Peptides as pharmaceutical leads
a mechanistic based exploration through molecular modeling and docking studies
Journal name: World Journal of Pharmaceutical Research
Original article title: Peptides as pharmaceutical leads
The WJPR includes peer-reviewed publications such as scientific research papers, reports, review articles, company news, thesis reports and case studies in areas of Biology, Pharmaceutical industries and Chemical technology while incorporating ancient fields of knowledge such combining Ayurveda with scientific data.
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Subtitle: a mechanistic based exploration through molecular modeling and docking studies
Original source:
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Ruchi Omar, Sweta Sharma, Veejendra K. Yadav and Arpita Yadav
World Journal of Pharmaceutical Research:
(An ISO 9001:2015 Certified International Journal)
Full text available for: Peptides as pharmaceutical leads
Source type: An International Peer Reviewed Journal for Pharmaceutical and Medical and Scientific Research
Doi: 10.20959/wjpr20183-10882
Download the PDF file of the original publication
Summary of article contents:
Introduction
The emergence of antibiotic resistance poses significant challenges to global health, as demonstrated by increasing incidences of multidrug resistance in pathogens such as Mycobacterium tuberculosis. Despite the historical success of antibiotics in treating bacterial infections, the overuse of these drugs has accelerated the development of resistance. In this context, naturally occurring antimicrobial peptides (AMPs) are explored as potential pharmaceutical leads owing to their unique mechanisms of action. This study investigates the mechanistic aspects of AMPs, focusing on their antifungal and anti-HIV properties through molecular modeling and docking studies while also addressing their pharmacokinetic limitations.
Ion Carriage and Antimicrobial Activity
One of the intriguing attributes of AMPs is their ability to act as ionophores, facilitating the transport of metal ions across microbial cell membranes. This ion carriage capability can destabilize microbial cells by creating ionic gradients, potentially leading to cell lysis. The study uses Hartree-Fock (HF) molecular orbital calculations to analyze the interaction between AMPs and metal ions, demonstrating that the binding affinity of the peptides to ions is influenced by their charge and conformation. The capacity of AMPs to bind metal ions not only contributes to their antibacterial properties but also offers a possible avenue for therapeutic applications such as heavy metal detoxification.
Mechanistic Understanding of Anti-HIV Activity
In addition to their antimicrobial properties, AMPs exhibit promise in combating viral infections, particularly HIV. The study emphasizes that AMPs can inhibit the viral transcription process by interacting non-covalently with the RNA template of the HIV virus, thereby interrupting essential replication activities. By utilizing molecular docking techniques, the research illustrates how specific AMPs can effectively block the primer binding site (PBS) of the viral RNA, an interaction critical for the reverse transcription process. This mechanistic insight offers a foundation for designing peptide-based therapeutics aimed at suppressing HIV replication.
Design of Peptidomimetic Compounds
Given the challenges of bioavailability and pharmacokinetics that hinder the clinical application of natural AMPs, the study proposes the design of peptidomimetic compounds. By altering the peptide sequences and introducing artificial backbones through computational modeling, the authors aim to enhance the druggability features of these compounds. The optimization process, guided by ADME (absorption, distribution, metabolism, and excretion) property assessments, reveals opportunities for creating effective therapeutic agents with improved stability and efficacy in treating intertwined diseases like HIV and internal fungal infections.
Conclusion
This research presents a strategic exploration of the potential of antimicrobial peptides as pharmaceutical leads through a mechanistic understanding of their properties and interactions. By leveraging molecular modeling and docking studies, the authors have elucidated the ion transport and anti-HIV mechanisms of AMPs, subsequently guiding the design of peptidomimetic compounds that circumvent traditional pharmacokinetic limitations. The findings underscore the importance of computational tools in modern pharmaceutical research, paving the way for the development of novel, safe, and effective therapeutic agents in addressing critical health challenges, including microbial resistance and viral infections.
FAQ section (important questions/answers):
What is the focus of the study on antimicrobial peptides?
