Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S010827010100840X/vj1138sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S010827010100840X/vj1138IIsup2.hkl |
CCDC reference: 174847
The synthesis of Cbz-ΔVal-OH, (I), was carried out by condensation of 2-oxo-3-methylbutanoic acid (1 g, 7.2 mmol) with benzyl carbamate (1.98 g, 10.8 mmol) and p-toluenesulfonic acid (0.47 g, 2.1 mmol) in dry benzene. The reaction mixture was refluxed at 373 K using a Dean–Stark water remover for 8 h. The solution was the extracted with saturated sodium bicarbonate. The extracts were neutralized by adding concentrated HCl dropwise to yield a white solid, which was filtered and recrystallized from benzene. The solid product of Cbz-ΔVal-OH was obtained at a yield of 67%. For the synthesis of Cbz-ΔVal-L-Trp-OCH3, (II), N-methylmorpholine (0.29 ml, 2.69 mmol) was added to a chilled (263 K) solution of (1) (0.67 g, 2.69 mmol) in tetrahydrofuran. This was followed by the addition of isobutyl chloroformate (0.36 ml, 2.69 mmol) and the resulting solution was stirred for 20 min. A precooled solution of L-Trp-OCH3·HCl (0.82 g, 3.2 mmol) was added (Trp is L-tryptophan) to the reaction mixture. This was stirred for 2 h at 273 K and then overnight at room temperature. After completion of the reaction (monitored by thin-layer chromatography), the solvent was removed under vacuum; the resulting residual material was dissolved in ethyl acetate and was washed successively with water, 10% sodium bicarbonate, 5% citric acid and water. The organic layer was dried over anhydrous sodium sulfate and then evaporated to yield 72% of compound (2) (m.p. 438 K). The peptide was crystallized from a solution in acetone–water (4:1) by slow evaporation.
All H atoms were visible in difference maps and were allowed for as riding atoms (with C—H distances of 0.93–0.98 Å and an N—H distance of 0.86 Å). In this light-atom structure, it was not possible to establish the absolute configuration from the Flack parameter [0.1 (3)]; the configuration chosen and shown in both the Scheme and Fig. 1 was determined by the configuration of the starting material in the synthesis (L-tryptophan).
Data collection: SDP (Enraf-Nonius, 1979); cell refinement: SDP; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 2001); software used to prepare material for publication: SHELXL97.
