COMMUNICATIONS
3H; H5), 6.96 (d, 3J(H4,H3) 7.8 Hz, 3H; H3), 7.39 (dd, 3J(H3,H4)
7.8 Hz, 3J(H4,H5) 7.8Hz, 3H; H4). Elemental analysis (%) calcd for
C33H51N7: C 72.62, H 9.42, N 17.96; found: C 72.59, H 9.20, N 17.80.
0.079, and Rw 0.113. Crystallographic data (excluding structure
factors) for the structures reported in this paper have been deposited
with the Cambridge Crystallographic Data Centre as supplementary
publication no. CCDC-101084. Copies of the data can be obtained free
of charge on application to CCDC, 12 Union Road, Cambridge
CB21EZ, UK (fax: (44)1223-336-033; e-mail: deposit@ccdc.cam.
ac.uk).
1: A solution of PhCOONa (72 mg, 0.05 mmol) in H2O (2.5 mL) was added
to a solution of Fe(ClO4)3 ´ xH2O (177.1 mg, 0.5 mmol) and tnpa (273.0 mg,
0.5 mmol) in acetonitrile (10 mL). After stirring for 1 h, the solution was
concentrated to give a purple powder of 1, which was collected by filtration,
washed with a small amount of diethyl ether, and dried in vacuo (yield:
89%). Elemental analysis (%) calcd for C40H59N7O8Cl1Fe1: C 55.70, H 7.15,
N 11.37; found: C 56.04, H 6.94, N 11.44.
[9] a) M. Harata, K. Jitsukawa, H. Masuda, and H. Einaga, Chem. Lett.
1996, 813 ± 814; b) A. Wada, M. Harata, K. Hasegawa, M. Mukai, T.
Kitagawa, H. Masuda, H. Einaga, Angew. Chem. 1998, 110, 874 ± 875;
Angew. Chem. Int. Ed. 1998, 37, 798 ± 799.
2: Fe(ClO4)3 ´ xH2O (177.1 mg, 0.5 mmol) was dissolved in methanol
containing molecular sieves (3 ). After 24 h, tnpa (273.0 mg, 0.5 mmol)
was added to this solution. After stirring for 30 min, the mixture was
concentrated to give a yellow-orange powder of 2, which was collected by
filtration and dried in vacuo (yield: 65%). Elemental analysis (%)calcd for
C35H57N7O6Cl1Fe1: C 55.08, H 7.53, N 12.85; found: C, 54.90, H, 7.72, N,
12.72.
[10] S. Slappendel, B. G. Malmström, L. Petersson, A. Ehrenberg, G. A.
Veldink, J. F. G. Vliegenthart, Biochem. Biophy. Res. Commun. 1982,
108, 673 ± 677.
[11] An API 300 triple quadrupole mass spectrometer (PE-Sciex) in
positive-ion detection mode, equipped with an ion spray interface, was
used for these ESI-MS experiments. The sprayer was held at a
potential of 4.5 kV and compressed N2 was employed to assist liquid
nebulization. The orifice potential was maintained at 25 V.
[12] M. R. Egmond, P. M. Fasella, G. A. Veldink, J. F. G. Vliegenthart, J.
Boldingh, Eur. J. Biochem. 1977, 76, 469 ± 479.
Received: January 16, 1998 [Z11385IE]
German version: Angew. Chem. 1998, 110, 2198 ± 2200
[13] Another example of a (methoxo)iron(iii) complex with such a color
Keywords: bioinorganic chemistry ´ enzyme mimetics ´ iron
(red-orange)
is
[Fe{2,6-[(2-C5H4N)CH2OCH2]2C5H3N}(OMe)]-
(OSO2CF3)2 (2-C5H4N 2-Pyridyl, C5H3N 2,6-Pyridindiyl).[6b]
.
[14] M. Harata, K. Jitsukawa, H. Masuda, H. Einaga, Chem. Lett. 1995,
61 ± 62.
[1] Reviews: a) M. J. Nelson, S. P. Seitz in Active Oxygen in Biochemistry
(Eds.: J. S. Valentine, C. S. Foote, A. Greenberg, J. F. Liebman),
Chapman & Hall, London, 1995, pp. 276 ± 312; b) L. Que, Jr., R. Y. N.
Ho, Chem. Rev. 1996, 96, 2607 ± 2624.; c) T. Funabiki in Oxygenases
and Model Systems (Ed.: T. Funabiki), Kluwer Academic, Dordrecht,
1997, pp. 69 ± 77, 140 ± 145.
[2] EPR studies: a) S. Slappendel, G. A. Veldink, J. F. G. Vliegenthart, R.
Aasa, B. G. Malmström, Biochim. Biophys. Acta 1981, 667, 77 ± 86;
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7144 ± 7148; c) M. J. Nelson, J. Am. Chem. Soc. 1988, 110, 2985 ± 2986.
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Trimitsis, C. P. Buck, G. N. Grove, R. A. Cowling, M. J. Nelson,
Biochemistry 1994, 33, 15023 ± 15035; b) L. M. Van der Heijdt, M. C.