The study explores the pharmaceutical potential of naturally occurring antimicrobial peptides, focusing on their antifungal and anti-HIV properties through molecular modeling and docking studies.
Why are antimicrobial peptides considered over traditional antibiotics?
Antimicrobial peptides are considered due to their natural origin, reduced toxicity, and ability to address microbial resistance issues, which are significant challenges with traditional antibiotics.
What methodologies were used in the study to evaluate peptides?
The study employed quantum mechanical Hartree-Fock calculations, molecular modeling, and docking studies to analyze peptide interactions and design peptidomimetic compounds with better pharmacokinetic properties.
What challenges have antimicrobial peptides faced in drug development?
Despite their potential, antimicrobial peptides have struggled with poor pharmacokinetics and bioavailability, limiting their successful commercialization as medications.
How do the designed peptidomimetic compounds enhance druggability?
Peptidomimetic compounds are designed to reduce molecular weight and optimize ADME properties, which improves their absorption, distribution, metabolism, and excretion profiles for better druggability.
What is the significance of the designed compounds in medicine?
The designed compounds aim to provide safer, robust options for treating intertwined diseases like HIV and internal fungal infections, thus addressing significant health challenges.
Glossary definitions and references:
Scientific and Ayurvedic Glossary list for “Peptides as pharmaceutical leads”. This list explains important keywords that occur in this article and links it to the glossary for a better understanding of that concept in the context of Ayurveda and other topics.
1) Activity:
The term 'Activity' refers to the biological effectiveness of a compound, particularly antimicrobial peptides in this study. It emphasizes the ability of these compounds to inhibit the growth of harmful pathogens like bacteria and viruses, thus illustrating their potential therapeutic value in medicine.
2) Calculation:
In the context of the study, 'Calculation' refers to the quantitative processes used to evaluate interaction energies, binding affinities, and the pharmacokinetic properties of antimicrobial peptides. Such calculations, especially those involving quantum mechanics and molecular modeling, are crucial for understanding how these peptides function at a molecular level.
3) Table:
'Table' signifies the organized data representation, highlighting the characteristics and activities of various antimicrobial peptides. Tables elucidate critical information, such as minimum inhibitory concentrations (MICs) of peptides against different pathogens, thereby enabling easier comparison and analysis of their potential efficacy in therapeutic applications.
4) Drug:
'Drugs' encompasses a broader category that includes any bioactive substances intended for therapeutic use. The study focuses on designing new drugs derived from naturally occurring antimicrobial peptides, aiming to develop safer, more effective therapies for various diseases, especially against resistant pathogens.
5) Antibiotic (Antibacterial):
'Antibacterial' denotes properties of substances that act against bacteria. The study emphasizes the potential of certain antimicrobial peptides to exhibit antibacterial activities, serving as a promising alternative to conventional antibiotics in combating resistant bacterial strains.
6) Study (Studying):
The word 'Study' denotes the structured inquiry into the pharmaceutical potential of antimicrobial peptides through molecular modeling and docking studies. It signifies rigorous scientific exploration aimed at understanding the mechanistic attributes of these peptides and their implications for drug development against complex infectious diseases.
7) Pose:
'Pose' signifies the specific conformation or arrangement of a molecule in molecular docking studies. Analyzing poses of peptides bound to viral templates provides insight into the interactions critical for inhibiting viral replication, offering a pathway to designing more effective pharmaceutical compounds.
8) Disease:
'Diseases' is the plural form of 'disease' and refers to various pathological conditions affecting health. This study specifically targets diseases like HIV and fungal infections, highlighting the importance of designing effective therapeutic agents to combat these interrelated health crises.
9) Surface:
'Surface' refers to the accessible area of a molecule that interacts with solvents or biological targets. In pharmacokinetics, surface area impacts the absorption and interaction of peptides in the system, which is crucial in assessing their potential as drug candidates.
10) Species:
'Species' pertains to distinct groups of organisms with common characteristics. The research addresses various microbial species affected by antimicrobial peptides, underlining the need for effective treatment options across different pathogenic species plagued by antibiotic resistance.
