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US3988307A
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US
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Solid phase synthesis of peptides with carboxyl-terminal amides
Assignee: United States Department of Health and Human Services
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Filing: 1974-09-06
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Granted: 1976-10-26
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Expires: 1994-09-06
Abstract
Abstract The method of utilizing alpha , beta -unsaturated amino acids, acyl, and N-acyl derivatives as linking agents in the solid phase synthesis of peptides with the corresponding production of carboxyl terminal amides. Preferred unsaturated amino acids are dehydroalanine and dehydrobutyrine which are constituents in naturally occurring amides such as nisin and subtilin. The synthesis follows conventional lines of R. B. Merrifield et al including blocking of the amino nitrogen, with the exception that the release agent contains an amount of water equimolar to the reactant alpha , beta -unsaturated amino acid.
Inventors
- 👤 Erhard Gross
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-01 19:49
CPC Classifications
C; C07; C07K; C07K5/00; C07K5/04; C07K5/06; C07K5/06139; C07K5/06165; C07K1/00; C07K1/003; C07K5/08; C07K5/0802; C07K5/0804; C07K5/0808; C07K5/10; C07K5/1002; C07K5/1005; C07K5/101; Y; Y10; Y10S; Y10S930/00; Y10S930/01; Y10S930/28
Claims Analysis
Total Claims: 11
Claim 1
Independent Claim
94 words
A method of synthesizing peptides by solid phase procedure which comprises attaching an α,β-unsaturated amino acid through the teriminal carboxyl group to a solid insoluble support with the α-nitrogen blocked by a protecting group and subsequently unblocking the α-nitrogen by removing said protecting group and growing the peptide chain on said support by sequentially adding amino acids conforming to the desired peptide sequence and adding an acidic aqueous release solution to said peptide and support to convert the α,β-unsaturated amino acid to a carboxyl terminal amide and releasing said amide from said solid support.
Claim 2
Independent Claim
94 words
A method of synthesizing peptides by solid phase procedure which comprises attaching an α,β-unsaturated amino acid through the teriminal carboxyl group to a solid insoluble support with the α-nitrogen blocked by a protecting group and subsequently unblocking the α-nitrogen by removing said protecting group and growing the peptide chain on said support by sequentially adding amino acids conforming to the desired peptide sequence and adding an acidic aqueous release solution to said peptide and support to convert the α,β-unsaturated amino acid to a carboxyl terminal amide and releasing said amide from said solid support.
Claim 3
Dependent Claim
25 words
The method according to claim 1 wherein the aqueous release solution contains an amount of water equimolar to the amount of α,β-unsaturated amino acid utilized.
Claim 4
Dependent Claim
22 words
The method according to claim 1 wherein the aqueous release solution is a mixture of 1 N HCl in glacial acetic acid.
Claim 5
Dependent Claim
98 words
The method according to claim 1 used for the synthesis of pyroglutamylhistidylproline amide (Thyrotropin-releasing factor; TRF) by a. attaching Boc-prolyldehydroalanine to the solid support; b. removing the Boc-group by treatment with 25% TFA in CH 2 Cl 2 ; c. attaching Boc-histidine and Boc-pyroglutamic acid via solid phase techniques of peptide synthesis using dicyclohexylcarbodiimide as activating agent and removing the Boc-group from histidine by treatment with 25% TFA in CH 2 Cl 2 ; d. removing pyroglutymylhistidylproline amide (TRF) from the solid support by treatment with one equivalent of water in 1 N HCl in glacial acetic acid.
Claim 6
Dependent Claim
12 words
The method according to claim 1 wherein the protecting group is Boc.
Claim 7
Dependent Claim
13 words
The method according to claim 1 wherein the support is chloromethylated styrene/DVB copolymer.
Claim 8
Dependent Claim
13 words
The method according to claim 1 wherein the support is hydroxymethylated styrene/DVB copolymer.
Claim 9
Dependent Claim
30 words
The method according to claim 1 wherein the α,β-unsaturated amino acid is selected from the group consisting of dehydroalanine, dehydrobutyrine (β-methyldehydroalanine), dehydroserine, dehydroleucine, dehydrophenylalanine, dehydrotryptophan, dehydroarginine, dehydroproline, dehydrovaline, and dehydrocysteine.
Claim 10
Dependent Claim
13 words
The method according to claim 8 wherein the α,β-unsaturated amino acid is dehydroalanine.
Claim 11
Dependent Claim
13 words
The method according to claim 8 wherein the α,β-unsaturated amino acid is dehydrobutyrine.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1979-10-26 | 1980-04-26 | 1980-10-26 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1983-10-26 | 1984-04-26 | 1984-10-26 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1987-10-26 | 1988-04-26 | 1988-10-26 | $7700.00 | Window Closed / Lapsed |