Rational design of an anti-cancer peptide inhibiting CD147 / Cyp A interaction

Maani, Zahra; Farajnia, Safar; Rahbarnia, Leila; Hosseingholi, Elaheh Zadeh; Khajehnasiri, Nazli; Mansouri, Parisa

doi:10.1016/j.molstruc.2022.134160

Cited by 7 publications

(4 citation statements)

References 40 publications

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“…Moreover, we validated the performance of PALM by ClusPro 40,41 and SnugDock 13 , which are widely accepted antibody validation tools [56][57][58][59] . PALM was able to generate antibody CDRH3 sequences targeting the stable peptide in the HR2 region of SARS-CoV-2.…”

Section: Discussionmentioning

confidence: 99%

De novogeneration of antibody CDRH3 with a pre-trained generative large language model

He,

Guan

et al. 2023

Preprint

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Artificial Intelligence (AI) techniques have made great advances in assisting antibody design. However, antibody design still heavily relies on isolating antigen-specific antibodies from serum, which is a resource-intensive and time-consuming process. To address this issue, we propose a Pre-trained Antibody generative large Language Model (PALM) for the de novo generation of artificial antibodies heavy chain complementarity-determining region 3 (CDRH3) with desired antigen-binding specificity, reducing the reliance on natural antibodies. We also build a high-precision model antigen-antibody binder (A2binder) that pairs antigen epitope sequences with antibody sequences to predict binding specificity and affinity. PALM-generated antibodies exhibit binding ability to SARS-CoV-2 antigens, including the emerging XBB variant, as confirmed through in-silico analysis and in-vitro assays. The in-vitro assays validated that PALM-generated antibodies achieve high binding affinity and potent neutralization capability against both wild-type and XBB spike proteins of SARS-CoV-2. Meanwhile, A2binder demonstrated exceptional predictive performance on binding specificity for various epitopes and variants. Furthermore, by incorporating the attention mechanism into the PALM model, we have improved its interpretability, providing crucial insights into the fundamental principles of antibody design.

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Section: Discussionmentioning

confidence: 99%

De novogeneration of antibody CDRH3 with a pre-trained generative large language model

He,

Guan

et al. 2023

Preprint

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“…The CypA/ CD147 interaction is a crucial route in some cancer types and is also necessary for the COVID-19 virus to infect the host cell. Thus, it is suggested that the designed peptide may prove to be an appealing treatment target for controlling different tumor types as well as COVID-19 infection (Maani et al, 2023). Melittin showed selective cytotoxicity against HER2-enriched breast cancer cell lines (MDA-MB-453 and SKBR3) and Triple Negative Breast Cancer (TNBC) cell lines (SUM 159 and SUM149), while exhibiting minimal cytotoxicity against normal cell lines (HDFa, and MCF 10A and MCF-12A cells) (Duffy et al, 2020).…”

Section: Bee Venommentioning

confidence: 99%

Revisiting edible insects as sources of therapeutics and drug delivery systems for cancer therapy

Sinha,

Choudhury

2024

Front. Pharmacol.

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Cancer has been medicine’s most formidable foe for long, and the rising incidence of the disease globally has made effective cancer therapy a significant challenge. Drug discovery is targeted at identifying efficacious compounds with minimal side effects and developments in nanotechnology and immunotherapy have shown promise in the fight against this complicated illness. Since ancient times, insects and insect-derived products have played a significant role in traditional medicine across several communities worldwide. The aim of this study was to inspect the traditional use of edible insects in various cultures and to explore their modern use in cancer therapy. Edible insects are sources of nutrients and a variety of beneficial substances with anticancer and immunomodulatory potential. Recently, insect derived bioactive-components have also been used as nanoparticles either in combination with chemotherapeutics or as a nano-cargo for the enhanced delivery of chemotherapeutic drugs due to their high biocompatibility, low bio-toxicity, and their antioxidant and anticancer effects. The crude extracts of different edible insects and their active components such as sericin, cecropin, solenopsin, melittin, antimicrobial peptides and fibroin produce anti-cancer and immunomodulatory effects by various mechanisms which have been discussed in this review.

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“…Moreover, MLT blocked the MMP pathway and inhibited caspase activity by intervening in the interaction between CD147 and its ligand cyclophilin A (CypA). The latest research reported that the C-terminal portion of MLT was fused to a TAT cell-penetrating peptide by the GGGS linker to construct the TM peptide, which could be bound to CD147 with sufficient binding energy to block the cyclophilin A/CD147 interaction [ 118 ] (Fig. 7 ).…”

Section: Targeted Delivery Strategies Of Mlt For Tumor Therapymentioning

confidence: 99%

“…C Coarse-grained simulation of the TM peptide interaction with the DOPC/DOPS model membrane after 1500 ns (yellow = water, red = protein, blue, pink, light gray = lipid). Reproduced with permission from [118]. Copyright 2023, Elsevier synergistic cytotoxicity as well as a better effect on controlling tumor growth than monotherapy [120].…”

Section: Aptamer-based Conjugationmentioning

confidence: 99%

Recent advances in melittin-based nanoparticles for antitumor treatment: from mechanisms to targeted delivery strategies

Yu,

Jia,

et al. 2023

J Nanobiotechnol

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As a naturally occurring cytolytic peptide, melittin (MLT) not only exhibits a potent direct tumor cell-killing effect but also possesses various immunomodulatory functions. MLT shows minimal chances for developing resistance and has been recognized as a promising broad-spectrum antitumor drug because of this unique dual mechanism of action. However, MLT still displays obvious toxic side effects during treatment, such as nonspecific cytolytic activity, hemolytic toxicity, coagulation disorders, and allergic reactions, seriously hampering its broad clinical applications. With thorough research on antitumor mechanisms and the rapid development of nanotechnology, significant effort has been devoted to shielding against toxicity and achieving tumor-directed drug delivery to improve the therapeutic efficacy of MLT. Herein, we mainly summarize the potential antitumor mechanisms of MLT and recent progress in the targeted delivery strategies for tumor therapy, such as passive targeting, active targeting and stimulus-responsive targeting. Additionally, we also highlight the prospects and challenges of realizing the full potential of MLT in the field of tumor therapy. By exploring the antitumor molecular mechanisms and delivery strategies of MLT, this comprehensive review may inspire new ideas for tumor multimechanism synergistic therapy.

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Rational design of an anti-cancer peptide inhibiting CD147 / Cyp A interaction

Cited by 7 publications

References 40 publications

De novogeneration of antibody CDRH3 with a pre-trained generative large language model

De novogeneration of antibody CDRH3 with a pre-trained generative large language model

Revisiting edible insects as sources of therapeutics and drug delivery systems for cancer therapy

Recent advances in melittin-based nanoparticles for antitumor treatment: from mechanisms to targeted delivery strategies

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