Feiters, S. Navaratnam, H.-F. Nolting, C. Hermes, G. A. Veldink,
J. F. G. Vliegenthart, Eur. J. Biochem. 1992, 207, 793 ± 802.
[4] Magnetic circular dichroism studies: a) M. A. Pavlosky, Y. Zhang,
T. E. Westre, Q.-F. Gan, E. G. Pavel, C. Campochiaro, B. Hedman,
K. O. Hodgson, E. I. Solomon, J. Am. Chem. Soc. 1995, 117, 4316 ±
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1991, 113, 5162 ± 5175.
A Photochemical Switch for Controlling
Protein ± Protein Interactions**
Sonia K. Pollitt and Peter G. Schultz*
Photocaged small molecules and proteins, molecules that
can rapidly be converted from inactive into active form with
light, have proven to be very useful tools in biology.[1] The
ability to control protein ± protein binding interactions would
further extend this approach to a large number of cellular
processes including signal transduction pathways, gene regu-
lation, and protein trafficking. Chemical modification has
been used to introduce photocleavable groups into proteins,
but this method depends on a uniquely reactive residue being
present on the protein surface in order to achieve high
selectivity.[2] Here we use unnatural amino acid mutagenesis
to photocage the interaction of the p21ras (ras) protein with its
downstream effector p120 ± GAP (GAP GTPase-activating
protein). The caged ras protein, in which Asp38 is substituted
with the b-o-nitrobenzyl ester of aspartic acid (Nb-Asp),
retains its intrinsic GTPase activity but is unable to interact
[5] Crystallographic studies of the catalytically inactive iron(ii) form of
SLO-1: a) J. C. Boyington, B. J. Gaffney, L. M. Amzel, Science 1993,
260, 1482 ± 1486; b) W. Minor, J. Steczko, J. T. Bolin, Z. Otwinowski, B.
Axelrod, Biochemistry 1993, 32, 6320 ± 6323.
[6] a) S. K. Mandal, L. Que, Jr., Inorg. Chem. 1997, 36, 5424 ± 5425;
b) R. T. Jonas, T. D. P. Stack, J. Am. Chem. Soc. 1997, 119, 8566 ± 8567;
c) Y. Zang, T. E. Elgren, Y. Dong, L. Que, Jr, J. Am. Chem. Soc. 1993,
115, 811 ± 813; d) Y. Zang, J. Kim, Y. Dong, E. C. Wilkinson, E. H.
Appelman, L. Que, Jr, J. Am. Chem. Soc. 1997, 119, 4197 ± 4205;
e) D. D. Cox, S. J. Benkovic, L. M. Bloom, F. C. Bradley, M. J. Nelson,
L. Que, Jr., D. E. Wallick, J. Am. Chem. Soc. 1988, 110, 2026 ± 2032;
f) S. Hikichi, T. Ogihara, K. Fujisawa, N. Kitajima, M. Akita, Y. Moro-
oka, Inorg. Chem. 1997, 36, 4539 ± 4547; g) J. W. Buchler, K. L. Lay,
Y. J. Lee, W. R. Scheidt, Angew. Chem. 1982, 94, 456; Angew. Chem.
Int. Ed. Engl. 1982, 21, 432; h) Y. Dong, H. Fujii, M. P. Hendrich, R. A.
Leising, G. Pan, C. R. Randall, E. C. Wilkinson, Y. Zang, L. Que, Jr.,
B. G. Fox, K. Kauffman, E. Münck, J. Am. Chem. Soc. 1995, 117,
2778 ± 2792; i) A. Hazell, K. B. Jensen, C. J. McKenzie, H. Toftlund,
Inorg. Chem. 1994, 33, 3127 ± 3134.
[*] P. G. Schultz, S. K. Pollitt
Howard Hughes Medical Institute and
Department of Chemistry
University of California, Berkeley and
Lawrence Berkeley National Laboratory
Berkeley, CA 94720 (USA)
[7] IR spectra of the compounds in acetonitrile at ambient temperature
Fax: (1)510-643-6890
were measured on a ReactIR 1000 spectrometer (ASI Applied
1
Systems) over the range 4000 ± 650 cm
.
[8] Purple crystals suitable for X-ray structure analysis were obtained
from an acetonitrile/diethyl ether solution. Crystal data for 1:
C40H59FeClO8N7, Mw 857.25, monoclinic, space group P21/c
(No. 14), a 10.720(1), b 16.390(2), c 26.23(1) , b 100.40(2)8,
V 4532(1) 3, Z 4, 1calcd 1.256 gcm 3, m(MoKa) 4.46 cm 1, R
[**] We thank N. Damrauer and J. McCusker for helpful advice and the
use of their laser, and H. Chung for the GAP protein. We are grateful
for financial support for this work from the National Institutes of
Health (grant no. R02 GM49220). P.G.S. is a Howard Hughes Medical
Institute Investigator.
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