11) India:
'India' refers to the geographical context of the study, indicating its origin and the setting for the research conducted by Indian scientists. It illustrates India's role in addressing global health concerns, particularly antimicrobial resistance and disease management.
12) Field:
The 'Field' describes the area of research dedicated to pharmaceutical sciences and antimicrobial therapy. It highlights the multidisciplinary nature of the studies involving chemistry, biology, and medicine, aiming to innovate and enhance drug development and effective treatments.
13) New Delhi:
'New Delhi' is the capital city of India, relevant as a hub for scientific research and funding, including the support from organizations based in the capital for various research projects, thereby facilitating advancements in pharmaceutical sciences.
14) Wild boar:
'Wild boar' refers to an animal species from which certain antimicrobial peptides are derived. The study mentions specific peptides derived from such species, demonstrating the natural sources of therapeutic agents and their biological significance in medical applications.
15) Toxicity:
'Toxicity' refers to the harmful effects of substances on biological systems. The study aims to evaluate the toxicity profiles of antimicrobial peptides, assessing their safety and efficacy to ensure they are suitable for therapeutic use in human patients.
16) Sharman (Sarma, Sarman, Sharma):
'Sharma' is a surname of one of the contributors to the study. It emphasizes the collaborative efforts of researchers in contributing to novel findings in the fields of chemistry and pharmaceutical sciences through their joint research endeavors.
17) Delhi:
'Delhi' not only refers to the capital city of India but also serves as a center for research and development in pharmaceuticals. This implies the contribution of institutions based in Delhi towards advancements in drug discovery and pharmaceutical research.
18) Ruci:
'Ruchi' is the first name of one of the authors of the study. Recognizing individual contributors highlights the collaborative nature of scientific research and the importance of diverse researchers in achieving significant breakthroughs in understanding antimicrobial peptides.
19) Boar:
'Boar' represents a species that is relevant in the context of the study for its contribution to the discovery of bioactive peptides. Its mention underscores the significance of utilizing animal-derived peptides in addressing the need for effective antimicrobial properties in pharmaceuticals.
20) Post:
'Post' suggests the subsequent actions or outcomes following the study. It denotes the next steps in research or potential applications of the findings to further enhance drug efficacy and combat challenges in treating resistant infections.
21) Viru:
'Viru' signals a connection to viruses, specifically their replication processes. This reflects the study's emphasis on exploring antimicrobial peptides as potential inhibitors of viral activities, particularly in the context of HIV, thereby addressing critical health issues.
22) Pur:
'Poor' typically describes inadequate conditions. In this context, it relates to the prevailing challenges with existing pharmaceuticals, including poor pharmacokinetics of peptide-based drugs, stressing the need for improved formulations to achieve therapeutic effectiveness.
23) Spider poison (Spider venom):
'Spider venom' denotes a natural source of bioactive compounds, wherein certain peptides exhibit therapeutic properties. The study connects this intriguing source to exploring novel treatments for various health conditions, enriching the search for natural pharmaceuticals.
24) Human body:
'Human body' indicates the system where drugs are administered and their effects are observed. The research focuses on the interaction of antimicrobial peptides within the human body to ascertain their therapeutic potentials and evaluate safety for clinical use.
25) Pharmacological:
'Pharmacological' pertains to the study of drug actions and interactions. This highlights the study's focus on evaluating the pharmacological profiles of antimicrobial peptides to understand their therapeutic mechanisms and enhance drug development strategies.
26) Tuberculosis:
'Tuberculosis' is a serious infectious disease that affects human health. The focus on this disease in the study emphasizes the need for innovative treatments to combat its spread, as drug resistance is a significant challenge in its management.
27) Perception:
'Perception' indicates the understanding or viewpoint regarding the therapeutic effectiveness of antimicrobial peptides. It emphasizes the study's goal of reshaping perceptions about traditional drug efficacy and exploring novel approaches to combat resistance.