Fig. 1. The molecular structure of the designed peptide with the atom-numbering scheme and 30% probability displacement ellipsoids. |
C25H27N3O5 | F(000) = 952 |
Mr = 449.50 | Dx = 1.315 Mg m−3 |
Monoclinic, A2 | Cu Kα radiation, λ = 1.54180 Å |
a = 17.1524 (9) Å | Cell parameters from 25 reflections |
b = 6.1439 (9) Å | θ = 0–25° |
c = 22.6183 (11) Å | µ = 0.76 mm−1 |
β = 107.791 (12)° | T = 293 K |
V = 2269.6 (4) Å3 | Prism, colourless |
Z = 4 | 0.3 × 0.2 × 0.1 mm |
Enraf Nonius CAD-4 diffractometer | 2434 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.000 |
Graphite monochromator | θmax = 75.6°, θmin = 2.7° |
ω–2θ scans | h = 0→21 |
Absorption correction: empirical (using intensity measurements) (SDP; Enraf-Nonius, 1979) | k = 0→7 |
Tmin = 0.835, Tmax = 0.928 | l = −28→26 |
2576 measured reflections | 3 standard reflections every 60 min |
2576 independent reflections | intensity decay: none |
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.046 | H-atom parameters constrained |
wR(F2) = 0.146 | w = 1/[σ2(Fo2) + (0.1137P)2 + 0.5403P] where P = (Fo2 + 2Fc2)/3 |
S = 1.04 | (Δ/σ)max < 0.001 |
2576 reflections | Δρmax = 0.24 e Å−3 |
302 parameters | Δρmin = −0.25 e Å−3 |
1 restraint | Extinction correction: SHELXL97, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.0018 (4) |
C25H27N3O5 | V = 2269.6 (4) Å3 |
Mr = 449.50 | Z = 4 |
Monoclinic, A2 | Cu Kα radiation |
a = 17.1524 (9) Å | µ = 0.76 mm−1 |
b = 6.1439 (9) Å | T = 293 K |
c = 22.6183 (11) Å | 0.3 × 0.2 × 0.1 mm |
β = 107.791 (12)° |
Enraf Nonius CAD-4 diffractometer | 2434 reflections with I > 2σ(I) |
Absorption correction: empirical (using intensity measurements) (SDP; Enraf-Nonius, 1979) | Rint = 0.000 |
Tmin = 0.835, Tmax = 0.928 | 3 standard reflections every 60 min |
2576 measured reflections | intensity decay: none |
2576 independent reflections |
R[F2 > 2σ(F2)] = 0.046 | 1 restraint |
wR(F2) = 0.146 | H-atom parameters constrained |
S = 1.04 | Δρmax = 0.24 e Å−3 |
2576 reflections | Δρmin = −0.25 e Å−3 |
302 parameters |
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes. |
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. |
x | y | z | Uiso*/Ueq | ||
C1 | 0.25344 (16) | −0.1196 (5) | 0.42144 (11) | 0.0412 (6) | |
C2 | 0.32078 (19) | −0.0895 (7) | 0.47407 (13) | 0.0520 (7) | |
H2 | 0.3237 | 0.0346 | 0.4982 | 0.062* | |
C3 | 0.38262 (19) | −0.2397 (8) | 0.49081 (15) | 0.0614 (9) | |
H3 | 0.4270 | −0.2171 | 0.5261 | 0.074* | |
C4 | 0.37927 (19) | −0.4229 (8) | 0.45567 (16) | 0.0605 (9) | |
