The Design of Peptides and Proteins Ranging from Hormones to Enzymes
Our efforts on the modelling and redesign of proteins have proceeded along two general routes. In one approach, the principal subject of this article, we have focussed on designing and building model peptides where we could neglect tertiary structure in at least the early phases of our work. For many peptides and proteins that bind in the amphiphilic environments of biological interfaces, complementary amphiphilic secondary structures are induced. We have developed design principles for the construction of model peptides which have illuminated the roles of secondary structures in the biological activity of apolipoproteins, peptide toxins and peptide hormones.
In the other approach to protein engineering that we have pursued, we have undertaken to redesign known tertiary structures by site-directed mutagenesis or by chemical modification. In the latter work we have introduced new covalently bound coenzyme analogs into proteins, giving rise to semisynthetic enzymes with novel catalytic activities.
Recently, we have embarked on a program of replacing secondary structural units in folded proteins of known tertiary structure by relatively non-homologous segments constructed employing design principles similar to those used in our amphiphilic peptide work. These studies represent a first step towards the design and construction of tertiary structure by the assembly of primary sequences.
KeywordsCholesterol Serine Proline Polystyrene Disulfide
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