Cyclic peptide, affinity chromatography support, labeled antibody, antibody drug conjugate, and pharmaceutical preparation

Patent metadata

Field	Value
Publication number	US-2018230184-A1
Application number	US-201815949769-A
Country	US
Kind code	A1
Filing date	Apr 10, 2018
Priority date	Oct 23, 2015
Publication date	Aug 16, 2018
Grant date	—

Abstract

Provided is a cyclic peptide, which is represented by Formula (I) or Formula (I′) and has excellent antibody binding properties and improved chemical resistance, an affinity chromatography support, a labeled antibody, an antibody drug conjugate, and a pharmaceutical preparation.
R N -X g -[X i -X a -X m -X 2 -X 3 -X n -X b -X j ] k -X h -R C   (I)

In Formula (I), X a and X b each independently represent an amino acid residue derived from an amino acid, other than L-cysteine and D-cysteine, having a thiol group on a side chain and are bonded to each other through a disulfide bond, or, one of X a and X b represents an amino acid residue derived from an amino acid, other than L-cysteine and D-cysteine, having a thiol group on a side chain and the other represents an amino acid residue derived from an amino acid having a haloacetyl group on a side chain, and X a and X b are bonded to each other through a thioether bond.
R N -X g -[X i -X a -X m -X 1 -X 2 -X 3 -X n -X b -X j ] k -X h -R C   (I′)

In Formula (I′), one of X a and X b represents an amino acid residue derived from L-cysteine or D-cysteine and the other represents an amino acid residue derived from an amino acid having a haloacetyl group on a side chain, and X a and X b are bonded to each other through a thioether bond, or, one of X a and X b represents an amino acid residue derived from L-penicillamine or D-penicillamine and the other represents an amino acid residue derived from an amino acid having a haloacetyl group on a side chain, and X a and X b are bonded to each other through a thioether bond.

First claim

What is claimed is:

1 . A cyclic peptide represented by Formula (I),
R N -X g -[X i -X a -X m -X 2 -X 3 -X n -X b -X j ] k -X h -R C   (I):
in Formula (I), R N represents an N-terminal group; R C represents a C-terminal group; X 1 represents an L-leucine residue, an L-isoleucine residue, an L-methionine residue, an L-lysine residue, or an L-arginine residue; X 2 represents an L-valine residue or an L-isoleucine residue; X 3 represents an L-tryptophan residue; X a and X b each independently represent an amino acid residue derived from an amino acid, other than L-cysteine and D-cysteine, having a thiol group on a side chain, and are bonded to each other through a disulfide bond, or, one of X a and X b represents an amino acid residue derived from an amino acid, other than L-cysteine and D-cysteine, having a thiol group on a side chain, and the other represents an amino acid residue derived from an amino acid having a haloacetyl group on a side chain, and X a and X b are bonded to each other through a thioether bond; X g , X h , X i , X j , X m , and X n each represent g consecutive X's, h consecutive X's, i consecutive X's, j consecutive X's, m consecutive X's, and n consecutive X's; X represents an amino acid residue, and in a case where there is a plurality of X's, the plurality of X's may be the same as or different from each other; g, h, i, and j each independently represent an integer equal to or greater than 0; m and n are integers satisfying 0≤m≤9, 0≤n≤9, and 3≤m+n≤9 simultaneously; and k is an integer equal to or greater than 1, and in a case where k≤2, X 1 , X 2 , X 3 , X a , X b , X i , X j , X m , and X n in a repeating unit [X i -X a -X m -X 1 -X 2 -X 3 -X n -X b -X j ] each may be the same or different between the repeating units.

2 . The cyclic peptide according to claim 1 that is represented by Formula (IA),
R N -X g -[X p2 -X 4 r -X p1 -X a -X m -X 1 -X 2 -X 3 -X n -X b -X q1 -X 5 s -X q2 ] k -X h -R C   (IA):

in Formula (IA),
R N , R C , X 1 , X 2 , X 3 , X a , X b , X g , X h , X m , X n , X, g, h, m, n, and k have the same definitions as those in Formula (I);
X 4 r , X 5 s , X p1 , X p2 , X q1 , and X q2 each represent r consecutive X 4 's, S consecutive X 5 's, p1 consecutive X's, p2 consecutive X's, q1 consecutive X's, and q2 consecutive X's;
X 4 and X 5 each independently represent an amino acid residue derived from an amino acid having a carboxy group on a side chain or an amino acid residue derived from an amino acid having a hydroxy group on a side chain, and in a case where there is a plurality of X 4 's or X 5 's, the plurality of X 4 's or X 5 's may be the same as or different from each other;
p1, p2, q1, and q2 each independently represent an integer equal to or greater than 0;
r and s each represent an integer satisfying 0≤r≤5, 0≤s≤5, and 1≤Max (r,s)≤5,
where Max (r,s) represents a larger one between two numbers represented by r and s in a case where r≠s and represents r or s in a case where r=s; and
in a case where k≥2, X 1 , X 2 , X 3 , X a , X b , X 4 r , X 5 s , X m , X n , X p2 , X p1 , X q1 , and X q2 in a repeating unit [X p2 -X 4 r -X p1 -X a -X m -X 1 -X 2 -X 3 -X n -X b -X q1 -X 5 -X q2 ] each may be the same or different between the repeating units.