H4 | 0.4210 | −0.5256 | 0.4673 | 0.073* | |
C5 | 0.31380 (19) | −0.4548 (7) | 0.40293 (15) | 0.0550 (8) | |
H5 | 0.3119 | −0.5780 | 0.3786 | 0.066* | |
C6 | 0.25112 (17) | −0.3042 (6) | 0.38619 (13) | 0.0467 (7) | |
H6 | 0.2069 | −0.3274 | 0.3508 | 0.056* | |
C | 0.18659 (18) | 0.0482 (6) | 0.40716 (11) | 0.0488 (7) | |
HA | 0.1613 | 0.0466 | 0.4401 | 0.059* | |
HB | 0.2109 | 0.1907 | 0.4072 | 0.059* | |
O | 0.12362 (11) | 0.0172 (4) | 0.34845 (8) | 0.0448 (5) | |
CP | 0.14020 (15) | 0.1042 (5) | 0.29894 (11) | 0.0378 (5) | |
OP | 0.20673 (11) | 0.1712 (5) | 0.29888 (9) | 0.0502 (5) | |
N1 | 0.07163 (12) | 0.1100 (4) | 0.24917 (10) | 0.0368 (5) | |
H1 | 0.0282 | 0.0436 | 0.2509 | 0.044* | |
C1A | 0.07046 (13) | 0.2234 (4) | 0.19467 (11) | 0.0326 (5) | |
C1B | 0.02481 (16) | 0.1545 (5) | 0.13862 (12) | 0.0401 (6) | |
C1G1 | −0.0201 (2) | −0.0575 (6) | 0.13009 (15) | 0.0550 (8) | |
H1G1 | 0.0027 | −0.1478 | 0.1658 | 0.082* | |
H1G2 | −0.0150 | −0.1295 | 0.0938 | 0.082* | |
H1G3 | −0.0769 | −0.0312 | 0.1252 | 0.082* | |
C1G2 | 0.0107 (2) | 0.2848 (8) | 0.08027 (13) | 0.0588 (9) | |
H1G4 | 0.0237 | 0.4347 | 0.0907 | 0.088* | |
H1G5 | −0.0457 | 0.2728 | 0.0556 | 0.088* | |
H1G6 | 0.0450 | 0.2303 | 0.0571 | 0.088* | |
C1P | 0.10973 (13) | 0.4429 (4) | 0.20610 (10) | 0.0331 (5) | |
O1P | 0.09455 (11) | 0.5705 (4) | 0.24300 (9) | 0.0420 (4) | |
N2 | 0.15980 (13) | 0.4943 (4) | 0.17228 (10) | 0.0377 (5) | |
H2A | 0.1713 | 0.3961 | 0.1492 | 0.045* | |
C2A | 0.19466 (15) | 0.7091 (5) | 0.17368 (12) | 0.0386 (6) | |
H2A1 | 0.1589 | 0.8129 | 0.1857 | 0.046* | |
C2B | 0.28064 (15) | 0.7260 (5) | 0.22117 (13) | 0.0436 (6) | |
H2B1 | 0.3020 | 0.8708 | 0.2187 | 0.052* | |
H2B2 | 0.2758 | 0.7084 | 0.2625 | 0.052* | |
C2G | 0.34043 (15) | 0.5637 (5) | 0.21234 (12) | 0.0396 (6) | |
C2D1 | 0.35385 (17) | 0.3602 (6) | 0.23859 (14) | 0.0476 (7) | |
H2D1 | 0.3251 | 0.3009 | 0.2636 | 0.057* | |
N2E1 | 0.41537 (15) | 0.2569 (5) | 0.22285 (13) | 0.0530 (6) | |
H2E1 | 0.4328 | 0.1275 | 0.2340 | 0.064* | |
C2E2 | 0.44480 (16) | 0.3926 (6) | 0.18640 (13) | 0.0449 (6) | |
C2D2 | 0.39879 (15) | 0.5870 (5) | 0.17815 (12) | 0.0390 (5) | |
C2Z2 | 0.50991 (18) | 0.3654 (7) | 0.16256 (15) | 0.0543 (8) | |
H2Z2 | 0.5406 | 0.2378 | 0.1692 | 0.065* | |
C2H2 | 0.5271 (2) | 0.5339 (8) | 0.12881 (16) | 0.0627 (10) | |
H2H2 | 0.5702 | 0.5196 | 0.1122 | 0.075* | |
