期刊
BIOSENSORS & BIOELECTRONICS
卷 94, 期 -, 页码 657-662出版社
ELSEVIER ADVANCED TECHNOLOGY
DOI: 10.1016/j.bios.2017.03.067
关键词
Peptide probe; Surface plasmon resonance imaging; Sequence-sensitive; Serum albumin; Dual-targeted interaction
类别
资金
- National Natural Science Foundation of China [21375134, 21475140, 21675161, 21621062]
- Ministry of Science and Technology of China [2015CB856303]
- Chinese Academy of Sciences
Peptide-protein interactions mediate numerous biologic processes and provide great opportunity for developing peptide probes and analytical approaches for detecting and interfering with recognition events. Molecular interactions usually take place on the heterogeneous surface of proteins, and the spatial distribution and arrangement of probes are therefore crucial for achieving high specificity and sensitivity in the bioassays. In this study, small linear peptides, homogenous peptide dimers and hetero bivalent peptides were designed for site specific recognition of human serum albumin (HSA). Three hydrophilic regions located at different subdomains of HSA were chosen as targets for the molecular design. The binding affinity, selectivity and kinetics of the candidates were screened with surface plasmon resonance imaging (SPRi) and fluoroimmuno assays. Benefiting from the synergistic effect from the surface-targeted peptide binders and the flexible spacer, a heterogenetic dimer peptide (heter-7) with fast binding and slow dissociation behavior was identified as the optimized probe. Heter-7 specifically recognizes the target protein HSA, and effectively blocks the binding of antibody to HSA. Its inhibitory activity was estimated as 83 nM. It is noteworthy that heter-7 can distinguish serum albumins from different species despite high similarities in sequence and structure of these proteins. This hetero bivalent peptide shows promise for use in serum proteomics, disease detection and drug transport, and provides an effective approach for promoting the affinity and selectivity of ligands to achieve desirable chemical and biological outcomes.
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