Asymmetirc ascidiacyclamide analogues

One amino acid was replaced to disturb C2-symmetry


Reference: Akiko Asano, Katsuhiko Minoura, Takeshi Yamada, Atsushi Numata, Toshimasa Ishida, Yoshio Katsuya, Yoshihiro Mezaki, Masahiro Sasaki, Taizo Taniguchi, Masamichi Nakai, Hiroshi Hasegawa, Akira Terashima, and Mitsunobu Doi (2002) J. Pept. Res. 60, 10-22. Effect of asymmetric modification on the conformation of ascidiacyclamide analogues.

[Ala1]ASC (folded)
[Aib1]ASC (folded)

[Phe1]ASC (folded)
[Val1]ASC (square)
These figures were produced from Rasmol and rendered by POVray3
Table 1. Crystal and experimental data for ASC analogues 
                  [Ala1]ASC          [Phe1]ASC         [Val1]ASC         [Aib1]ASC

  Formula        C33H46N8O6S2    C39H50N8O6S2.H2O   2(C35H50N8O6S2)    C34H48N8O6S2
  Mr                714.9             809.1             1485.9           728.92
  Crystal system  monoclinic       orthorhombic        triclinic        monoclinic
  Space group        P21             P212121              P1               P21
     a, A         12.871(7)          8.4525(1)         10.6287(2)       12.9839(4)
     b, A         10.159(5)         14.3982(2)         14.1562(6)       10.1151(3)
     c, A         14.377(7)         33.8976(5)         14.3489(5)       14.4747(5)
     a, deg          90                90              72.429(2)           90
     b, deg       103.01(4)            90              83.660(2)        104.123(2)
     g, deg          90                90              82.641(3)           90
     V, A3        1831.6(16)         4125.4(1)         2035.4(1)        1843.55(10)
     Z               2                  4                  2               2
     T, K           240                240                100             100
  Dx, g cm-3       1.301              1.303              1.212           1.313
  F(000)            832                1720               792             776
  X-ray source     Cu Ka           synchrotron        synchrotron      synchrotron
  lambda, A        1.5418             0.834              0.835            0.835
  m, mm-1          1.822              0.187              0.182            0.199
  No. of reflx     4682               4855               7441             3947
  No. of para       450                515               940              461
     R             0.0593            0.0390              0.0667           0.0435
     wR            0.1479            0.0973              0.1850           0.1236
  Flack x         -0.03(3)           0.54(8)             0.15(9)          0.04(10)
  (D/s)max       < 0.001           < 0.001               0.001          < 0.001
  Drmax, e A3      0.498             0.362               1.018            0.392
  Drmin, e A3     -0.275            -0.294              -0.480           -0.409
  - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 
   Get PDB          yes               yes                 yes               yes
  - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
The beam time of synchrotron, SPring-8/BL24XU-A, for this study was provided by Hyogo Prefecture and the Japan Synchrotron Radiation Research Institute (Approval No. C99A24XU-005N).
Analogues were further analyzed by NMR and CD spectroscopic methods. Summary is listed in Table 2.
Table 2. Summary of structural properties and cytotoxic activities of ASC analogues 
                Form(a)     Temp.   Solvent dep(d)  Conc.   CD spectra(f)       Cyto-
             X-ray  NMR(b)  dep(c)  DMSO  acetone   dep(e)  MeCN    TFE      toxicity(g)

 [Gly1]ASC           F                      ++      +++     [+, 0]  [++, ++]    (-)
 [Ala1]ASC    F               +      ++     ++       +      [+, 0]  [++, ++]    +-
 [Aib1]ASC    F              ++       +     ++       +      [+, 0]  [++, ++]     -
 [Val1]ASC    S               +      ++      +       +      [++, -] [++, ++]    +++
 [Ile]ASC     S(h)            +      ++     ++       +      [+, -]  [++, ++]     ++
 [Leu1]ASC    S(i)   S        +      ++     ++       +      [+, +]  [++, ++]    (++)
 [Phe1]ASC    F      F        +      ++     ++      ++      [+-, +] [++, ++]     ++
 [D-Ile1]ASC                 +++     ++     +++     ++      [++, 0] [++, ++]      +
 [Val3]ASC                   +++     +++    +++      +      [+, -]  [+, -]       ++
a 'F' and 'S' represent folded and square forms, respectively.
b Molecular dynamics simulations are reported.
c Number of signs shows degree of temperature dependences (Dd/DT).
d Number of signs shows intensity of solvent effects.
e Number of signs shows effect of peptide concentration on chemical shifts.
f [q] values of 250-210 nm and 280-250 nm are indicated by left and right signs
in brackets, respectively.
g Number of signs shows degree of cytotoxic activity in P388 cells.
Activities taken from the previous report using L1012 cells are shown in parentheses.
h Crystal structures from various solvent systems were analyzed, and
all structures showed the square form .
i The structure is taken from the previous report.
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