Method for producing compound containing heterocycle
AssigneeThe University of Tokyo
InventorsHiroaki Suga, Yuki Goto, Shotaro Tsunoda
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Abstract
An object of the present invention is to provide a method of stably introducing a heterocycle into a substrate peptide by using an azoline backbone introducing enzyme. The present invention provides a method of introducing a heterocycle into a leader-sequence-free substrate peptide by using an azoline backbone introducing enzyme to which a leader sequence of the substrate has been bound.
Claims25
A method for producing a compound having a heterocycle introduced by an azoline backbone introducing enzyme comprising:
- preparing a peptide represented by the following formula (I):
- (Xaa2)m-(Xaa3)n-(Xaa4)o (I)
- wherein,
- (Xaa2)m represents m numbers of arbitrary amino acids and m represents an integer selected from 0 to 10;
- (Xaa3)n represents n numbers of arbitrary amino acids, at least one of which is an amino acid selected from the group consisting of Cys, Ser, Thr, 2,3-diamino acids, homocysteine, homoserine, and 2,4-diamino acids, and analogs thereof, and n represents an integer selected from 2 to 40;
- and
- (Xaa4)o represents o numbers of arbitrary amino acids and o represents an integer selected from 0 to 10, and
- reacting the peptide with an azoline backbone introducing enzyme to which a leader sequence of a substrate or a partial sequence thereof has been bound to introduce a heterocycle into at least one of Cys, Ser, Thr, 2,3-diamino acids, homocysteine, homoserine, and 2,4-diamino acids, and analogs thereof of (Xaa3)n,
- wherein the leader sequence of a substrate or the partial sequence thereof has been bound to the N terminal of the azoline backbone introducing enzyme.
A method for producing a compound having a heterocycle introduced by an azoline backbone introducing enzyme comprising:
- preparing a peptide represented by the following formula (I):
- (Xaa2)m-(Xaa3)n-(Xaa4)o (I)
- wherein
- (Xaa2)m represents m numbers of arbitrary amino acids and m represents an integer selected from 0 to 10;
- (Xaa3)n represents n numbers of arbitrary amino acids, at least one of which is an amino acid selected from the group consisting of Cys, Ser, Thr, 2,3-diamino acids, homocysteine, homoserine, and 2,4-diamino acids, and analogs thereof, and n represents an integer selected from 2 to 40;
- and
- (Xaa4)o represents o numbers of arbitrary amino acids and o represents an integer selected from 0 to 10, and
- reacting the peptide with an azoline backbone introducing enzyme to which a leader sequence of a substrate or a partial sequence thereof has been bound to introduce a heterocycle into at least one of Cys, Ser, Thr, 2,3-diamino acids, homocysteine, homoserine, and 2,4-diamino acids, and analogs thereof of (Xaa3)n,
- wherein the peptide represented by the formula (I) contains an amino acid used for cyclization,
- wherein the peptide represented by the formula (I) contains an amino acid having any of functional groups belonging to the following Functional group 1 and an amino acid having a functional group corresponding thereto in the following Functional group 2:
- TABLE 1
- Functional group 1
- Functional group 2
- (A)
- HS— (A-2)
- (B)
- —C≡C—H (B-1)
- N3— (B-2)
- (C)
- —Ar—CH2NH2 (C-1)
- (D)
- —C≡C—CH2—X1 (D-1)
- HS— (D-2)
- (E)
- —Ar—CH2—X1 (E-1)
- HS— (E-2)
- wherein, X1 represents Cl, Br, or I and Ar represents a substituted or unsubstituted aromatic ring.
Dependencies are inferred from the claim text.