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US 2024/0051996 A1Published application
Non-chromatographic purification of macrocyclic peptides by a resin catch and release
AssigneeBristol-Myers Squibb Company
InventorsGardner S. CREECH, Mahboubeh KHEIRABADI, Martin D. EASTGATE, David S. NIRSCHL, Percy H. CARTER
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Abstract
The disclosure is directed to the synthesis and improved methods for purifying macrocyclic peptides produced by solid phase peptide synthesis.
Claims5
A purified macrocyclic peptide produced by a method comprising:
- (a) preparing a resin-bound linear peptide wherein said linear peptide comprises a free amino group and an amino acid residue having a nucleophilic side chain;
- (b) reacting the free amino group of the resin-bound linear peptide with an azide- or alkyne-functionalized cap to form a resin-bound capped linear peptide having an azide- or alkyne-functionalized cap;
- (c) cleaving said capped linear peptide from the resin to form a free capped linear peptide having an azide- or alkyne-functionalized cap;
- (d) reacting the free capped linear peptide having an azide-functionalized cap with an alkyne functionalized catch resin, or reacting the free capped linear peptide having an akynyl-functionalized cap with an azide functionalized catch resin, to form a catch-resin bound capped linear peptide;
- (e) washing the catch-resin bound capped linear peptide;
- and
- (f) reacting the catch-resin bound capped linear peptide under conditions sufficient to effect macrocyclization of the linear peptide and release of the macrocyclic peptide from the catch resin.
4 more elements
A compound of formula (I)
- wherein
- X is a bond, —O—, —C(O)—, —OC(O)—, —NH—, —N(C1-6alkyl)-, —N(aryl)-, —NH—C(O)—, —N(C1-6alkyl)C(O)—, or —N(aryl)C(O)—;
- and
- R1 is
- wherein R2 and R3 are each independently H, halo, C1-6alkyl, or OC1-6alkyl;
- Z is C1-6alk or —O—C1-6alk-;
- and
- Y is a bond or arylene.
5 more elements
A compound of Formula (II):
- wherein the resin is a polyethylene glycol-based or polystyrene-based resin;
- the linker is
- wherein *(denotes the point of attachment of the linker to the resin, and)** denotes the point of attachment of the linker to the catch moiety;
- and the catch moiety is
- wherein Q is —O—, —NH—, or —CH2—
- R2 and R3 are each independently H, halo, C1-6alkyl, or OC1-6alkyl;
- Z is C1-6alk or —O—C1-6alk-;
- and
- Y is a bond or arylene.
6 more elements
Dependencies are inferred from the claim text.