Dataset Information

PDL1Binder: Identifying programmed cell death ligand 1 binding peptides by incorporating next-generation phage display data and different peptide descriptors.

ABSTRACT: Monoclonal antibody drugs targeting the PD-1/PD-L1 pathway have showed efficacy in the treatment of cancer patients, however, they have many intrinsic limitations and inevitable drawbacks. Peptide inhibitors as alternatives might compensate for the drawbacks of current PD-1/PD-L1 interaction blockers. Identifying PD-L1 binding peptides by random peptide library screening is a time-consuming and labor-intensive process. Machine learning-based computational models enable rapid discovery of peptide candidates targeting the PD-1/PD-L1 pathway. In this study, we first employed next-generation phage display (NGPD) biopanning to isolate PD-L1 binding peptides. Different peptide descriptors and feature selection methods as well as diverse machine learning methods were then incorporated to implement predictive models of PD-L1 binding. Finally, we proposed PDL1Binder, an ensemble computational model for efficiently obtaining PD-L1 binding peptides. Our results suggest that predictive models of PD-L1 binding can be learned from deep sequencing data and provide a new path to discover PD-L1 binding peptides. A web server was implemented for PDL1Binder, which is freely available at http://i.uestc.edu.cn/pdl1binder/cgi-bin/PDL1Binder.pl.

SUBMITTER: He B

PROVIDER: S-EPMC9335124 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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PDL1Binder: Identifying programmed cell death ligand 1 binding peptides by incorporating next-generation phage display data and different peptide descriptors.

He Bifang B Li Bowen B Chen Xue X Zhang Qianyue Q Lu Chunying C Yang Shanshan S Long Jinjin J Ning Lin L Chen Heng H Huang Jian J

Frontiers in microbiology 20220715

Monoclonal antibody drugs targeting the PD-1/PD-L1 pathway have showed efficacy in the treatment of cancer patients, however, they have many intrinsic limitations and inevitable drawbacks. Peptide inhibitors as alternatives might compensate for the drawbacks of current PD-1/PD-L1 interaction blockers. Identifying PD-L1 binding peptides by random peptide library screening is a time-consuming and labor-intensive process. Machine learning-based computational models enable rapid discovery of peptide ...[more]

PMID: 35910615

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Project description:PURPOSE:Osteosarcoma represents the most common malignant primary bone tumor in childhood; however, the survival rate has remained unchanged for the past 20 years. To improve existing diagnosis and treatment methods and broaden the spectrum of imaging agents that can be used for early detection and assessment of tumor response to therapy, we performed a phage display-based screening for peptide sequences that bind specifically to osteosarcoma cells. EXPERIMENTAL DESIGN:From the Ph.D.-12 phage display peptide library composed of 2.7 x 10(9) different displayed peptides, one peptide was enriched after four rounds of in vitro selection in 143B osteosarcoma tumor cells with 293T human embryonic kidney cells as a control. Both the peptide and the phage clone displaying the peptide were conjugated with fluorescent dyes for in vitro cell and ex vivo tumor tissue stainings. The peptide was further labeled with (18)F for positron emission tomography imaging studies. Cell uptake and efflux and ex vivo biodistribution were also done with (18)F-labeled osteosarcoma specific peptide. RESULTS:ASGALSPSRLDT was the dominant sequence isolated from biopanning and named as OSP-1. OSP-1 shares a significant homology with heparinase II/III family protein, which binds and reacts with heparan sulfate proteoglycans. The fluorescence staining showed that FITC-OSP-1-phage or Cy5.5-OSP-1 had high binding with a panel of osteosarcoma cell lines, much less binding with UM-SCC1 human head and neck squamous cell carcinoma cells, and almost no binding with 293T cells, whereas the scrambled peptide OSP-S had virtually no binding to all the cell lines. (18)F-OSP-1 had significantly higher accumulation in 143B tumor cells both in vitro and in vivo than (18)F-OSP-S. (18)F-OSP-1 also had higher uptake in 143B tumors than in UM-SCC-1 tumors. CONCLUSIONS:Our data suggest that OSP-1 peptide is osteosarcoma specific, and the binding site of OSP-1 might be related to heparan sulfate proteoglycans. Appropriately labeled OSP-1 peptide has the potential to serve as a novel probe for osteosarcoma imaging.

Project description:Coeliac disease (CD) is a common and complex disorder of the small intestine caused by intolerance to wheat gluten and related edible cereals like barley and rye. Peptides originating from incomplete gliadin digestion activate the lamina propria infiltrating T cells to release proinflammatory cytokines, which in turn cause profound tissue remodelling of the small intestinal wall. There is no cure for CD except refraining from consuming gluten-containing products.Phage from a random oligomer display library were enriched by repeated pannings against immobilised gliadin proteins. Phage from the final panning round were plated, individual plaques picked, incubated with host bacteria, amplified to a population size of 1011 to 1012 and purified. DNA was isolated from 1000 purified phage populations and the region covering the 36 bp oligonucleotide insert from which the displayed peptides were translated, was sequenced. Altogether more than 150 different peptide-encoding sequences were identified, many of which were repeatedly isolated under various experimental conditions. Amplified phage populations, each expressing a single peptide, were tested first in pools and then one by one for their ability to inhibit binding of human anti-gliadin antibodies in ELISA assays. These experiments showed that several of the different peptide-expressing phage tested inhibited the interaction between gliadin and anti-gliadin antibodies. Finally, four different peptide-encoding sequences were selected for further analysis, and the corresponding 12-mer peptides were synthesised in vitro. By ELISA assays it was demonstrated that several of the peptides inhibited the interaction between gliadin molecules and serum anti-gliadin antibodies. Moreover, ELISA competition experiments as well as dot-blot and western blot revealed that the different peptides interacted with different molecular sites of gliadin.We believe that several of the isolated and characterised gliadin-binding peptides described here could provide valuable tools for researchers in the field of CD by facilitating studies on localisation and uptake of various gliadin peptides in the small intestine. In future work, the potential of these peptides to detoxify gluten will be investigated.

Dataset Information

PDL1Binder: Identifying programmed cell death ligand 1 binding peptides by incorporating next-generation phage display data and different peptide descriptors.

Publications

PDL1Binder: Identifying programmed cell death ligand 1 binding peptides by incorporating next-generation phage display data and different peptide descriptors.

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