Novel Peptide–Drug Conjugates with Dual Anticancer Activity DOI Open Access
Siobhán O’Flaherty, Olga A. Luzina, Nadezhda S. Dyrkheeva

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 12411 - 12411

Published: Nov. 19, 2024

Cationic antimicrobial peptides (AMPs), also called host defence peptides, have established and anticancer activities. Conjugation of an AMP to a bioactive molecule with complementary activity can address some the clinical limitations peptide candidate. This approach has been particularly applied in applications AMPs, but it remains relatively less explored generation candidates. In this study, two usnic acid derivatives, based on hydrazinothiazole benzylidenefuranone pharmacophore moieties, respectively, were conjugated L-K6, lysine/leucine-rich AMP, through new pyrazole ligation intrinsically driven by cargo molecule. Both components, derivative peptide, are selectively active against cancer cells, targeting human DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (TDP1) damage, respectively. The conjugates, hydrazone linkage, exhibited pleiotropic effects, ranging from reduction parent drugs their conservation or even enhancement. Notably, conjugates retained anti-TDP1 displayed intermediate, higher, cytotoxicities glioblastoma compared individual components.

Language: Английский

In silico, in vitro and in vivo toxicity assessment of the antitumoral peptide GK-1 DOI Creative Commons
Sergio Sifontes, Juan Alberto Hernández-Aceves, Carmen Garrido

et al.

Toxicology Reports, Journal Year: 2025, Volume and Issue: 14, P. 101962 - 101962

Published: Feb. 12, 2025

Peptide drugs have emerged as an attractive alternative for cancer treatment due to their potency, high specificity, general safety and low cost. GK-1 is a linear 18 amino acid peptide with proven immunomodulator, antitumor antimetastatic capacity in animal models. Preclinical toxicity studies its use vaccine adjuvant demonstrated various assay systems, but comprehensive exploration of profile required be used immunotherapy. Therefore, the present work, potential was predicted ToxinPred 3.0 software, vitro cytotoxicity, single-dose repeated-dose by subcutaneous route mice were experimentally assessed. non-toxic did not exhibit cytotoxicity several non-tumor tumor cell lines primary cultures at concentrations up 500 µM, reinforcing previous pointing that antitumoral effect mediated cytotoxicity. The study evidence local or systemic maximum tested dose 1000 mg/kg. Moreover, no toxic effects observed based on four doses administered weekly 300 Considering effective triple-negative breast melanoma models 5 mg/kg, results support candidate.

Language: Английский

Citations

1
The potential applications of peptide-loading complex in cancer treatment DOI Creative Commons

Zhidu Song,

Ying Tao, Jiaxin You

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 3, 2025

Immunotherapy for cancer has made significant strides in the last several years. The prognosis patients significantly improved as a result, particularly hematological diseases. However, it was discovered that translating these achievements to solid tumors proved challenging. peptide-loading complex (PLC), temporary multisubunit membrane assembly endoplasmic reticulum (ER), is crucial initiating hierarchical immune response. Chaperones calreticulin and tapasin make up PLC, unique class I glycoproteins, thiooxido-reductase ERp57, transporter associated with antigen processing. loading editing of major histocompatibility (MHC-I) molecules peptide translocation into ER are synchronized by PLC. One escape strategies revealed so far changes expression MHC molecules. This because antigens presenting T-lymphocytes controlling NK cell activity. Furthermore, decreased MHC-I been linked malignancies resistant T-cell-based immunotherapies (adoptive transfer antitumor CD8 T-cells or checkpoint inhibition). PLC essential T-cell priming, differentiation, tumor growth control can bind wide range allomorphs. In this review, we have looked PLC’s function effects all forms improve therapy techniques.

Language: Английский

Citations

1
Efficient Synthesis, Stability-Guided Optimization and Anticancer Evaluation of Bee Venom Peptide Melittin DOI
Qing Liu,

Shi‐Xi Jia,

Qiao-Na Chi

et al.

Published: Jan. 1, 2025

Natural cytotoxic peptides (NCPs) are emerging sources of novel anticancer chemotherapeutics. Especially, Melittin, which is the major component bee venom and first-in-class NCP, has been considered as a promising scaffold. Nevertheless, classical linear, cationic, amphipathic, membrane-lytic peptide, Melittin may be easily degraded by proteases, suffering from poor stability, moderate durability, severe hemolysis. In this study, applying terminal modification hybridization strategies, ten Melittin-based derivatives were designed, synthesized, investigated for their potential. The robust economic synthetic method, in vitro efficiency, time-kill kinetics, serum anti-migration activity, hemolysis effects, mechanism explored. As expected, exhibited highly potent cytotoxicity against all six tested cancer cell lines. particular, compared with natural derived LJ-5 containing both N-terminal acetylation C-terminal hydrazidation, LJ-6, methotrexate MTX-GFLG-Melittin conjugate significantly improved proteolytic more durable higher well reduced effects. Besides, it was further verified that LJ-6 could efficiently disrupt integrity membrane, localize to mitochondria rapidly reduce mitochondrial membrane potential cells. Collectively, method stability-guided optimization conducted on affording hydrolysis-resistant serve candidates useful references optimizations peptides.

