Thermally sensitive protecting groups for cysteine for peptide cyclization and selective disulfide bond formation
OwnerJohn Frederick Trant, Sarah Nasri +5inventors
InventorsJohn Frederick Trant, Sarah Nasri, Maryamalsadat Kosar, Sanaz Nadimi, Mohaddeseh Dashti Nejad Pour, Purshotam Sharma, Seyedeh Maryamdokht Taimoory
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Abstract
In a preferred embodiment, there is provided a protecting group for protecting the thiol side chain of a cysteine residue, the protecting group comprising a Diels-Alder cycloadduct of a furan and a maleimide, and optionally, a linker interposed between the thiol side chain and the Diels-Alder cycloadduct.
Claims25
A protecting group for protecting a cysteine residue, the protecting group having structural formula 11 or 12:
- wherein
- R is an electron withdrawing group or a leaving group;
- Ar is optionally substituted aryl or optionally substituted heteroaryl;
- X, Y, Z and Z1 are independently of each other oxygen, sulfur, nitrogen or phosphorus;
- R1 and R2 are independently of each other hydrogen, hydroxyl, halo, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, formyl, haloformyl, carbonyl, carboxyl, alkoxy, alkoxycarbonyl, (alkoxycarbonyl)oxy, carbamoyl, amino, amido, imino, imido, azo, cyanato, isocyanato, cyano, nitro, sulfanyl, thiocyanato or phosphono, each of which is optionally substituted;
- and
- n and n1 are independently of each other an integer between 1 and 12, inclusive.
A protected cysteine having structural formula 13 or 14:
- wherein
- Ar is optionally substituted aryl or optionally substituted heteroaryl;
- X, Y, Z and Z1 are independently of each other oxygen, sulfur, nitrogen or phosphorus;
- R1 and R2 are independently of each other hydrogen, hydroxyl, halo, alkyl, alkenyl, alkenyl, cycloalkyl, heterocycloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, formyl, haloformyl, carbonyl, carboxyl, alkoxy, alkoxycarbonyl, (alkoxycarbonyl)oxy, carbamoyl, amino, amido, imino, imido, azo, cyanato, isocyanato, cyano, nitro, sulfanyl, thiocyanato or phosphono, each of which is optionally substituted;
- R3 and R4 are independently each other hydrogen or a protecting group;
- and
- n and n1 are independently of each other an integer between 1 and 12, inclusive.
A compound having structural formula 15 or 16:
- wherein
- R is an electron withdrawing group or a leaving group;
- X and Y are independently of each other oxygen, sulfur, nitrogen or phosphorus;
- R1 and R2 are independently of each other hydrogen, hydroxyl, halo, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, formyl, haloformyl, carbonyl, carboxyl, alkoxy, alkoxycarbonyl, (alkoxycarbonyl)oxy, carbamoyl, amino, amino, imino, imido, azo, cyanato, isocyanato, cyano, nitro, sulfanyl, thiocyanato or phosphono, each of which is optionally substituted;
- and
- n is an integer between 1 and 12, inclusive.
Dependencies are inferred from the claim text.