C2Z3 | 0.4814 (2) | 0.7276 (8) | 0.11871 (16) | 0.0609 (9) | |
H2Z3 | 0.4945 | 0.8390 | 0.0956 | 0.073* | |
C2E3 | 0.41698 (18) | 0.7539 (6) | 0.14292 (14) | 0.0488 (7) | |
H2E3 | 0.3863 | 0.8814 | 0.1357 | 0.059* | |
C2P | 0.19505 (18) | 0.7658 (6) | 0.10838 (15) | 0.0460 (7) | |
O2P | 0.18347 (19) | 0.6408 (6) | 0.06631 (11) | 0.0758 (8) | |
O3T | 0.21165 (17) | 0.9766 (5) | 0.10509 (13) | 0.0645 (7) | |
C3T | 0.2174 (3) | 1.0508 (10) | 0.0458 (2) | 0.0917 (16) | |
H3T1 | 0.2645 | 0.9864 | 0.0383 | 0.137* | |
H3T2 | 0.2226 | 1.2064 | 0.0463 | 0.137* | |
H3T3 | 0.1690 | 1.0088 | 0.0134 | 0.137* |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.0401 (12) | 0.0487 (15) | 0.0352 (11) | −0.0046 (13) | 0.0122 (10) | 0.0028 (12) |
C2 | 0.0498 (15) | 0.0600 (19) | 0.0421 (13) | −0.0093 (16) | 0.0081 (11) | −0.0052 (14) |
C3 | 0.0416 (15) | 0.086 (3) | 0.0485 (15) | −0.0040 (18) | 0.0021 (11) | 0.0019 (18) |
C4 | 0.0424 (14) | 0.078 (2) | 0.0601 (16) | 0.0105 (17) | 0.0146 (13) | 0.0085 (19) |
C5 | 0.0533 (16) | 0.0576 (19) | 0.0559 (15) | −0.0002 (16) | 0.0193 (12) | −0.0053 (16) |
C6 | 0.0419 (13) | 0.0532 (17) | 0.0419 (12) | −0.0074 (14) | 0.0080 (10) | −0.0017 (13) |
C | 0.0528 (15) | 0.0554 (18) | 0.0365 (11) | 0.0038 (15) | 0.0110 (10) | 0.0044 (13) |
O | 0.0418 (9) | 0.0535 (12) | 0.0392 (8) | 0.0018 (9) | 0.0124 (7) | 0.0120 (9) |
CP | 0.0349 (11) | 0.0405 (14) | 0.0392 (11) | 0.0038 (11) | 0.0131 (9) | 0.0061 (10) |
OP | 0.0330 (9) | 0.0658 (14) | 0.0498 (10) | −0.0062 (10) | 0.0096 (7) | 0.0124 (11) |
N1 | 0.0296 (9) | 0.0423 (12) | 0.0390 (10) | −0.0033 (9) | 0.0113 (8) | 0.0032 (9) |
C1A | 0.0261 (9) | 0.0348 (13) | 0.0379 (11) | 0.0018 (9) | 0.0114 (8) | 0.0008 (10) |
C1B | 0.0348 (11) | 0.0445 (15) | 0.0405 (12) | −0.0017 (11) | 0.0109 (9) | −0.0017 (12) |
C1G1 | 0.0498 (16) | 0.0515 (18) | 0.0573 (15) | −0.0133 (15) | 0.0069 (13) | −0.0080 (15) |
C1G2 | 0.0563 (17) | 0.078 (2) | 0.0357 (12) | −0.0079 (18) | 0.0050 (11) | 0.0038 (15) |
C1P | 0.0273 (10) | 0.0367 (13) | 0.0346 (10) | 0.0031 (10) | 0.0084 (8) | 0.0027 (10) |
O1P | 0.0410 (9) | 0.0409 (10) | 0.0486 (9) | −0.0014 (9) | 0.0205 (7) | −0.0040 (9) |
N2 | 0.0350 (10) | 0.0375 (12) | 0.0457 (10) | −0.0034 (9) | 0.0198 (8) | −0.0001 (9) |
C2A | 0.0341 (11) | 0.0354 (13) | 0.0509 (13) | −0.0023 (10) | 0.0199 (10) | 0.0028 (11) |
C2B | 0.0372 (12) | 0.0448 (16) | 0.0512 (14) | −0.0054 (12) | 0.0172 (10) | −0.0069 (12) |
