Lanthionine bridged peptides

Details Lanthionine bridged peptides Lanthionine bridged peptides

1999-08-26

2001-07-31

Celsa, Bennett (Department: 1627)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Peptide containing doai

C514S014800, C514S015800, C514S016700, C514S017400, C530S302000, C530S307000, C530S315000, C530S317000, C930S050000

Reexamination Certificate

active

06268339

ABSTRACT:

It is a basic goal in peptide chemistry to design molecules for medical or industrial application. Design means that naturally occurring peptides which have a biological activity are modified in order to obtain molecules which have advantages over the naturally occurring peptides in different respects. There are several groups of peptides which act as hormones, as neurotoxins or as plant regulating agents. These peptides are usually small, flexible molecules which may optionally have a disulfide bridge.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide peptides which comprise a monosulfide bridge. This thioether bond is also designated as a lanthionine bridge and corresponds with the cystine bridge with the exception that the disulfide bridge is replaced by a monosulfide linkage. Two amino acid residues having the general formula
are designated to be joined into a lanthionine bridge wherein the linkage of the two amino acids has the meaning —RCH—S—HCR′—, wherein R and R′ respectively represent —H, a lower (C
1
-C
10
) alkyl or aralkyl group. In a preferred embodiment R and R′ are H. The amino acid termini of the lanthionine structure are designated as Ala
L
if R and R′ are H and Thr
L
when R or R′ are CH
3
. Other &bgr;-substituted lanthionine components are designated as substituted Ala
L
derivatives, e.g. &bgr;ethylAla
L
.
DESCRIPTION OF THE RELATED ART
Thioether bonus of the lanthionine type are known from some fungal toxins and antibiotics, for example from the lantibiotics, as nisin, epidermin, dunamycin or mersacidin. Naturally occurring compounds having the monosulfide bridge always have more than two monosulfide bridges in the molecule.
M. F. Bean et al. have reported in their article “Identification of a Thioether By-product in the Synthesis of a Cyclic Disulfide Peptide by Tandem Mass Spectrometry” as published in the Proceedings of the 11th American Peptide Symposium, ESCOM, (Leiden 1990, p. 443) on a somatostatin analog wherein the internal disulfide bond has been converted to a thioether link. The somatostatin analog with the putative amino acid sequence D-Phe-Ala
L
-Phe-Trp-Lys-Thr-Ala
L
-Thr(ol), wherein the two Ala
L
residues are linked via the thioether bridge, has been described as the by-product which was obtained by the Boc-TFA-preparation of sandostatin analogs. The originally occurring somatostatin derivative has a disulfide bridge.


REFERENCES:
patent: 3446789 (1969-05-01), Rudinger et al.
patent: 3980631 (1976-09-01), Procházka et al.
patent: 4148786 (1979-04-01), Sarantakis
patent: 4161521 (1979-07-01), Veber et al.
patent: 4322339 (1982-03-01), Gesellchen et al.
patent: 4349544 (1982-09-01), Cort et al.
patent: 4482486 (1984-11-01), Brtnik et al.
patent: 4483794 (1984-11-01), Barth et al.
patent: 4518711 (1985-05-01), Hruby et al.
patent: 6028168 (2000-02-01), Goodman et al.
patent: 93/03056 (1993-02-01), None
CA: 125:317643q of Lee et al., Pept. 1994 Proc. Eur. Pept. Symp. 23rd 1994 pp. 627-628, 1995.*
CAPLUS AN:1978:417351 to Ling et al., Pept. Proc. Am. Pept. Symp. 5th 96-9, 1995.*
Harpp and Gleason, “Preparation of Mass and Spectral Properties of Cystine and Lathinone Derivatives. A Novel Synthesis at L-Lanthinone by Selective Desulfurization”, Department of Chemistry, McGill University, Montreal, Canada,J. Org. Chem, vol. 36, No. 1, 1971 pp. 73-80.
Hruby, “Minireview, Conformational Restrictions of Biologically Active Peptides via Amino Acid Side Chain Groups”.
Degrado, “Design of Peptides and Proteins” excerpt from “Advances in Protein Chemistry”, vol. 39, pp. 51-67.
Olsen et al. “Conversion of Thiosulfate Derivatives of Cystine to Unsymmetrical Cystines and Lathinones by Reaction with Tris (dialky/amino) phosphines” Department of Chemistry and Biochemistry, Utah State University,J. Org. Chem., 1985, 50, 4332-4336.
Bean, et al., “Identification of a thioether by-product in the synthesis of a cyclic disulfide peptide by tandem mass spectrometry” printed at pp. 443-445 of “Peptides: Chemistry, Structure and Biology”.
Proceedings of the Twenty-Third European Peptide Symposium, “Peptides 1994”, Editor: Hernani L.S.Maia.

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