[Structure-based design, synthesis and evaluation of bioactivity of anti-P-gp peptide mimetic].
OBJECTIVE
To design and evaluate the small peptide mimetic of anti-P-glycoprotein (P-gp) antibody (PHMA02).


METHODS
From the three dementional structure analysis of computer modeling of PHMA02 CDR loops, a small peptide mimetic was designed and determined by flow cytometry.


RESULTS
Anti-P-gp peptide mimetic functionally similar to PHMA02 was developed. The peptide mimetic competitively inhibits PHMA02 binding to P-gp and partially block the P-gp function as a drug efflux pump in K562/A02 cells.


CONCLUSIONS
Some special conformational properties of CDR loops of antibody might serve as lead structures for develop new biological peptide mimetics. Antibody-structure-based design would develop new drug in the future.
Qi
Jing
J
State Key Laboratory of Experimental Hematology, Institute of Hematology, Chinese Academy of Medical Sciences, Peking Union Medical College, Tianjin 300020, China.
Peng
Hui
H
Gao
Ying-dai
YD
Xu
Chen
C
Liang
Zhong-qin
ZQ
Gu
Zhen-lun
ZL
Yang
Chun-zheng
CZ
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry* / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000737:chemistry; D001667:Binding, Competitive; D022801:Complementarity Determining Regions / Q000737:chemistry*; D015195:Drug Design; D018432:Drug Resistance, Multiple; D006801:Humans; D020014:K562 Cells; D018716:Molecular Mimicry; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D022801:Complementarity Determining Regions; D010455:Peptides