Carl T. Rollins

TL;DR: Ligands that bind specifically to a mutated FKBP over the wild-type protein are designed by remodeling an FK BP-ligand interface to introduce a specificity binding pocket and showed that recognition is surprisingly relaxed, with the modified ligand only partially filling the engineered cavity.

TL;DR: The results suggest that dimerization is a latent property of the FKBP fold: the crystal structure reveals a remarkably complementary interaction between the monomer binding sites, with only subtle changes in side-chain disposition accounting for the dramatic change in quaternary structure.

TL;DR: It is shown here that the FKBP12 ligand binding site is highly promiscuous-capable of binding a range of hydrophobic alkyl and aryl moieties with comparable affinity, and appears largely insensitive to the degree of occupancy or quality of packing of the pocket.

TL;DR: The total synthesis and in vitro activities of a series of chemical inducers of dimerization (CIDs) is described, and some congeners possess potency comparable to or better than the first generation natural product-derived CID, FK1012.

TL;DR: New synthetic chemical inducers of dimerization, comprising homodimeric FKBP ligands with engineered specificity for the designed point mutant F36V, have been evaluated for inducing targeted gene expression in mammalian cells and indicated that high-affinity dimerizers such as AP1903 are ineffective.