Language: Английский

Citations

0
Peptide-driven strategies against lung cancer DOI

Vijayshree S Karankar,

Saurabh Awasthi, Nidhi Srivastava

et al.

Life Sciences, Journal Year: 2025, Volume and Issue: unknown, P. 123453 - 123453

Published: Feb. 1, 2025

Language: Английский

Citations

0
Efficient synthesis, stability-guided optimization and anticancer evaluation of bee venom peptide Melittin DOI
Qing Liu,

Shi‐Xi Jia,

Qiao-Na Chi

et al.

Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: 159, P. 108344 - 108344

Published: March 4, 2025

Language: Английский

Citations

0
Therapeutic Potential of Plant‐Derived Peptides for Preventing or Treating Hypertension and Diabetes DOI
Debojit Baidya Choudhury,

Tariq Abdullah Mir,

Khalid Gul

et al.

Journal of Food Process Engineering, Journal Year: 2025, Volume and Issue: 48(4)

Published: April 1, 2025

ABSTRACT Interest in plant‐derived bioactive peptides (BAPs) is increasing due to their potential therapeutic effects, low toxicity, abundance, scalability, and cost‐effectiveness. These can be obtained by hydrolyzing plant proteins from a diverse range of sources, including legumes, cereals, grains, oilseeds, tubers. This review discusses the benefits these on human health, addressing current challenges translating research into practical use. The structural aspects combating hypertension diabetes, encompassing structure–activity relationship studies, vitro vivo methodologies, absorption pathways are also discussed. Additionally, it explores molecular features, physicochemical properties, gastrointestinal fate, biological activities various peptides, reducing blood pressure sugar. hold promise as agents functional foods, supplements, pharmaceuticals, pending rigorous clinical trials ascertain efficacy safety. Successful could position innovative antihypertensive antidiabetic agents.

Language: Английский

Citations

0
Key considerations based on pharmacokinetic/pharmacodynamic in the design of antibody-drug conjugates DOI Creative Commons
Yangyang Gao, Yuwei Xia, Yixin Chen

et al.

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 14

Published: Jan. 9, 2025

Antibody-drug conjugate (ADC) is an anticancer drug that links toxins to specifically targeted antibodies via linkers, offering the advantages of high target specificity and cytotoxicity. However, complexity its structural composition poses a greater difficulty for design studies. Pharmacokinetic/pharmacodynamic (PK/PD) based consideration ADCs has increasingly become hot research topic optimal in recent years, providing possible ideas obtaining with desirable properties. From assessment ADC action process on PK/PD, we introduce main strategies ADCs. In addition, investigated solve prominent problems clinic summarized evaluated specific ways optimize various PK/PD model from two perspectives optimizing structure properties drugs themselves. Through selection antigen, optimization linker, novel small molecule as payload, ADC, overcoming multi-drug resistance improving tumor penetration surface modification bystander effect provide more comprehensive accurate framework designing new We've expounded comprehensively applying pharmacokinetics or pharmacodynamics while obtain higher efficacy fewer side effects. ADC's property coming into play vivo study strategy, methods recommendations it been study-approved exert subtle role development whether preclinical trials clinical promotion. The unfolds detailed mechanism action, making easier control related parameters limited inevitable off-target toxicity remain challenging bottleneck.

Language: Английский

Citations

0
Sweet MOFs: Exploring the Potential and Restraints of Integrating Carbohydrates with Metal-Organic Frameworks for Biomedical Applications DOI Creative Commons
Alessio Zuliani, Víctor Ramos, Alberto Escudero

et al.

Nanoscale Horizons, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Metal–organic frameworks (MOFs) functionalized with carbohydrates offer promising biocompatible systems for biomedical applications. This review discusses recent progress and challenges in using these innovative “sweet” composites.

Language: Английский

Citations

2
Radiosynthesis, Preparation, and Biological Evaluation of [99MTC]Tricarbonyl Pantoprazole for Stomach Ulcer Detection in Mice DOI
M. H. Sanad, H. M. Eyssa,

F. A. Marzook

et al.

Pharmaceutical Chemistry Journal, Journal Year: 2024, Volume and Issue: 58(6), P. 950 - 956

Published: Sept. 1, 2024

Language: Английский

Citations

1
Stapled Peptides: An Innovative and Ultimate Future Drug Offering a Highly Powerful and Potent Therapeutic Alternative DOI Creative Commons
Do‐Hee Kim, Sung‐Min Kang

Biomimetics, Journal Year: 2024, Volume and Issue: 9(9), P. 537 - 537

Published: Sept. 5, 2024

Peptide-based therapeutics have traditionally faced challenges, including instability in the bloodstream and limited cell membrane permeability. However, recent advancements α-helix stapled peptide modification techniques rekindled interest their efficacy. Notably, these developments ensure a highly effective method for improving stability enhancing penetration. Particularly realm of antimicrobial peptides (AMPs), application has significantly increased been successfully applied to many peptides. Furthermore, constraining secondary structure also proven enhance biological activity. In this review, entire process through which hydrocarbon-stapled attain improved drug-like properties is examined. First, essential structural elements required activity as drugs are validated, specific residues identified using alanine scanning, stapling strategically incorporated at precise locations. Additionally, mechanisms by structure-based function AMPs explored, providing comprehensive engaging discussion.

Language: Английский

Citations

0