28) Discussion:
'Discussion' represents the analytical portion of the study where findings are interpreted and implications are drawn. It is crucial for understanding the significance of the research outcomes in the broader context of pharmaceutical development.
29) Developing:
'Developing' refers to the process of creating new therapies or enhancing existing ones. This word reflects the core intention of the study, which is to innovate and formulate better pharmaceutical agents from antimicrobial peptides for effective disease intervention.
30) Science (Scientific):
'Science' encompasses the systematic study of the natural world. In this study, it highlights the interdisciplinary approach combining chemistry, biology, and pharmacology to explore new therapeutic modalities.
31) Medicine:
'Medicine' pertains to the field focused on the treatment and prevention of diseases. This study represents an effort to contribute to medicinal science through research aimed at isolating and optimizing therapeutic peptides for clinical use.
32) Mutation:
'Mutation' refers to the changes made in peptide sequences or structures during the study. This highlights the experimental strategies undertaken to improve the functional properties of antimicrobial peptides for enhanced therapeutic effectiveness.
33) Relative:
'Relative' refers to the relationship between different pharmaceutical characteristics, such as potency and safety profiles. This understanding is crucial in evaluating the effectiveness of antimicrobial peptides against traditional drugs.
34) Company:
'Company' signifies the pharmaceutical industries involved in drug development. The implications of this study aim to benefit companies by providing novel lead compounds that can be developed into safe and effective medications.
35) Insect:
'Insect' also represents a source of naturally occurring antimicrobial peptides highlighted in the study. The focus on insect-derived peptides underlines their promise in innovative drug development.
36) Nature:
'Nature' refers to the environment from which biological compounds, including antimicrobial peptides, are sourced. The study advocates for utilizing natural products in drug development to discover effective therapies.
37) Reason:
'Reason' denotes the justification for undertaking the research, emphasizing the dire need for effective treatments against microbial resistance and diseases challenging global health.
38) Spider:
'Spider' emphasizes the relevance of certain arachnids in producing unique venoms. Spider-derived peptides may offer therapeutic properties, showcasing the potential of exploring such natural products in pharmaceuticals.
39) Indian:
'Indian' reflects the geographical context of the research, underlining the contributions by researchers in that region and highlighting local biodiversity's role in biopharmaceutical innovation.
40) Kumar:
'Kumar' is the surname of one of the researchers involved in the study. Acknowledging contributors underscores the collaborative efforts of scientists striving to advance the understanding and application of antimicrobial peptides.
41) Death:
'Death' relates to the severe outcomes of untreated infections and diseases. The study stresses the urgency of developing effective antimicrobial agents to prevent fatalities arising from resistant pathogens.
42) Money:
'Money' denotes the financial aspects related to pharmaceutical research and development. It underscores the importance of cost-effective solutions in drug development to ensure the sustainability of therapeutic innovations.
43) Shasha (Sasa, Shasa, Sasha):
'Sasa' likely refers to a specific context within the study, potentially a specific parameter or characteristic linked to the research focus, reflecting the intricate nature of peptide interactions within biological systems.
44) Trina (Trna, Tri-na):
'Trna' signifies the transfer RNA involved in the biological synthesis of proteins. The discussion around tRNA emphasizes the molecular processes critical to understanding how antiviral peptides can inhibit viral replication.
45) Tree:
'Tree' may allude to biological sources from which therapeutic peptides can be extracted, highlighting the interconnectedness of biodiversity and medicinal applications in pharmaceutical research.
46) Rich (Rch):
'Rich' denotes abundance, potentially in reference to the varieties of antimicrobial peptides explored in the study. It underscores the diversity and availability of natural products that can be harnessed for drug development.
47) Wall:
'Wall' indicates cellular structures, particularly in terms of microbial physiology where peptides may exert antimicrobial actions. Understanding cell wall interactions is vital to therapeutic success.
48) Line:
'Line' may refer to specific sequences or pathways within molecular structures or biological processes critical for facilitating interactions between antimicrobial peptides, viruses, and host cells.