ABSTRACT
The Molecular Scaffold Concept ........................................................................... 110 Motivations for the Development of Nonantibody Scaffolds ................................ 112 Factors Governing Protein−Protein Interactions .................................................... 112 Design Considerations for New Scaffolds ............................................................. 113 Successful Scaffolds .............................................................................................. 114
Immunoglobulin-Like β-Sandwich ............................................................... 115 β-Barrel ......................................................................................................... 116 β-Sheet Surface ............................................................................................. 116 Single Loop ................................................................................................... 116 α-Helical Scaffolds ....................................................................................... 117 Repeat Proteins ............................................................................................. 117 Multidomain Scaffolds ................................................................................. 117 Recognition Interfaces at the Junction of Two Domains .............................. 118
Roles of Interface Topography ............................................................................... 118 Advances in Display Technologies ........................................................................ 119 Advances in Sequence Diversity Design ............................................................... 120 Applications ........................................................................................................... 122
Antibody Alternatives ................................................................................... 122 Therapeutics .................................................................................................. 122 Afnity Purication ...................................................................................... 123 Crystallization Chaperones ........................................................................... 123 Intracellular Applications ..............................................................................124
Conclusions ............................................................................................................124 Acknowledgments .................................................................................................. 125 References .............................................................................................................. 125
Highly specic molecular recognition is one of the fundamental functions of proteins. In an effort to explore and exploit this functionality, intense efforts have been concentrated on the development of molecular systems that consistently produce novel proteins for molecular recognition. It is important to note that the goal of these efforts is to design molecular systems for diverse applications, and thus they should be clearly distinguished from traditional research and development efforts for a single, specic function. The use of the term design in the title of this chapter is deliberate with a purpose to emphasize this viewpoint. While traditional approaches have relied on natural systems, such as molecules involved in adaptive immunity as the source of interface diversity, recent advances in protein engineering technologies and also in our understanding of the principles governing molecular recognition by proteins have made it possible to create novel molecular recognition sites on other proteins.
