ArticleInternational journal of molecular sciences2021
Virtual Evolution of HVEM Segment for Checkpoint Inhibitor Discovery.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 8 citations in OpenAlex.
- Insights into therapeutic peptides in the cancer-immunity cycle: Update and challenges.Acta pharmaceutica Sinica. B · 2024Review
- Rationally Designed Novel Antimicrobial Peptides Targeting Chitin Synthase for Combating Soybean Phytophthora Blight.International journal of molecular sciences · 2024Article
- A New Advanced Approach: Design and Screening of Affinity Peptide Ligands Using Computer Simulation Techniques.Current topics in medicinal chemistry · 2024Review
- Special Issue: Structure, Function and Evolution of Protein Domains.International journal of molecular sciences · 2022Article
- Identification of Immune-Related Genes Associated With Bladder Cancer Based on Immunological Characteristics and Their Correlation With the Prognosis.Frontiers in genetics · 2021Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Immune therapy has emerged as an effective treatment against cancers. Inspired by the PD-1/PD-L1 antibodies, which have achieved great success in clinical, other immune checkpoint proteins have drawn increasing attention in cancer research. B and T lymphocyte attenuator (BTLA) and herpes virus entry mediator (HVEM) are potential targets for drug development. The co-crystal structure of BTLA/HVEM have revealed that HVEM (26-38) fragment is the core sequence which directly involved on the interface. Herein, we conducted virtual evolution with this sequence by using saturation mutagenesis in silico and mutants with lower binding energy were selected. Wet-lab experiments confirmed that several of them possessed higher affinity with BTLA. Based on the best mutant of the core sequence, extended peptides with better efficacy were obtained. Furthermore, the mechanism of the effects of mutations was revealed by computational analysis. The mutated peptide discovered here can be a potent inhibitor to block BTLA/HVEM interaction and its mechanism may extend people's view on inhibitor discovery for the checkpoint pair.
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Registered trials
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