C2G | 0.0336 (11) | 0.0383 (13) | 0.0450 (12) | −0.0036 (11) | 0.0091 (9) | −0.0002 (11) |
C2D1 | 0.0395 (13) | 0.0467 (15) | 0.0552 (15) | −0.0026 (13) | 0.0126 (11) | 0.0095 (14) |
N2E1 | 0.0446 (12) | 0.0420 (13) | 0.0677 (15) | 0.0045 (12) | 0.0105 (11) | 0.0077 (13) |
C2E2 | 0.0354 (12) | 0.0451 (16) | 0.0499 (13) | −0.0040 (12) | 0.0065 (10) | −0.0057 (13) |
C2D2 | 0.0324 (11) | 0.0402 (13) | 0.0421 (12) | −0.0038 (11) | 0.0081 (9) | −0.0032 (11) |
C2Z2 | 0.0390 (13) | 0.061 (2) | 0.0604 (17) | 0.0062 (15) | 0.0118 (12) | −0.0130 (17) |
C2H2 | 0.0469 (15) | 0.085 (3) | 0.0636 (17) | −0.0051 (19) | 0.0275 (14) | −0.019 (2) |
C2Z3 | 0.0548 (17) | 0.078 (3) | 0.0573 (17) | −0.0141 (19) | 0.0281 (14) | 0.0033 (19) |
C2E3 | 0.0439 (14) | 0.0493 (17) | 0.0546 (15) | −0.0054 (14) | 0.0169 (11) | 0.0040 (14) |
C2P | 0.0399 (13) | 0.0473 (15) | 0.0540 (15) | 0.0007 (13) | 0.0188 (11) | 0.0119 (14) |
O2P | 0.097 (2) | 0.080 (2) | 0.0558 (13) | −0.0109 (18) | 0.0316 (13) | 0.0013 (15) |
O3T | 0.0718 (15) | 0.0503 (14) | 0.0840 (16) | 0.0009 (13) | 0.0425 (13) | 0.0228 (13) |
C3T | 0.102 (3) | 0.088 (4) | 0.106 (3) | 0.023 (3) | 0.063 (3) | 0.053 (3) |
C1—C6 | 1.380 (5) | C1P—N2 | 1.351 (3) |
C1—C2 | 1.395 (4) | N2—C2A | 1.445 (4) |
C1—C | 1.502 (4) | N2—H2A | 0.86 |
C2—C3 | 1.369 (5) | C2A—C2P | 1.520 (4) |
C2—H2 | 0.93 | C2A—C2B | 1.540 (4) |
C3—C4 | 1.369 (6) | C2A—H2A1 | 0.98 |
C3—H3 | 0.93 | C2B—C2G | 1.487 (4) |
C4—C5 | 1.380 (5) | C2B—H2B1 | 0.97 |
C4—H4 | 0.93 | C2B—H2B2 | 0.97 |
C5—C6 | 1.381 (5) | C2G—C2D1 | 1.373 (5) |
C5—H5 | 0.93 | C2G—C2D2 | 1.447 (4) |
C6—H6 | 0.93 | C2D1—N2E1 | 1.368 (4) |
C—O | 1.446 (3) | C2D1—H2D1 | 0.93 |
C—HA | 0.97 | N2E1—C2E2 | 1.373 (4) |
C—HB | 0.97 | N2E1—H2E1 | 0.86 |
O—CP | 1.347 (3) | C2E2—C2Z2 | 1.391 (4) |
CP—OP | 1.214 (3) | C2E2—C2D2 | 1.412 (4) |
CP—N1 | 1.357 (3) | C2D2—C2E3 | 1.391 (4) |
N1—C1A | 1.411 (3) | C2Z2—C2H2 | 1.371 (6) |
N1—H1 | 0.86 | C2Z2—H2Z2 | 0.93 |
C1A—C1B | 1.339 (3) | C2H2—C2Z3 | 1.405 (6) |
C1A—C1P | 1.494 (3) | C2H2—H2H2 | 0.93 |
C1B—C1G1 | 1.495 (4) | C2Z3—C2E3 | 1.384 (4) |
C1B—C1G2 | 1.499 (4) | C2Z3—H2Z3 | 0.93 |
C1G1—H1G1 | 0.96 | C2E3—H2E3 | 0.93 |
C1G1—H1G2 | 0.96 | C2P—O2P | 1.191 (5) |
C1G1—H1G3 | 0.96 | C2P—O3T | 1.333 (4) |
C1G2—H1G4 | 0.96 | O3T—C3T | 1.449 (4) |
C1G2—H1G5 | 0.96 | C3T—H3T1 | 0.96 |
C1G2—H1G6 | 0.96 | C3T—H3T2 | 0.96 |
C1P—O1P | 1.229 (3) | C3T—H3T3 | 0.96 |
C6—C1—C2 | 118.2 (3) | C1P—N2—C2A | 122.1 (2) |
