Acidic derivatives of homocysteine thiolactone

Details Acidic derivatives of homocysteine thiolactone Acidic derivatives of homocysteine thiolactone

1992-10-15

1993-12-28

Raymond, Richard L.

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

549 63, 549321, 530404, C07D33336

Patent

active

052741222

ABSTRACT:
Homocysteine thiolactone derivatives in which the nitrogen is acylated with groups containing acidic functionalities have been synthesized. These include the succinyl, the carboxymethylglutaryl, the 3-phosphonopropionyl and the 3-sulfopropionyl derivatives. These thiolactones can be used to introduce a thiol functionality into proteins such as the outer membrane protein complex of Neisseria meninioitidis (OMPC) allowing conjugation with electrophilic ligands. This chemistry is similar to known N-acetyl-homocysteine thiolactone chemistry, but the pK.sub.a values are such that at pH 7, concomitant negative charge is introduced into the conjugate. Such negative charge neutralizes excess positive charge introduced when arginine- and lysine-rich peptides are bonded as ligands. In the case of OMPC, introduction of positive charge commonly effects irreversible precipitation of the conjugate. Conjugates prepared with the anionic thiolactones have improved solubility.

REFERENCES:
patent: 4072703 (1978-02-01), Blum
patent: 4271147 (1981-01-01), Helting et al.
patent: 4411909 (1983-10-01), Gonella
patent: 4690944 (1987-09-01), Chiesi et al.
patent: 4691006 (1987-09-01), Stevens
patent: 4695624 (1987-09-01), Marburg
patent: 4762913 (1988-08-01), Stevens
patent: 4767842 (1988-08-01), Stevens
patent: 4902506 (1990-02-01), Anderson et al.
patent: 4956273 (1990-09-01), Kennedy et al.
patent: 5013548 (1991-05-01), Haynes et al.
patent: 5017688 (1991-05-01), Gilbert et al.
patent: 5019387 (1991-05-01), Haynes et al.
Javaherian, et al., PNAS USA 86,6768 (1989).
Marburg, et al., JACS 108, 5282 (1986), Marburg, Ill.
Palker, et al., PNAS USA 85, 1932 (1988), Palker I.
Palker, et al., J. Immunol., 142, 3612 (1989), Palker II.
Blair, et al., J. Imm. Methods, 59:129-143 (1983).
Devash, et al., PNAS 87: 3445-3449 (1990).
Fauci PNAS 83: 9278-9283 (1986).
Goudsmit, et al., Res. Virol. 140: 419-436 (1986).
Rudinger in J. A. Parsons ed Peptide Hormones, pp. 1-7 University Park Press Baltimore (1976).
Emini, et al., Nature, vol. 20, pp. 728-730 (1992).
Matsushita, et al., J. of Virol., 62, No. 6 pp. 2107-2114 (1988).
Emini et al., J. of Virol., 64, No. 8, pp. 3674-3678 (1990).
Helting, et al., Act path. microbiol.scand. 89, pp. 69-78 (1981).
Girard, et al., Proc. Natl. Acad. Sci. USA, 88, pp. 542-546 (1991).
Biberfield & Emini, AIDS, 5, (Suppl. 2), pp. S129-S133 (1991).
Goudsmit, et al., P.N.A.S. 85: 4478-4482 (1988).
Rusche, et al., P.N.A.S. 85: 3198-3202 (1988).
Frasch, C. and Robbins, J., J. Exp. Med. 147: 629-644 (1978).
Barnes, D., Research News 240: 719-721 (1988).
Hilleman, M., Vaccine 6: 175-179 (1988).
Frasch, C. and Gotschlich, E. J. Exp. Med. 140: 87-104 (1974).
Putney, S., et al., Chem. Abst. 110:89579f, p. 162 (1988).
Fujii, N., et al., Int. J. Pep. Prot. Res. 26: 121-129 (1985).
Robertson, G. et al., J. Virol. Meth. 20:195-202 (1988).
Klotz, I. M. & Heiney, R. E., J. Am. Chem. Soc. 81:3802-3 (1959).
LaRosa, et al., Science 249:932-935 (1990).
Sandstrom & Kaplan, Drugs 34: 372-390 (1987).
Lowell, G. et al., J. Exper. Med. 167: 658-663 (1988).
Lowell, G. et al., Tech. Adv. in Vaccine Dev., 423-432 (1988).

Affiliated with

Also associated with

Rating

Acidic derivatives of homocysteine thiolactone does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Acidic derivatives of homocysteine thiolactone, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Acidic derivatives of homocysteine thiolactone will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1544148