A story of peptides, lipophilicity and chromatography – back and forth in time

Erckes, Vanessa

doi:10.1039/d2md00027j

Cited by 10 publications

(9 citation statements)

References 115 publications

(235 reference statements)

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“…Lipophilicity is one of the important physicochemical descriptors and is related to both pharmacodynamic and pharmacokinetic properties. It determines the absorption, metabolism, distribution, excretion and toxicity of drugs (ADMET) [ 1 , 2 , 3 , 4 ]. It plays a significant role in the transport of molecules across membranes.…”

Section: Introductionmentioning

confidence: 99%

Study of Lipophilicity and ADME Properties of 1,9-Diazaphenothiazines with Anticancer Action

Morak‐Młodawska

Jeleń

Martula

et al. 2023

IJMS

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Lipophilicity is one of the key properties of a potential drug that determines the solubility, the ability to penetrate through cell barriers, and transport to the molecular target. It affects pharmacokinetic processes such as adsorption, distribution, metabolism, excretion (ADME). The 10-substituted 1,9-diazaphenothiazines show promising if not impressive in vitro anticancer potential, which is associated with the activation of the mitochondrial apoptosis pathway connected with to induction BAX, forming a channel in MOMP and releasing cytochrome c for the activation of caspases 9 and 3. In this publication, the lipophilicity of previously obtained 1,9-diazaphenothiazines was determined theoretically using various computer programs and experimentally using reverse-phase thin-layer chromatography (RP-TLC) and a standard curve. The study presents other physicochemical, pharmacokinetic, and toxicological properties affecting the bioavailability of the test compounds. ADME analysis was determined in silico using the SwissADME server. Molecular targets studies were identified in silico using the SwissTargetPrediction server. Lipinski’s rule of five, Ghose’s, and Veber’s rules were checked for the tested compounds, confirming their bioavailability.

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Section: Introductionmentioning

confidence: 99%

Study of Lipophilicity and ADME Properties of 1,9-Diazaphenothiazines with Anticancer Action

Morak‐Młodawska

Jeleń

Martula

et al. 2023

IJMS

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“…Generally, the peptide elution from RPC depends on the sequence, ion-pairing agent, organic solvent in the mobile phase, and alkyl chain of the stationary phase [ 10 ]. Increasing the hydrophobic nature and concentration of the ion-pairing agents enhances the retention time and peak resolution of the peptides due to an overall increase in hydrophobicity of the peptide and ion-pairing agent complexes.…”

Section: Discussionmentioning

confidence: 99%

Purification and Characterization of Novel Anti-MRSA Peptides Produced by Brevibacillus sp. SPR-20

et al. 2022

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Methicillin-resistant Staphylococcus aureus (MRSA) is listed as a high-priority pathogen because its infection is associated with a high mortality rate. It is urgent to search for new agents to treat such an infection. Our previous study isolated a soil bacterium (Brevibacillus sp. SPR-20), showing the highest antimicrobial activity against S. aureus TISTR 517 and MRSA strains. The present study aimed to purify and characterize anti-MRSA substances produced by SPR-20. The result showed that five active substances (P1–P5) were found, and they were identified by LC-MS/MS that provided the peptide sequences of 14–15 residues. Circular dichroism showed that all peptides contained β-strand and disordered conformations as the major secondary structures. Only P1–P4 adopted more α-helix conformations when incubated with 50 mM SDS. These anti-MRSA peptides could inhibit S. aureus and MRSA in concentrations of 2–32 μg/mL. P1 (NH2-VVVNVLVKVLPPPVV-COOH) had the highest activity and was identified as a novel antimicrobial peptide (AMP). The stability study revealed that P1 was stable in response to temperature, proteolytic enzymes, surfactant, and pH. The electron micrograph showed that P1 induced bacterial membrane damage when treated at 1× MIC in the first hour of incubation. The killing kinetics of P1 was dependent on concentration and time. Mechanisms of P1 on tested pathogens involved membrane permeability, leakage of genetic material, and cell lysis. The P1 peptide at a concentration up to 32 μg/mL showed hemolysis of less than 10%, supporting its safety for human erythrocytes. This study provides promising anti-MRSA peptides that might be developed for effective antibiotics in the post-antibiotic era.

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“…Molecular Weight (MW): The molecular weight of each peptide was calculated and compared to the established range (500-5000 Da) characteristic of drug-like peptides 25 . This parameter significantly influences a peptide's solubility, membrane permeability, and potential for toxicity.…”

Section: Physicochemical Propertiesmentioning

confidence: 99%

A Hybrid Diffusion Model for Stable, Affinity-Driven, Receptor-Aware Peptide Generation

Vishva Saravanan,

Choudhuri,

Ghosh

2024

Preprint

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The convergence of biotechnology and artificial intelligence has the potential to transform drug development, especially in the field of therapeutic peptide design. Peptides are short chains of amino acids with diverse therapeutic applications that offer several advantages over small molecular drugs, such as targeted therapy and minimal side effects. However, limited oral bioavailability and enzymatic degradation have limited their effectiveness. With advances in deep learning techniques, innovative approaches to peptide design have become possible. In this work, we demonstrate HYDRA: a hybrid deep learning approach that leverages the distribution modeling capabilities of a diffusion model and combines it with a binding affinity maximization algorithm that can be used forde novodesign of peptide binders given target receptors. As an application, we have used our approach to design therapeutic peptides targeting proteins expressed by Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) genes. The ability of our model to generate peptides conditioned on the target receptor’s binding sites makes it a promising approach for developing effective therapies for malaria and other diseases.

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A story of peptides, lipophilicity and chromatography – back and forth in time

Abstract: Peptides, as a part of the beyond the rule of 5 (bRo5) chemical space represent a unique class of pharmaceutical compounds. Because of their exceptional position in the chemical space...

Cited by 10 publications

References 115 publications

Study of Lipophilicity and ADME Properties of 1,9-Diazaphenothiazines with Anticancer Action

Study of Lipophilicity and ADME Properties of 1,9-Diazaphenothiazines with Anticancer Action

Purification and Characterization of Novel Anti-MRSA Peptides Produced by Brevibacillus sp. SPR-20

A Hybrid Diffusion Model for Stable, Affinity-Driven, Receptor-Aware Peptide Generation

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