C6—C1—C | 123.7 (2) | C1P—N2—H2A | 118.9 |
C2—C1—C | 118.1 (3) | C2A—N2—H2A | 118.9 |
C3—C2—C1 | 121.1 (3) | N2—C2A—C2P | 108.2 (2) |
C3—C2—H2 | 119.5 | N2—C2A—C2B | 112.3 (2) |
C1—C2—H2 | 119.5 | C2P—C2A—C2B | 112.0 (2) |
C2—C3—C4 | 120.1 (3) | N2—C2A—H2A1 | 108.1 |
C2—C3—H3 | 119.9 | C2P—C2A—H2A1 | 108.1 |
C4—C3—H3 | 119.9 | C2B—C2A—H2A1 | 108.1 |
C3—C4—C5 | 119.8 (4) | C2G—C2B—C2A | 114.4 (2) |
C3—C4—H4 | 120.1 | C2G—C2B—H2B1 | 108.6 |
C5—C4—H4 | 120.1 | C2A—C2B—H2B1 | 108.6 |
C4—C5—C6 | 120.1 (4) | C2G—C2B—H2B2 | 108.6 |
C4—C5—H5 | 119.9 | C2A—C2B—H2B2 | 108.6 |
C6—C5—H5 | 119.9 | H2B1—C2B—H2B2 | 107.6 |
C1—C6—C5 | 120.7 (3) | C2D1—C2G—C2D2 | 105.6 (3) |
C1—C6—H6 | 119.7 | C2D1—C2G—C2B | 125.7 (3) |
C5—C6—H6 | 119.7 | C2D2—C2G—C2B | 128.6 (3) |
O—C—C1 | 114.5 (3) | N2E1—C2D1—C2G | 110.5 (3) |
O—C—HA | 108.6 | N2E1—C2D1—H2D1 | 124.7 |
C1—C—HA | 108.6 | C2G—C2D1—H2D1 | 124.7 |
O—C—HB | 108.6 | C2D1—N2E1—C2E2 | 109.2 (3) |
C1—C—HB | 108.6 | C2D1—N2E1—H2E1 | 125.4 |
HA—C—HB | 107.6 | C2E2—N2E1—H2E1 | 125.4 |
CP—O—C | 115.0 (2) | N2E1—C2E2—C2Z2 | 130.2 (3) |
OP—CP—O | 125.0 (2) | N2E1—C2E2—C2D2 | 107.4 (3) |
OP—CP—N1 | 124.5 (2) | C2Z2—C2E2—C2D2 | 122.2 (3) |
O—CP—N1 | 110.5 (2) | C2E3—C2D2—C2E2 | 119.0 (3) |
CP—N1—C1A | 121.0 (2) | C2E3—C2D2—C2G | 133.8 (3) |
CP—N1—H1 | 119.5 | C2E2—C2D2—C2G | 107.2 (3) |
C1A—N1—H1 | 119.5 | C2H2—C2Z2—C2E2 | 117.4 (3) |
C1B—C1A—N1 | 121.3 (2) | C2H2—C2Z2—H2Z2 | 121.3 |
C1B—C1A—C1P | 123.5 (2) | C2E2—C2Z2—H2Z2 | 121.3 |
N1—C1A—C1P | 114.2 (2) | C2Z2—C2H2—C2Z3 | 121.7 (3) |
C1A—C1B—C1G1 | 121.8 (3) | C2Z2—C2H2—H2H2 | 119.1 |
C1A—C1B—C1G2 | 123.7 (3) | C2Z3—C2H2—H2H2 | 119.1 |
C1G1—C1B—C1G2 | 114.4 (3) | C2E3—C2Z3—C2H2 | 120.5 (4) |
C1B—C1G1—H1G1 | 109.5 | C2E3—C2Z3—H2Z3 | 119.7 |
C1B—C1G1—H1G2 | 109.5 | C2H2—C2Z3—H2Z3 | 119.7 |
H1G1—C1G1—H1G2 | 109.5 | C2Z3—C2E3—C2D2 | 119.1 (3) |
C1B—C1G1—H1G3 | 109.5 | C2Z3—C2E3—H2E3 | 120.4 |
H1G1—C1G1—H1G3 | 109.5 | C2D2—C2E3—H2E3 | 120.4 |
H1G2—C1G1—H1G3 | 109.5 | O2P—C2P—O3T | 124.6 (3) |
C1B—C1G2—H1G4 | 109.5 | O2P—C2P—C2A | 125.4 (3) |
C1B—C1G2—H1G5 | 109.5 | O3T—C2P—C2A | 110.0 (3) |
H1G4—C1G2—H1G5 | 109.5 | C2P—O3T—C3T | 115.7 (4) |
C1B—C1G2—H1G6 | 109.5 | O3T—C3T—H3T1 | 109.5 |
H1G4—C1G2—H1G6 | 109.5 | O3T—C3T—H3T2 | 109.5 |
H1G5—C1G2—H1G6 | 109.5 | H3T1—C3T—H3T2 | 109.5 |
O1P—C1P—N2 | 122.6 (3) | O3T—C3T—H3T3 | 109.5 |
O1P—C1P—C1A | 121.0 (2) | H3T1—C3T—H3T3 | 109.5 |
N2—C1P—C1A | 116.4 (2) | H3T2—C3T—H3T3 | 109.5 |
