- 12:50 PM

Design and Characterization of Peptides That Target Transmembrane Helices

Bryan Berger1, Hubert Yin1, Joanna Slusky1, Greg Caputo1, Rustem Litvinov2, James Lear1, Joel Bennett3, and William DeGrado1. (1) Biochemistry and Biophysics, University of Pennsylvania School of Medicine, 1009 Stellar-Chance Laboratory, 36th & Hamilton Walk, Philadelphia, PA 19104, (2) Cell and Developmental Biology, University of Pennsylvania School of Medicine, BRB II/III, Philadelphia, PA 19104, (3) Hematology/Oncology Division, University of Pennsylvania School of Medicine, 924 BRB II/III, 421 Curie Drive, Philadelphia, PA 19104

Transmembrane (TM) helices play essential roles in biological processes such as signal transduction, solute transport and membrane protein folding and stability. In order to examine these processes in greater detail, we developed a computational method, CHAMP (computed anti-helical membrane protein), to design peptides which target the TM domains of membrane proteins in a sequence-specific manner. In particular, we designed peptides that target the TM domains of integrins αIIb and αν and demonstrate their specificity in bacterial membrane, platelets and micelles. Furthermore, using genetic selection methods, we are able to examine the specificity and affinity of interactions between the designed and target TM helices. Overall, our results indicate that TM peptides can be designed to selectively activate a given integrin TM domain as well as how a CHAMP methodology can be generalized to examine a wide range of TM-mediated processes.