TY  - JOUR
A1  - Mian, Afsar Ali
A1  - Schüll, Marion
A1  - Oancea, Claudia
A1  - Najajreh, Yousef
A1  - Mahajna, Jamal
A1  - Goldblum, Amiram
A1  - Ottmann, Oliver G.
A1  - Beißert, Tim
A1  - Ruthardt, Martin
T1  - Targeting the oligomerization of BCR/ABL by membrane permeable competitive peptides inhibits the proliferation of Philadelphia Chromosome positive leukemic cells
T2  - The open hematology journal
N2  - The BCR/ABL fusion protein is the hallmark of Philadelphia Chromosome positive (Ph+) leukemia. The constitutive activation of the ABL-kinase in BCR/ABL cells induces the leukemic phenotype. Targeted inhibition of BCR/ABL by small molecule inhibitors reverses the transformation potential of BCR/ABL. Recently, we definitively proved that targeting the tetramerization of BCR/ABL mediated by the N-terminal coiled-coil domain (CC) using competitive peptides, representing the helix-2 of the CC, represents a valid therapeutic approach for treating Ph+ leukemia. To further develop competitive peptides for targeting BCR/ABL, we created a membrane permeable helix-2 peptide (MPH-2) by fusing the helix-2 peptide with a peptide transduction tag. In this study, we report that the MPH-2: (i) interacted with BCR/ABL in vivo; (ii) efficiently inhibited the autophosphorylation of BCR/ABL; (iii) suppressed the growth and viability of Ph+ leukemic cells; and (iv) was efficiently transduced into mononuclear cells (MNC) in an in vivo mouse model.
This study provides the first evidence that an efficient peptide transduction system facilitates the employment of competitive peptides to target the oligomerization interface of BCR/ABL in vivo.
KW  - Philadelphia Chromosome-positive leukemia
KW  - BCR/ABL
KW  - molecular targeting
KW  - competitive peptide
KW  - oligomerization
Y1  - 2013
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/28859
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-288599
SN  - 1874-2769
N1  - © Mian et al.; Licensee Bentham Open. This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.
VL  - 5
SP  - 21
EP  - 27
PB  - Bentham Open
CY  - Sharjah
ER  -