[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.
State Key Laboratory of Experimental Hematology, Institute of Hematology, Chinese Academy of Medical Sciences, Peking Union Medical College, Tianjin 300020, China.
Jing
J
Qi
Hui
H
Peng
Ying-dai
YD
Gao
Chen
C
Xu
Zhong-qin
ZQ
Liang
Zhen-lun
ZL
Gu
Chun-zheng
CZ
Yang
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