecular biology of the target protein (2). Where a peptide aptamer inhibits a cell-based model of disease, the peptide aptamer becomes a guide in drug discovery, whether by in silico methods or by drug displacement screens.

Peptide aptamers may also be used as a binding moiety in the construction of artificial proteins to study the target protein (reviewed in 3). Peptide aptamers may also be useful in diagnostics. For example, we have recently shown that peptide aptamer microarrays can specifically detect human papilloma virus proteins in infected cells. In collaboration with physicists, chemists and engineers we are using electrical detection of protein-peptide aptamer interactions that may lead to low-cost, disposable biochips for early detection of disease, detection of new biomarkers and population-wide health monitoring.

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Peptide aptamers are engineered proteins similar to antibodies that retain their integrity within cells. Peptides are genetically inserted into the primary sequence of a simple, stable scaffold protein. The folding of the scaffold conformationally constrains the peptide, so peptide aptamers bind partners with high specificity and affinity (1).

Using standard methods in genetic engineering, creating large libraries of random peptide aptamers is relatively easy. These libraries are screened, usually by yeast two hybrid methods, for binding to a target protein of interest. Peptide aptamer-encoding genes are sub-cloned into vectors which direct their expression in human or mouse cells, with the idea being that intracellular binding of a peptide aptamer to a target protein will interfere with its function, either by destabilising it or by binding to a surface normally used for a specific interaction. Any resulting phenotype yields insights into the molecular biology of the target protein (2). Where a peptide aptamer inhibits a cell-based model of disease, the peptide aptamer becomes a guide in drug discovery, whether by in silico methods or by drug displacement screens.

Peptide aptamers may also be used as a binding moiety in the construction of artificial proteins to study the target protein (reviewed in 3). Peptide aptamers may also be useful in diagnostics. For example, we have recently shown that peptide aptamer microarrays can specifically detect human papilloma virus proteins in infected cells. In collaboration with physicists, chemists and engineers we are using electrical detection of protein-peptide aptamer interactions that may lead to low-cost, disposable biochips for early detection of disease, detection of new biomarkers and population-wide health monitoring.

Detailed research programme                  Close ▲