Macrocyclic FKBP51 Ligands Define a Transient Binding Mode with Enhanced Selectivity was written by Voll, Andreas M.;Meyners, Christian;Taubert, Martha C.;Bajaj, Thomas;Heymann, Tim;Merz, Stephanie;Charalampidou, Anna;Kolos, Juergen;Purder, Patrick L.;Geiger, Thomas M.;Wessig, Pablo;Gassen, Nils C.;Bracher, Andreas;Hausch, Felix. And the article was included in Angewandte Chemie, International Edition in 2021.Electric Literature of C21H21NO4 The following contents are mentioned in the article:
Subtype selectivity represents a challenge in many drug discovery campaigns. A typical example is the FK506 binding protein 51 (FKBP51), which has emerged as an attractive drug target. The most advanced FKBP51 ligands of the SAFit class are highly selective vs. FKBP52 but poorly discriminate against the homologs and off-targets FKBP12 and FKBP12.6. During a macrocyclization pilot study, we observed that many of these macrocyclic analogs have unanticipated and unprecedented preference for FKBP51 over FKBP12 and FKBP12.6. Structural studies revealed that these macrocycles bind with a new binding mode featuring a transient conformation, which is disfavored for the small FKBPs. Using a conformation-sensitive assay we show that this binding mode occurs in solution and is characteristic for this new class of compounds The discovered macrocycles are non-immunosuppressive, engage FKBP51 in cells, and block the cellular effect of FKBP51 on IKK伪. Our findings provide a new chem. scaffold for improved FKBP51 ligands and the structural basis for enhanced selectivity. This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5Electric Literature of C21H21NO4).
(S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5) belongs to piperidine derivatives. Piperidine and its derivatives have become increasingly popular in many synthetic schemes. Piperidine derivatives are being utilized in different ways as anticancer, antiviral, antimalarial, antimicrobial, antifungal, antihypertension, analgesic, anti-inflammatory, anti-Alzheimer, antipsychotic and/or anticoagulant agents.Electric Literature of C21H21NO4
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem