US 11,866,470 B2
Polypeptides with phase transition, triblock polypeptides of the polypeptide-calmodulin-polypeptide with multi-stimuli responsiveness, hydrogel of the triblock polypeptides, and its uses
Dong Woo Lim, Ansan-si (KR); Jae Sang Lee, Ansan-si (KR); and Min Jung Kang, Bucheon-si (KR)
Assigned to Industry-University Cooperation Foundation Hanyang University Erica Campus, Ansan-si (KR)
Filed by INDUSTRY-UNIVERSITY COOPERATION FOUNDATION HANYANG UNIVERSITY ERICA CAMPUS, Ansan-si (KR)
Filed on Jun. 8, 2021, as Appl. No. 17/341,465.
Application 17/341,465 is a division of application No. 15/744,210, granted, now 11,059,870, previously published as PCT/KR2016/003658, filed on Apr. 7, 2016.
Claims priority of application No. 10-2016-0030238 (KR), filed on Mar. 14, 2016.
Prior Publication US 2021/0388042 A1, Dec. 16, 2021
Int. Cl. C07K 14/47 (2006.01); A61L 27/22 (2006.01); A61L 27/52 (2006.01); C07K 7/06 (2006.01); C07K 14/78 (2006.01)
CPC C07K 14/47 (2013.01) [A61L 27/22 (2013.01); A61L 27/52 (2013.01); C07K 7/06 (2013.01); C07K 14/78 (2013.01)] 14 Claims
 
1. A triblock polypeptide having multi-stimuli responsiveness, wherein the triblock polypeptide is consisted of
a calmodulin block; and
polypeptide blocks having a phase transition behavior linked to both ends of the calmodulin block, and is represented by Formula 4 below:
[hydrophobic EBP]m-[hydrophilic EBP]x-Cal[hydrophilic EBP]x-[hydrophobic EBP]m, wherein  Formula 4
the [hydrophobic EBP]m refers to a polypeptide block having a phase transition behavior;
the [hydrophobic EBP]m-[hydrophilic EBP]x refers to a polypeptide block having a phase transition behavior;
the hydrophobic EBP is consisted of a hydrophobic polypeptide which is a pentapeptide of Val-Pro-Ala-Xaa-Gly (SEQ ID NO: 2);
the hydrophilic EBP is consisted of a hydrophilic polypeptide which is a pentapeptide of Val-Pro-Ala-Xaa-Gly (SEQ ID NO: 2);
wherein Xaa is a natural amino acid other than proline;
m or x, each respectively, is an integer of 2 or more, and is the number of repeats of the hydrophobic polypeptide and hydrophilic polypepteide having a phase transition behavior;
the CalM is a calmodulin block, wherein an amino acid sequence encoding the calmodulin is SEQ ID NO: 38,
wherein each Xaa of the pentapeptide repeats is consisted of A(Ala), G(Gly), I(Ile); K(Lys), G(Gly), I(Ile); D(Asp), G(Gly), I(Ile); and E(Glu), G(Gly), I(Ile) in a ratio of 1:4:1;
each Xaa of the pentapeptide repeats is consisted of G(Gly), A(Ala), F(Phe); K(Lys), A(Ala), F(Phe); and D(Asp), A(Ala), F(Phe) in a ratio of 1:3:2;
each Xaa of the pentapeptide repeats is consisted of K(Lys) and F(Phe) in a ratio of 3:3;
each Xaa of the pentapeptide repeats is consisted of D(Asp) and F(Phe) in a ratio of 3:3;
each Xaa of the pentapeptide repeats is consisted of H(His), A(Ala), and I(Ile) in a ratio of 3:2:1;
each Xaa of the pentapeptide repeats is consisted of H(His) and G(Gly) in a ratio of 5:1; or
each Xaa of the pentapeptide repeats is consisted of G(Gly), C(Cys), and F(Phe) in a ratio of 1:3:2;
wherein the polypeptide block is further linked a cysteine block with both end of thereof;
wherein the cysteine block is consisted of an amino acid sequence in which (Gly-Ala-Cys) repeats one or more times.