C6—C1—C2—C3 | −0.6 (5) | C2P—C2A—C2B—C2G | −66.3 (3) |
C—C1—C2—C3 | 178.0 (3) | C2A—C2B—C2G—C2D1 | −89.7 (3) |
C1—C2—C3—C4 | 0.2 (5) | C2A—C2B—C2G—C2D2 | 93.8 (3) |
C2—C3—C4—C5 | 0.7 (6) | C2D2—C2G—C2D1—N2E1 | −0.4 (3) |
C3—C4—C5—C6 | −1.1 (5) | C2B—C2G—C2D1—N2E1 | −177.5 (3) |
C2—C1—C6—C5 | 0.2 (4) | C2G—C2D1—N2E1—C2E2 | 0.9 (3) |
C—C1—C6—C5 | −178.3 (3) | C2D1—N2E1—C2E2—C2Z2 | 175.6 (3) |
C4—C5—C6—C1 | 0.6 (5) | C2D1—N2E1—C2E2—C2D2 | −1.1 (3) |
C6—C1—C—O | −7.9 (4) | N2E1—C2E2—C2D2—C2E3 | 179.6 (2) |
C2—C1—C—O | 173.6 (2) | C2Z2—C2E2—C2D2—C2E3 | 2.6 (4) |
C1—C—O—CP | −85.5 (3) | N2E1—C2E2—C2D2—C2G | 0.8 (3) |
C—O—CP—OP | 12.5 (4) | C2Z2—C2E2—C2D2—C2G | −176.1 (3) |
C—O—CP—N1 | −166.4 (2) | C2D1—C2G—C2D2—C2E3 | −178.8 (3) |
OP—CP—N1—C1A | −8.6 (4) | C2B—C2G—C2D2—C2E3 | −1.8 (5) |
O—CP—N1—C1A | 170.4 (2) | C2D1—C2G—C2D2—C2E2 | −0.3 (3) |
CP—N1—C1A—C1B | 147.4 (3) | C2B—C2G—C2D2—C2E2 | 176.7 (3) |
CP—N1—C1A—C1P | −44.2 (3) | N2E1—C2E2—C2Z2—C2H2 | −177.9 (3) |
N1—C1A—C1B—C1G1 | −6.6 (4) | C2D2—C2E2—C2Z2—C2H2 | −1.7 (4) |
C1P—C1A—C1B—C1G1 | −173.9 (2) | C2E2—C2Z2—C2H2—C2Z3 | 0.3 (5) |
N1—C1A—C1B—C1G2 | 170.1 (3) | C2Z2—C2H2—C2Z3—C2E3 | 0.1 (5) |
C1P—C1A—C1B—C1G2 | 2.8 (4) | C2H2—C2Z3—C2E3—C2D2 | 0.9 (5) |
C1B—C1A—C1P—O1P | 121.8 (3) | C2E2—C2D2—C2E3—C2Z3 | −2.1 (4) |
N1—C1A—C1P—O1P | −46.4 (3) | C2G—C2D2—C2E3—C2Z3 | 176.2 (3) |
C1B—C1A—C1P—N2 | −56.0 (3) | N2—C2A—C2P—O2P | −13.0 (4) |
N1—C1A—C1P—N2 | 135.9 (2) | C2B—C2A—C2P—O2P | 111.3 (4) |
O1P—C1P—N2—C2A | −4.5 (4) | N2—C2A—C2P—O3T | 168.0 (2) |
C1A—C1P—N2—C2A | 173.1 (2) | C2B—C2A—C2P—O3T | −67.8 (3) |
C1P—N2—C2A—C2P | −141.6 (2) | O2P—C2P—O3T—C3T | −1.6 (5) |
C1P—N2—C2A—C2B | 94.3 (3) | C2A—C2P—O3T—C3T | 177.4 (3) |
N2—C2A—C2B—C2G | 55.7 (3) |
Experimental details
Crystal data | |
Chemical formula | C25H27N3O5 |
Mr | 449.50 |
Crystal system, space group | Monoclinic, A2 |
Temperature (K) | 293 |
a, b, c (Å) | 17.1524 (9), 6.1439 (9), 22.6183 (11) |
β (°) | 107.791 (12) |
V (Å3) | 2269.6 (4) |
Z | 4 |
Radiation type | Cu Kα |
µ (mm−1) | 0.76 |
Crystal size (mm) | 0.3 × 0.2 × 0.1 |
Data collection | |
Diffractometer | Enraf Nonius CAD-4 diffractometer |
Absorption correction | Empirical (using intensity measurements) (SDP; Enraf-Nonius, 1979) |
Tmin, Tmax | 0.835, 0.928 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 2576, 2576, 2434 |
Rint | 0.000 |
(sin θ/λ)max (Å−1) | 0.628 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.046, 0.146, 1.04 |
