Amino acids, fluorinated binding

Initial studies to characterize the behavior of fluorinated amino acids within coiled-coil systems were conducted independently by the Tirrell group at CalTech and the Kumar group at Tufts. Work focused on incorporation of tri-fluoroleucine and trifluorovaline into the well-characterized leucine zipper peptides that readily assemble into dimeric ensembles in order to act as DNA-binding elements within transcription factors. The yeast transcriptional factor GCN4 contains a 56-amino acid DNA-binding segment known... 

Other non-covalent interactions such as C=0 F-C type, between a fluorine atom and the carbonyl of an amino acid, may take place for the stabilisation of enzyme-inhibitor supramolecular structures [28,30]. It is why the 4-fluorophenyl group is an important motif for binding pocket, as shown by the enhancement of one order of magnitude of the K by introducing one fluorine atom on thrombin inhibitor (Fig. 5) [30],... 

Lipophilic lanthanide complexes of fluorinated 3-diketonate ligands were demonstrated to bind unprotected amino acids under neutral conditions. It is not clear whether amino acids are bound as anions or zwitterions. Chiral ligands 63-66 have been prepared and tested for extraction of amino acids from water into dichloromethane [84] (Table 7). NMR and CD spectroscopic... 

Figure 16.6 Modulation of cation-n interactions using fluorinated amino acids, (a) Structures of acetylcholine (ACh) and 5-hydroxytryptamine (5-HT). (b) Receptor activation (log[ECS0/ ECso(wt)]) vs. calculated gas phase cation-n binding ability. Data from references [76] and 1771.

Relaxation-related work on proteins and polypeptides makes typically use of H, and NMR. A couple of papers have dealt with measurements on in fluorine-labelled aminoacids incorporated into peptide stuctures. Shi and co-workers introduced, at some specific sites, an unnatural fluorine-containing aminoacid and a nitroxide spin-label into a multidomain protein known to exist in different conformations. Measurements of F PRE allowed to determine the conformation under different conditions. Suzuki et used another fluorine-containing amino acid, inserted into different parts of a membrane-active peptide, as a local dynamics probe. They measured F transverse relaxation to examine changes in the mobility in different regions of the peptide upon binding to a lipid bilayer. 

---