US 12,329,799 B2
Peptidyl inhibitors of calcineurin-NFAT interaction
Dehua Pei, Columbus, OH (US); John W. Christman, Columbus, OH (US); Manjula Karpurapu, Columbus, OH (US); and Patrick G. Dougherty, Columbus, OH (US)
Assigned to Ohio State Innovation Foundation, Columbus, OH (US)
Filed by Ohio State Innovation Foundation, Columbus, OH (US)
Filed on Feb. 1, 2023, as Appl. No. 18/104,643.
Application 18/104,643 is a division of application No. 16/965,718, granted, now 11,576,946, previously published as PCT/US2019/015695, filed on Jan. 29, 2019.
Claims priority of provisional application 62/623,235, filed on Jan. 29, 2018.
Prior Publication US 2024/0033318 A1, Feb. 1, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 38/08 (2019.01); A61K 47/64 (2017.01); A61P 11/00 (2006.01)
CPC A61K 38/08 (2013.01) [A61K 47/64 (2017.08); A61P 11/00 (2018.01)] 20 Claims
 
1. A polypeptide conjugate, comprising Formula I, II, or III

OG Complex Work Unit Chemistry
wherein:
each of AA1, AA2, AA3, AA4, AAL and AAz are independently an amino acid which is optionally substituted;
n is an integer from 0 to 6;
M is a bonding moiety;
L is a linking moiety comprising at least one amino acid, alkylene, β-Ala-Lys or combinations thereof, each of which are optionally substituted;
each of AAU1, AAU2, AAU3, AAU4, AAU5 and AAU6, is optional and independently selected from an amino acid which is optionally substituted;
calcineurin (CN) binding motif (CNBM) comprises a sequence selected from the group consisting of:
(i)
(SEQ ID NO: 1)
Tle-Ile-Tle-Ile-Thr (ZIZIT);
 
(ii)
(SEQ ID NO: 2)
Val-Ile-Val-Ile-Thr (VIVIT);
 
(iii)
 (SEQ ID NO: 3)
Val-Ile-Tle-Ile-Thr (VIZIT);
 
(iv)
(SEQ ID NO: 4)
Tle-Ile-Hva-Ile-Thr;
 
(v)
(SEQ ID NO: 5)
 
Tle-Ile-Val-Ile-Thr (ZIVIT);
 
(vi)
(SEQ ID NO: 6)
Tle-Ile-Bhv-Ile-Thr;
 
(vii)
(SEQ ID NO: 7)
Tle-Chg-Bhv-Ile-Thr ;
 
(viii)
(SEQ ID NO: 8)
Tle-Ile-Psa-Ile-Thr ;
or
 
(ix)
(SEQ ID NO: 9)
Tle-Chg-Psa-Ile-Thr;
RH is a hydrophobic non-peptidyl moiety which interacts with the hydrophobic pocket in a CN protein;
wherein:
at least two of AA1, AA2, AA3, AA4, and AAz are arginines; and
at least two of AA1, AA2, AA3, AA4, and AAz are independently amino acids having a hydrophobic side chain.