Structural Framework for the Modulation of the Activity of the Hybrid Antibiotic Peptide Cecropin A-Melittin [CA(1-7)M(2-9)] by Nε-Lysine Trimethylation

ChemBioChem ◽  
2011 ◽  
Vol 12 (14) ◽  
pp. 2177-2183 ◽  
Author(s):  
M. Dolores Díaz ◽  
Beatriz G. de la Torre ◽  
María Fernández-Reyes ◽  
Luis Rivas ◽  
David Andreu ◽  
...  
Keyword(s):  
Structural Framework ◽  
Cecropin A ◽  
Hybrid Antibiotic ◽  
Antibiotic Peptide

Designing Hybrid Antibiotic Peptide Conjugates To Cross Bacterial Membranes

2017 ◽  
Vol 28 (3) ◽  
pp. 793-804 ◽  
Author(s):  
Stephanie Deshayes ◽  
Wujing Xian ◽  
Nathan W. Schmidt ◽  
Shadi Kordbacheh ◽  
Juelline Lieng ◽  
...  
Keyword(s):  
Peptide Conjugates ◽  
Bacterial Membranes ◽  
Hybrid Antibiotic ◽  
Antibiotic Peptide

Design, Synthesis and Anticancer Activity of Site Specific Short Chain Cationic Peptide

2020 ◽  
Vol 17 (5) ◽  
pp. 631-646
Author(s):  
Ravi D. Sharma ◽  
Jainendra Jain ◽  
Ratan L. Khosa
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Cyclic Peptide ◽  
Cyclic Compound ◽  
Chemotherapeutic Agents ◽  
Short Chain ◽  
Rational Approach ◽  
Phase Method ◽  
Host Defense Peptides ◽  
Cecropin A

Background: In spite of current progress in treatment methods, cancer is a major source of morbidity and death rate all over the world. Traditional chemotherapeutic agents aim to divide cancerous cells, are often associated with deleterious side effects to healthy cells and tissues. Host defense peptides Cecropin A and B obtained from insects are capable to lyses various types of human cancer cells at peptide concentrations which are not fatal to normal eukaryotic cells. Methods: In the present work we have designed short chain α-helical linear and cyclic peptide from cecropin A having same cationic charge, hydrophobicity and helicity. Synthesis of designed novel short chain linear (10) and cyclic compound (12) was accomplished by using solution phase method. All the coupling reactions were carried out by using dicyclohexylcarbodiimide (DCC) as the coupling reagent at room temperature in the presence of N-methylmorpholine (NMM) as the base. The Structure of newly synthesized peptidse were elucidated by 1H-NMR, 13C-NMR, FT-IR, FABMS and elemental analysis data.Cytotoxicity of synthesized compound was tested against Dalton’s Lymphoma Ascites (DLA), Ehrlich’s Ascites Carcinoma (EAC) and MCF-7 cell lines by using MTT assay and 5-FU as reference compound. Results: From biological assessment,it was found that short chain cyclicpeptide12 showed high level of cytotoxic activity against DLA and EAC cell lines. Conclusion: By utilizing a structure-based rational approach to anticancer peptide design from cecropin A, we were able to develop short chain linear and cyclic peptides having same charge, hydrophobicity and with improved activity. Systematically removing amino acids, we were able to retaining peptide charge and hydrophobicity/hydrophilicity in linear and cyclic peptide which results to optimize the anticancer activity against DLA and EAC cell lines.

scholarly journals Metabolic Reprogramming of Fibroblasts as Therapeutic Target in Rheumatoid Arthritis and Cancer: Deciphering Key Mechanisms Using Computational Systems Biology Approaches

Cancers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 35
Author(s):  
Sahar Aghakhani ◽  
Naouel Zerrouk ◽  
Anna Niarakis
Keyword(s):  
Rheumatoid Arthritis ◽  
Extracellular Matrix ◽  
Systems Biology ◽  
Healing Process ◽  
Metabolic Reprogramming ◽  
Critical Event ◽  
Wound Healing Process ◽  
Computational Systems Biology ◽  
Structural Framework ◽  
Computational Systems

Fibroblasts, the most abundant cells in the connective tissue, are key modulators of the extracellular matrix (ECM) composition. These spindle-shaped cells are capable of synthesizing various extracellular matrix proteins and collagen. They also provide the structural framework (stroma) for tissues and play a pivotal role in the wound healing process. While they are maintainers of the ECM turnover and regulate several physiological processes, they can also undergo transformations responding to certain stimuli and display aggressive phenotypes that contribute to disease pathophysiology. In this review, we focus on the metabolic pathways of glucose and highlight metabolic reprogramming as a critical event that contributes to the transition of fibroblasts from quiescent to activated and aggressive cells. We also cover the emerging evidence that allows us to draw parallels between fibroblasts in autoimmune disorders and more specifically in rheumatoid arthritis and cancer. We link the metabolic changes of fibroblasts to the toxic environment created by the disease condition and discuss how targeting of metabolic reprogramming could be employed in the treatment of such diseases. Lastly, we discuss Systems Biology approaches, and more specifically, computational modeling, as a means to elucidate pathogenetic mechanisms and accelerate the identification of novel therapeutic targets.

Exploring Galleria mellonella larval model to evaluate antibacterial efficacy of Cecropin A (1-7)- Melittin against multi-drug resistant enteroaggregative Escherichia coli

2021 ◽  
Author(s):  
Jess Vergis ◽  
S V S Malik ◽  
Richa Pathak ◽  
Manesh Kumar ◽  
Nitin V Kurkure ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Galleria Mellonella ◽  
In Vivo Model ◽  
Drug Resistant ◽  
Physiological Concentration ◽  
Microbial Drug Resistance ◽  
Cecropin A ◽  
Screening And Identification

Abstract High throughput in vivo laboratory models is need for screening and identification of effective therapeutic agents to overcome microbial drug-resistance. This study was undertaken to evaluate in vivo antimicrobial efficacy of short-chain antimicrobial peptide- Cecropin A (1–7)-Melittin (CAMA) against three multi- drug resistant enteroaggregative Escherichia coli (MDR-EAEC) field isolates in a Galleria mellonella larval model. The minimum inhibitory concentration (MIC; 2.0 mg/L) and minimum bactericidal concentration (MBC; 4.0 mg/L) of CAMA were determined by microdilution assay. CAMA was found to be stable at high temperatures, physiological concentration of cationic salts and proteases; safe with sheep erythrocytes, secondary cell lines and commensal lactobacilli at lower MICs; and exhibited membrane permeabilisation. In vitro time-kill assay revealed concentration- and time-dependent clearance of MDR-EAEC in CAMA-treated groups at 30 min. CAMA- treated G. mellonella larvae exhibited an increased survival rate, reduced MDR-EAEC counts, immunomodulatory effect and proved non-toxic which concurred with histopathological findings. CAMA exhibited either an equal or better efficacy than the tested antibiotic control, meropenem. This study highlights the possibility of G. mellonella larvae as an excellent in vivo model for investigating the host-pathogen interaction, including the efficacy of antimicrobials against MDR-EAEC strains.

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