Method of forming N-protected amino acid thiohydantoins

Details Method of forming N-protected amino acid thiohydantoins Method of forming N-protected amino acid thiohydantoins

1992-07-15

1994-04-19

Housel, James C.

Chemistry: analytical and immunological testing

Peptide, protein or amino acid

Amino acid or sequencing procedure

530345, 530334, 07K 102, C07K 102

Patent

active

053044975

ABSTRACT:
A method of forming a thiohydantoin from an N-protected amino acid. The method employs a uronium or phosphonium compound to activate the terminal carboxyl group of the amino acid and a thiocyanate reagent to cyclize the activated amino acid to the thio-hydantoin. The thiohydantoin can be cleaved from its N-protecting group, for use in C-terminal peptide sequencing. Particularly preferred uronium compounds include salts of 2-chlorouronium. Preferred thiocyanate reagents include trimethylsilyl isothiocyanate and crown ether adducts of metallothiocyanates, such as the 18-crown-6 adduct of KSCN.

REFERENCES:
patent: 4173563 (1979-11-01), Yamazaki et al.
patent: 4837165 (1989-06-01), Hawke
patent: 4935494 (1990-06-01), Miller
patent: 4965343 (1990-10-01), Felix et al.
Bannwarth, W., and Knorr, R., "Formation of Carboxamides with N,N,N',N'-Tetramethyl (Succinimido) Uronium Tetrafluoroborate in Aqueous Organic Solvent Systems," Tetrahedron Letters 32(9):1157-1160 (1991).
Dourtoglou, V., and Gross, B., "O-Benzotriazolyl-N,N,N',N'-Tetramethyluronium Hexafluorophosphate as Coupling Reagent for the Synthesis of Peptides of biological Interest," Synthesis 7:572-574 (1984).
Frerot, E., et al., "PyBOP.RTM. and PyBroP: Two Reagents for the Difficult Coupling of the .alpha.,.alpha.-Dialkyl Amino Acid, Aib.," Tetrahedron 47(2):259-270 (1991).
Hawke, D. H., et al., "Microsequence Analysis of Peptides and Proteins: Trimethylsilylisothiocyanate as a Reagent for COOH-Terminal Sequence Analysis," Anal. Biochem. 166:298-307 (1987).
Inglis, A. S., et al., "C-Terminal Sequencing: A New Look at the Schlack-Kumpf Thiocyanate Degradation Procedure," in Methods in Protein Sequence Analysis (Wittman-Liebold, B., ed.) Springer Verlag, 137-144 (1988).
Knorr, et al., "New Coupling Reagent in Peptide Chemistry," Tetrahedron Letters 30(15):1927-1930 (1989).
Meuth, J. L., et al., "Stepwise Sequence Determination from the Carboxyl Terminus of Peptides," Biochem. 21:3750-3757 (1982).
Miller, C. G., "Carboxyl-Terminal Sequence Analysis of Proteins and Peptides by Chemical Methods," in Methods in Protein Sequence Analysis (Wittmann-Liebold, B., ed.) Springer Verlag, 145-151 (1988).
Parham, M. E., and Loudon, G. M., "Carboxyl-Terminal Sequential Degradation of Peptides," Biochem. Biophys. Res. Comm. 80(1):1-6 (1978).
Stark, G. R., "Sequential Degradation of Peptides and Proteins from Their COOH Termini with Ammonium Thiocyanate and Acetic Anhydride," in Methods in Enzymology (Hirs, C. H. W., et al., eds.), Academic Press, vol. 25, 369-384 (1972).
Tarr, G. E., "The Long Search for a Viable Method of C-Terminal Sequencing," in Methods in Protein Sequence Analysis (Wittman Liebold, B., ed.), Springer Verlag, 129-136 (1988).

Affiliated with

Also associated with

Rating

Method of forming N-protected amino acid thiohydantoins does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Method of forming N-protected amino acid thiohydantoins, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method of forming N-protected amino acid thiohydantoins will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-19384