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Science 315 (5820): 1817-1822

Copyright © 2007 by the American Association for the Advancement of Science

Computational Design of Peptides That Target Transmembrane Helices

Hang Yin,1* Joanna S. Slusky,1* Bryan W. Berger,1 Robin S. Walters,1 Gaston Vilaire,2 Rustem I. Litvinov,3 James D. Lear,1 Gregory A. Caputo,1 Joel S. Bennett,2 William F. DeGrado1,4{dagger}

Abstract: A variety of methods exist for the design or selection of antibodies and other proteins that recognize the water-soluble regions of proteins; however, companion methods for targeting transmembrane (TM) regions are not available. Here, we describe a method for the computational design of peptides that target TM helices in a sequence-specific manner. To illustrate the method, peptides were designed that specifically recognize the TM helices of two closely related integrins ({alpha}IIbß3 and {alpha}vß3) in micelles, bacterial membranes, and mammalian cells. These data show that sequence-specific recognition of helices in TM proteins can be achieved through optimization of the geometric complementarity of the target-host complex.

1 Department of Biochemistry and Biophysics, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
2 Hematology-Oncology Division, Department of Medicine, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
3 Department of Cell and Developmental Biology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
4 Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: wdegrado{at}mail.med.upenn.edu


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