DESIGN, SYNTHESIS, AND KINETIC EVALUATION OF HIGH-AFFINITY FKBP LIGANDS AND THE X-RAY CRYSTAL-STRUCTURES OF THEIR COMPLEXES WITH FKBP12

Authors
HOLT DA LUENGO JI YAMASHITA DS OH HJ KONIALIAN AL YEN HK ROZAMUS LW BRANDT M BOSSARD MJ LEVY MA EGGLESTON DS LIANG J SCHULTZ LW STOUT TJ CLARDY J
Citation
Da. Holt et al., DESIGN, SYNTHESIS, AND KINETIC EVALUATION OF HIGH-AFFINITY FKBP LIGANDS AND THE X-RAY CRYSTAL-STRUCTURES OF THEIR COMPLEXES WITH FKBP12, Journal of the American Chemical Society, 115(22), 1993, pp. 9925-9938
Citations number
67
Categorie Soggetti
Chemistry
Journal title
Journal of the American Chemical Society → ACNP
ISSN journal
00027863
Volume
115
Issue
22
Year of publication
1993
Pages
9925 - 9938
Database
ISI
SICI code
0002-7863(1993)115:22<9925:DSAKEO>2.0.ZU;2-S
Abstract
The design and synthesis of high-affinity FKBP12 ligands is described. These compounds potently inhibit the cis-trans-peptidylprolyl isomera se (rotamase) activity catalyzed by FKBP12 with inhibition constants ( K(i,app)) as low as 1 nM, yet they possess remarkable structural simpl icity relative to FK506 and rapamycin, from which they are conceptuall y derived. The atomic structures of three FKBP12-ligand complexes and of one unbound ligand were determined by X-ray crystallography and are compared to the FKBP12-FK506 and FKBP12-rapamycin complexes.