Patent ID: 11884713
Assignee: ZEALAND PHARMA A/S
Field: Pharmaceuticals (Chemistry)
Classification: CPC C  A  Y | IPC A  C

Claim 1:
2. A method of producing a compound having the formula:

R1—P1—P2—R2 

wherein
R1 is H, C1-4 alkyl, acetyl, formyl, benzoyl or trifluoroacetyl;
R2 is OH or NH2;
P1 is a peptide having the sequence:

His-X2-X3-GTFTSDYSKYL-X15-X16-X17-X18-A-X20-DFI-X24-WLE-X28-A

wherein:
X2 is selected from Aib, Ac3c, Ac4c and Ac5c;
X3 is selected from Gln and His;
X15 is selected from Asp and Glu;
X16 is selected from Glu and ψ;
X17 is selected from Arg and ψ;
X18 is selected from Ala and Arg;
X20 is selected from Lys and His;
X24 is selected from Glu and ψ; and
X28 is selected from Ser and ψ;
and P2 is absent or is a sequence of 1-20 amino acid units independently selected from the group consisting of Ala, Leu, Ser, Thr, Tyr, Cys, Glu, Lys, Arg, Dbu, Dpr and Orn;
wherein the compound contains one and only one ψ,
and wherein said ψ is a residue of Lys, Arg, Orn or Cys in which the side chain is conjugated to a substituent having the formula —Z2Z1;
—Z1 is a fatty chain having a polar group at one end of the chain and a connection to Z2, —X— at the end of the chain distal from the polar group,
wherein the polar group comprises a carboxylic acid or a carboxylic acid bioisostere, a phosphonic acid, or a sulfonic acid group;
and —X— is a bond, —CO—, —SO—, or —SO2—;
—Z2— is a spacer of formula:, wherein:
each Y is independently —NH, —NR, —S or −0, where R is alkyl, a protecting group or forms a linkage to another part of the spacer Z2;
each X is independently a bond, CO—, SO—, or SO2—;
with the proviso that when Y is —S, X is a bond;
each V is independently a bivalent organic moiety linking Y and X;
and n is 1-10;
the method comprising expressing a precursor peptide sequence from a nucleic acid construct that encodes the precursor peptide, recovering the expression product, and modifying the precursor peptide to yield the compound.