Journal Article
Science, vol. 358, iss. 6369, pp. 1461-1466, 2017
Authors
Parisa Hosseinzadeh, Gaurav Bhardwaj, Vikram Khipple Mulligan, Matthew D. Shortridge, Timothy W. Craven, Fátima Pardo-Avila, Stephen A. Rettie, David E. Kim, Daniel-Adriano Silva, Yehia M. Ibrahim, Ian K. Webb, John R. Cort, Joshua N. Adkins, Gabriele Varani, David Baker
Abstract
Macrocycles by design
Macrocyclic peptides have diverse properties, including antibiotic and anticancer activities. This makes them good therapeutic leads, but screening libraries only cover a fraction of the sequence space available to peptides comprising D and L amino acids. Hosseinzadeh
et al.
achieved near-complete coverage in sampling the sequence space for 7- to 10-residue cyclic peptides and identified more than 200 designs predicted to fold into stable structures. Of 12 structures determined, nine were close to the computational models. They also sampled and designed 11- to 14-residue macrocycles, but without complete coverage. The designed macrocycles provide a path forward for engineering new therapeutics.
Science
, this issue p.
1461