3 . The cyclic peptide according to claim 1 that is represented by Formula (IB),
R N -X v1 -X 6 t -X v2 -[X i -X a -X m -X 1 -X 2 -X 3 -X n -X b -X j ] k -X w2 -X 7 u -X w1 -R C   (IB):

in Formula (IB),
R N , R C , X 1 , X 2 , X 3 , X a , X b , X i , X j , X m , X n , X, i, j, m, n, and k have the same definitions as those in Formula (I);
X 6 t , X 7 u , X v1 , X v2 , X w1 , and X w2 each represent t consecutive X 6 's, u consecutive X 7 's, v1 consecutive X's, v2 consecutive X's, w1 consecutive X's, and w2 consecutive X's;
X 6 and X 7 each independently represent an amino acid residue derived from an amino acid having an immobilizing functional group on a side chain, and in a case where there is a plurality of X 6 's or X 7 's, the plurality of X 6 's or X 7 's may be the same as or different from each other;
t and u each represent an integer satisfying 0≤t≤5, 0≤u≤5, and 1≤Max (t,u)≤5,
where Max (t,u) represents a larger one between two numbers represented by t and u in a case where t≠u and represents t or u in a case where t=u;
v1, v2, w1, and w2 each independently represent an integer equal to or greater than 0; and
in a case where k≥2, X 1 , X 2 , X 3 , X a , X b , X i , X j , X m , and X n in a repeating unit [X i -X a -X m -X 1 -X 2 -X 3 -X n -X b -X j ] each may be the same or different between the repeating units.

4 . The cyclic peptide according to claim 1 that is represented by Formula (IC),
R N -X v1 -X 6 t -X v2 -[X p2 -X 4 r -X p1 -X a -X m -X 1 -X 2 -X 3 -X n -X b -X q1 -X 5 s -X q2 ] k -X w2 -X 7 u -X w1 -R C    (IC):

in Formula (IC),
R N , R C , X 1 , X 2 , X 3 , X a , X b , X m , X n , X, m, n, and k have the same definitions as those in Formula (I);
X p1 , X p2 , X q1 , X q2 , X 4 r , X 5 s , X 6 t , X 7 u , X v1 , X v2 , X w1 , and X w2 each represent p1 consecutive X's, p2 consecutive X's, q1 consecutive X's, q2 consecutive X's, r consecutive X 4 's, s consecutive X 5 's, t consecutive X 6 's, u consecutive X 7 's, v1 consecutive X's, v2 consecutive X's, w1 consecutive X's, and w2 consecutive X's′;
X 4 and X 5 each independently represent an amino acid residue derived from an amino acid having a carboxy group on a side chain or an amino acid residue derived from an amino acid having a hydroxy group on a side chain, and in a case where there is a plurality of X 4 's or X 5 's, the plurality of X 4 's or X 5 's may be the same as or different from each other;
X 6 and X 7 each independently represent an amino acid residue derived from an amino acid having an immobilizing functional group on a side chain, and in a case where there is a plurality of X 6 or X 7 , the plurality of X 6 's or X 7 's may be the same as or different from each other;
p1, p2, q1, and q2 each independently represent an integer equal to or greater than 0;
r and s each represent an integer satisfying 0≤r≤5, 0≤s≤5, and 1≤Max (r,s)≤5,
where Max (r,s) represents a larger one between two numbers represented by r and s in a case where r≠s and represents r or s in a case where r=s;
t and u each represent an integer satisfying 0≤t≤5, 0≤u≤5, and 1≤Max (t,u)≤5, where Max (t,u) represents a larger one between two numbers represented by t and u in a case where t≠u and represents t or u in a case where t=u;
v1, v2, w1, and w2 each independently represent an integer equal to or greater than 0; and
in a case where k≥2, X 1 , X 2 , X 3 , X a , X b , X 4 r , X 5 s , X m , X n , X p2 , X p1 , X q1 , and X q2 in a repeating unit [X p2 -X 4 r -X p1 -X a -X m -X 1 -X 2 -X 3 -X n -X b -X q1 -X 5 s -X q2 ] each may be the same or different between the repeating units.

5 . The cyclic peptide according to claim 1 ,
wherein 8≤g+h+k×(i+j+m+n+5)≤50.

6 . The cyclic peptide according to claim 2 ,
wherein 8≤g+h+k×(m+n+p1+p2+q1+q2+5)≤50.

7 . The cyclic peptide according to claim 3 ,
wherein 8≤v1+v2+w1+w2+t+u+k×(i+j+m+n+5)≤50.

8 . The cyclic peptide according to claim 4 ,
wherein 8≤v1+v2+w1+w2+t+u+k×(m+n+p1+p2+q1+q2+5)≤50.

9 . The cyclic peptide according to claim 2 ,
wherein the amino acid having a carboxy group on a side chain is at least one kind of amino acid selected from the group consisting of L-aspartic acid, D-aspartic acid, L-glutamic acid, D-glutamic acid, L-homoglutamic acid, and D-homoglutamic acid, and the amino acid having a hydroxy group on a side chain is at least one kind of amino acid selected from the gr

Assignees

• Fujifilm Corp

Inventors

• Minami Koichi

Classifications

• C07K16/00

  Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies · CPC title

• C07K7/06

  having 5 to 11 amino acids · CPC title

• C07K1/13

  Labelling of peptides · CPC title

• C07K7/54 Primary

  with at least one abnormal peptide link in the ring · CPC title

• A61K39/39525

  Purification · CPC title