No. of reflections | 2576 |
No. of parameters | 302 |
No. of restraints | 1 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.24, −0.25 |
Computer programs: SDP (Enraf-Nonius, 1979), SDP, SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), PLATON (Spek, 2001), SHELXL97.
α,β-Dehydroamino acids are strong inducers of folded conformations in peptides. A set of design rules have been developed with dehydrophenylalanine (ΔPhe), dehydroleucine (ΔLeu), dehydro-α-aminobutyric acid (ΔAbu) and dehydroalanine (ΔAla) (Singh & Kaur, 1996). However, the branched β-carbon residues such as valine and isoleucine have not been used so far as dehydro residues though the conformational preferences of valine and isoleucine are known to be different than other residues. In order to develop new design rules with dehydrovaline (ΔVal) and dehydroisoleucine (ΔIle), the structure of a dipeptide, (II), with ΔVal has been determined.
The structure (Fig. 1) shows that the C1A—C1B distance of 1.339 (3) Å in ΔVal corresponds to a standard C═C double-bond distance of 1.32 Å (Rose et al., 1985). Due to unfavourable interactions between the atoms of the backbone and those of the side chain, the closing of the angle N1—C1A—C1P to 114.2 (2)° occurs. The other two angles N1—C1A—C1B and C1P—C1A—C1B are 121.3 (2) and 123.5 (2)°, respectively.
The peptide adopts a conformation characterized by torsion angles, ϕ1 (CP–N1–C1A–C1P) = -44.2 (3)°, ψ1 (N1–C1A–C1P–N2) = 135.9 (2)°, ϕ2 (C1P–N2–C2A–C2P) = -141.6 (2)° and ψ2T (N2–C2A–C2P–O3T) = 168.0 (2)°. It may be noted that the values of torsion angles of ΔVal correspond to the ϕ,ψ values of an (i+1)t h residue in a β-turn II conformation. It indicates that the ΔVal residue at (i+1) position may promote a β-turn II conformation. The values of torsion angles χ11,1 (N1–C1A–C1B–C1G1) and χ11,2 (N1–C1A–C1B–C1G2) of dehydrovaline are -6.6 (4) and 170.1 (3)°, respectively, and indicate that the side chain of ΔVal is essentially planar.
The crystal packing is stabilized by a hydrophobic region formed by the aromatic rings of tryptophans and benzene rings of carbobenzoxy (Cbz) groups. The packing is further stabilized by an intermolecular hydrogen bond formed between the screw axis related NH and CO groups of ΔVal residue [N1—H1···O1Pi, with N1···OPi = 2.919 (3) Å, H1···O1Pi = 2.16 Å and N1–H1···O1Pi = 147°; symmetry code: (i) -x, y - 1/2, -z + 1/2].