Ojima I. (ed.) Fluorine in Medicinal Chemistry and Chemical Biology

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Plate 16.2 Fluorous small-molecule microarrays. Small-molecule histone deacetylase

(HDAC) binders are noncovalently immobilized onto a glass slide coated with ﬂ uorocarbon

compounds. An antibody labeled with a ﬂ uorescent dye recognizes HDAC proteins.

(Source: Vegas, A. J., Brander, J. E., Tang, W. et al., Fluorous-based small-molecule microarrays

for the discovery of histone deacetylase inhibitors, Angew. Chem. Int. Ed. (2007), 46, 7960–

7964. Copyright Wiley-VCH Verlag GmbH & Co. KGaA. Reproduced with permission.)

Plate 16.3 The structure of apo-IFABP (PDB code: 1IFB). Eight Phe residues (shown in stick

representation), the D

–E and I–J regions, and location of G121 are indicated by labels. The

structure was generated using MacPyMOL (DeLano Scientiﬁ c LLC, Palo Alto, CA, U.S.A.).

Plate 16.4 Illustration of the S-state and T-state of the antimicrobial peptide PGLa in a DMPC

membrane. At low concentrations, PGLa adopts an S-state. At high concentrations, PGLa

assumes a tilted T-state. PGLa forms a dimer in the T-state (shown in purple).

(Source: Glaser, R. W., Sachse, C., Durr, U. H. N. et al., Concentration-dependent realignment

of the antimicrobial peptide PGLa in lipid membranes observed by solid-state F-19-NMR,

Biophys. J. (2005) 88, 3392–3397. Reproduced with permission from the Biophysical

Society.)

Plate 16.5 The dimer structure of PG-1 (PDB code: 1ZY6) in POPC bilayers as determined

by solid-state NMR. Isotopically labeled amino acids are shown in stick format; Phe12 was

labeled with

F, Cys12 with

N and

C, and Val16 with

C. Inter- and intramolecular dis-

tances were used to determine the relative position of the two monomers.

Plate 16.7 Fluorinated prolines in collagen. (a) The trans/cis isomerization of amide bonds

and main-chain angles of proline residues. The n → π* interaction, depicted by a dashed line,

helps stabilize backbone dihedral angles. (b) Electron-withdrawing groups at Cγ inﬂ uence the

ring conformation of proline residues through the “gauche effect.” The Cγ-endo pucker is

favored when R

= H and R

= F, OH, or H. The Cγ-exo pucker is favored when R

= OH or

F, and R

= H. Preorganization of the pyrrolidine ring contributes to the thermal stability of

collagen and mimics. Flp: R

= H and R

= F; ﬂ p: R

= F and R

= H; Hyp: R

= H and

= OH; hyp: R

= OH and R

= H. (c) Model structure of collagen (PDB code: 1CAG).

Three hydroxyprolines at Yaa positions from each peptide chain are shown in ball-and-stick

representation. Carbon = gray; Nitrogen = blue; Oxygen = red.

Plate 16.9 (a) Sequences of transmembrane peptides TH1, TF1, TH2, and TF2. Asn (N)

residues are assumed form interhelical hydrogen bonds in the core. L (green): hexaﬂ uoroleu-

cine. (b) Structures of β-alanine, NBD (donor ﬂ uorophore), and TAMRA (acceptor

ﬂ uorophore).

Plate 16.12 Front and back views of the CAT trimer. The three stabilizing mutations in L2-A1

are S87N, M142I in orange, and K46M in pink. Triﬂ uorolecuines/leucines are colored blue

and chloramphenicol red.

(Source: Montclare, J. K., Tirrell, D. A., Evolving proteins of novel composition. Angew. Chem.

Int. Ed. (2006) 45, 4518–4521. Copyright Wiley-VCH Verlag GmbH & Co. KGaA. Repro-

duced with permission.)

Plate 17.3 Cartoon stereo diagram of the x-ray structure of wild-type bacteriophage lambda

lysozyme as solved for the (GlcNAc)

complex and showing the position of the three methio-

nine residues in the enzyme (PDB 1d9u) [32].

Plate 17.4 Close-up of the detailed interactions between Met14 and adjacent residues and

the location of Met107 (PDB 1d9u) [32].

Plate 17.7 Crystal structure of the methionine–PtCl

complex (coordinates from Wilson

et al. [37]).

Plate 17.8 Ribbon diagram of the P. aeruginosa alkaline protease showing the active site

and the invariant methionine residue (PDB 1kap. [38]).

Plate 17.9 Close-up of the active-site region of P. aeruginosa alkaline protease showing Zn

and protein ligands and the position of the thiomethyl group in close proximity to these side-

chains (PDB 1kap. [38]).

Plate 17.10 (a) Stereo view of the active-site structure of P. aeruginosa azurin (PDB 4azu)

[46]. (b) Tube diagram of the P. aeruginosa azurin showing the section of protein that was

contributed by intein ligation.

Plate 17.11 X-ray structures of (a) DFM (PDB 1pfv) [48] and (b) TFM (PDB 1pfw) [48]

complexes with Met-tRNA synthetase from E. coli.

Plate 17.12 Stereo view of the active-site interactions of TFM with E. coli methionine ami-

nopeptidase (PDB 1c22) [49].