7352 and to Dr. Robert Hershfield for his valuable assistance in the analysis of Scheme 11.
moiety of Kacetyltyrosine pchloroanilide in the side-chain and leavinggroup subsites are calculated from the following determinant.
References and Notes
N-Acyl amino
(1)This work was supported by a Public Health Service Research Career Development Award (l-K4-GM-l0010-02) from the National institute for General Medical Sciences and by a grant (DE-03246) from the National Institutes of Health. (2)(a) M. Caplow, J. Am. Chem. Soc., 91,3639 (1969);(b) E. C.Lucas and M. Caplow, /bid., 94,960 (1972);(c) A. R. Fersht and Y. Requena. /bid.. 93, 7079 (1971);(d) E. C. Lucas, M. Caplow. and K. J. Bush, ibid., 95,
2670 (1973). (3)M. H. O'Leary and M. D. Kiuetz, J. Am. Chem. SOC.,94, 3565 (1972). (4)A. R. Fersht and Y. Requena, J. Mol. Bioi., 60,279 (1971). (5) Abbreviatlons used are HCD-Phe-NH2, Kformyl-L-phenylalanine amide; HCO-D-Phe-NH2, Kformyl-o-phenylalanine amide; HCO-Phe-FH, Kformyi-L-phenylalanine formylhydrazide; HCO-D-Phe-FH, Kformyl-D-phenylalanine formylhydrazlde; HCO-MePhe-FH, Kformyl-Kmethyl-L-phenyialanine formylhydrazide; Ac-Tyr-NHPhCl, Kacetyl-L-tyroslne pchloroanilide; Ac-D-Tyr-NHPhCI, Kacetyl-D-tyrosine pchioroaniiide; AcMeTyr-NHPhCI, Kacetyl-Kmethyl-L-tyrosine pchloroanilide. (6) K. R. Hanson. R. Llna. and E. Havir. 8iochem. BioDhvs. . . Res. Commun.. 29, 194 (1967). (7)S.A. Bernhard, W. C. Coles, and J. F. Nowell, J. Am. Chem. SOC.,82,
3043 (1960). (8)(a) L. W. Cunningham and C. S.Brown, J. 8loi. Chem., 221, 287 (1956); (b) E. Zeeberg, M. Caswell, and M. Caplow, J. Am. Chem. Soc., 95,
2734 (1973). (9)Dr. G, L. Schmlr has calculated an equilibrlum constant equal to 3 X for formlng a neutral tetrahedral Intermediate In the nonenzymatic Intramolecular cycllzatlon of 4-hydroxybutyranlllde (prlvate cornmunhatlon). (10)(a) A. Ruhlman, D. Kukla, P. Schwager, K. Bartels, and R. Huber, J. Mol. Biol, 77, 417 (1973);(b) R. M. Sweet, H. T. Wrlght, J. Janln, C. H. Chothla, and D. M. Blow, Biochem/stry, 13, 4212 (1974). (11) (a) C. L. Hamilton, C. Nlemann, and 0. S. Hammond, Prococ. Net/. Aced. Sci. U.S.A., 55, 684 (1966).(b) Nlemann's determlnant formulation 1s based on the Idea that for multlple mutually exclusive bindlng modes, the observed assoclatlon constant 1s the sum of the lndlvidual assoc)atlon constants for each mode. Evaluation of the posltlve or negatlve terms of the determinant 1s equivalent to adding together the individual assoclatlon constants for each mode, for qn L or D substrate, respectlvely. Each term to be added 1s expressed as the product of four microconstants. Sixteen mlcroconstants and two bindlng constants represent two equallties, so that If 16 of these values are known, the other two can be determlned. The mlcroconstants for the placement of a pchioroanlline
N-Acetyl p-Hydroxybenzyl p-Chlorocarboxanilide ir-H
3 67 108
Subsite on enzyme Side Leaving chain grow
0 727 63 3 x
0 826
moiety of Kacetyltyrosine pchloroanilide in the side-chain and leavinggroup subsites are calculated from the following determinant.
References and Notes
N-Acyl amino
(1)This work was supported by a Public Health Service Research Career Development Award (l-K4-GM-l0010-02) from the National institute for General Medical Sciences and by a grant (DE-03246) from the National Institutes of Health. (2)(a) M. Caplow, J. Am. Chem. Soc., 91,3639 (1969);(b) E. C.Lucas and M. Caplow, /bid., 94,960 (1972);(c) A. R. Fersht and Y. Requena. /bid.. 93, 7079 (1971);(d) E. C. Lucas, M. Caplow. and K. J. Bush, ibid., 95,
2670 (1973). (3)M. H. O'Leary and M. D. Kiuetz, J. Am. Chem. SOC.,94, 3565 (1972). (4)A. R. Fersht and Y. Requena, J. Mol. Bioi., 60,279 (1971). (5) Abbreviatlons used are HCD-Phe-NH2, Kformyl-L-phenylalanine amide; HCO-D-Phe-NH2, Kformyl-o-phenylalanine amide; HCO-Phe-FH, Kformyi-L-phenylalanine formylhydrazide; HCO-D-Phe-FH, Kformyl-D-phenylalanine formylhydrazlde; HCO-MePhe-FH, Kformyl-Kmethyl-L-phenyialanine formylhydrazide; Ac-Tyr-NHPhCl, Kacetyl-L-tyroslne pchloroanilide; Ac-D-Tyr-NHPhCI, Kacetyl-D-tyrosine pchioroaniiide; AcMeTyr-NHPhCI, Kacetyl-Kmethyl-L-tyrosine pchloroanilide. (6) K. R. Hanson. R. Llna. and E. Havir. 8iochem. BioDhvs. . . Res. Commun.. 29, 194 (1967). (7)S.A. Bernhard, W. C. Coles, and J. F. Nowell, J. Am. Chem. SOC.,82,
3043 (1960). (8)(a) L. W. Cunningham and C. S.Brown, J. 8loi. Chem., 221, 287 (1956); (b) E. Zeeberg, M. Caswell, and M. Caplow, J. Am. Chem. Soc., 95,
2734 (1973). (9)Dr. G, L. Schmlr has calculated an equilibrlum constant equal to 3 X for formlng a neutral tetrahedral Intermediate In the nonenzymatic Intramolecular cycllzatlon of 4-hydroxybutyranlllde (prlvate cornmunhatlon). (10)(a) A. Ruhlman, D. Kukla, P. Schwager, K. Bartels, and R. Huber, J. Mol. Biol, 77, 417 (1973);(b) R. M. Sweet, H. T. Wrlght, J. Janln, C. H. Chothla, and D. M. Blow, Biochem/stry, 13, 4212 (1974). (11) (a) C. L. Hamilton, C. Nlemann, and 0. S. Hammond, Prococ. Net/. Aced. Sci. U.S.A., 55, 684 (1966).(b) Nlemann's determlnant formulation 1s based on the Idea that for multlple mutually exclusive bindlng modes, the observed assoclatlon constant 1s the sum of the lndlvidual assoc)atlon constants for each mode. Evaluation of the posltlve or negatlve terms of the determinant 1s equivalent to adding together the individual assoclatlon constants for each mode, for qn L or D substrate, respectlvely. Each term to be added 1s expressed as the product of four microconstants. Sixteen mlcroconstants and two bindlng constants represent two equallties, so that If 16 of these values are known, the other two can be determlned. The mlcroconstants for the placement of a pchioroanlline
N-Acetyl p-Hydroxybenzyl p-Chlorocarboxanilide ir-H
3 67 108
Subsite on enzyme Side Leaving chain grow
0 727 63 3 x
0 826
