Total Synthesis of Camptothecin and SN-38

A new practical and concise total synthesis of enantiopure camptothecin and SN-38 (14% overall yield, 99.9% ee and 99.9% purity) was described, starting from inexpensive and readily available materials. The development of column chromatography-free purification was achieved in all steps, which offers an economic industrial process to the camptothecin-family alkaloids

Total Synthesis of Camptothecin and SN-38

A new practical and concise total synthesis of enantiopure camptothecin and SN-38 (14% overall yield, 99.9% ee and 99.9% purity) was described, starting from inexpensive and readily available materials. The development of column chromatography-free purification was achieved in all steps, which offers an economic industrial process to the camptothecin-family alkaloids

Structural analysis of inhibition of methionine aminopeptidase: implication of loop adaptability in selective inhibition of bacterial enzymes-0

<p><b>Copyright information:</b></p><p>Taken from "Structural analysis of inhibition of methionine aminopeptidase: implication of loop adaptability in selective inhibition of bacterial enzymes"</p><p>http://www.biomedcentral.com/1472-6807/7/84</p><p>BMC Structural Biology 2007;7():84-84.</p><p>Published online 19 Dec 2007</p><p>PMCID:PMC2238726.</p><p></p>own as green spheres, and the inhibitor is shown as sticks (yellow, carbon; red, oxygen; and blue, nitrogen). In ribbon drawing, the secondary structures are coded as red for α-helices, yellow for β-sheets, and green for loops and other structures. The YHGY loop (Y62, H63, G64 and Y65) is indicated by a red arrow

Structural analysis of inhibition of methionine aminopeptidase: implication of loop adaptability in selective inhibition of bacterial enzymes-2

<p><b>Copyright information:</b></p><p>Taken from "Structural analysis of inhibition of methionine aminopeptidase: implication of loop adaptability in selective inhibition of bacterial enzymes"</p><p>http://www.biomedcentral.com/1472-6807/7/84</p><p>BMC Structural Biology 2007;7():84-84.</p><p>Published online 19 Dec 2007</p><p>PMCID:PMC2238726.</p><p></p>d the nearby protein residues are shown as thin sticks. The two Mn(II) ions are shown as spheres and labelled as Mn1 and Mn2. The YHGY loop and residues Y62, H63, Y65 and W221, as well as Mn(II) ions, of each structure are coloured the same as the corresponding inhibitor: , yellow; , green; , cyan; , black; , magenta; , blue; , grey; and , red

Structural analysis of inhibition of methionine aminopeptidase: implication of loop adaptability in selective inhibition of bacterial enzymes-5

<p><b>Copyright information:</b></p><p>Taken from "Structural analysis of inhibition of methionine aminopeptidase: implication of loop adaptability in selective inhibition of bacterial enzymes"</p><p>http://www.biomedcentral.com/1472-6807/7/84</p><p>BMC Structural Biology 2007;7():84-84.</p><p>Published online 19 Dec 2007</p><p>PMCID:PMC2238726.</p><p></p>oloured cyan for the catalytic domain and blue for the N-terminal extension. (B) Overlay with human type II MetAP (PDB code ) that is coloured magenta for the catalytic domain, orange for the N-terminal extension and red for the insert. (C) Schematic drawing of the domains in MetAP and human MetAPs

Structural analysis of inhibition of methionine aminopeptidase: implication of loop adaptability in selective inhibition of bacterial enzymes-1

<p><b>Copyright information:</b></p><p>Taken from "Structural analysis of inhibition of methionine aminopeptidase: implication of loop adaptability in selective inhibition of bacterial enzymes"</p><p>http://www.biomedcentral.com/1472-6807/7/84</p><p>BMC Structural Biology 2007;7():84-84.</p><p>Published online 19 Dec 2007</p><p>PMCID:PMC2238726.</p><p></p>H79, H178) are shown. The bound inhibitors are (A), (B), (C), (D), and (E), respectively. The colour scheme is as follows: gray, carbon (protein residues); yellow, carbon (inhibitor); blue, nitrogen; red, oxygen; green, chlorine; and cyan, fluorine. Mn(II) ions are shown as green spheres. SigmaA-weighted -standard omit maps (inhibitor and metal ions were not included in the model for the structure-factor calculation) are shown superimposed on the refined structures as blue meshes contoured at 3.5 standard deviations of the resulting electron density map

Structural analysis of inhibition of methionine aminopeptidase: implication of loop adaptability in selective inhibition of bacterial enzymes-4

<p><b>Copyright information:</b></p><p>Taken from "Structural analysis of inhibition of methionine aminopeptidase: implication of loop adaptability in selective inhibition of bacterial enzymes"</p><p>http://www.biomedcentral.com/1472-6807/7/84</p><p>BMC Structural Biology 2007;7():84-84.</p><p>Published online 19 Dec 2007</p><p>PMCID:PMC2238726.</p><p></p>d inhibitors in the eight structures are: , ; , , , ; , ; , ; , ; , ; and , . All changes in distances smaller than the threshold 1σ are shown in grey; differences between this lower limit and an upper limit of 8σ are shown using a colour gradient where red stands for expansion and blue for contraction, light colours represent small changes and dark colours large changes; all differences larger than the upper limit are shown as full blue and full red, respectively. The gradients used for colour coding are also shown separately at the bottom of the figure. . Enlarged one of the matrices in A, showing the comparison between and . For clarity, the matrices underwent 2 × 2 binning (maintaining the element with the highest absolute value in the respective binning area) before being displayed