scholarly journals Recent Applications of Retro-Inverso Peptides

2021 ◽  
Vol 22 (16) ◽  
pp. 8677
Author(s):  
Nunzianna Doti ◽  
Mario Mardirossian ◽  
Annamaria Sandomenico ◽  
Menotti Ruvo ◽  
Andrea Caporale
Keyword(s):  
Amino Acids ◽  
Neurodegenerative Diseases ◽  
De Novo ◽  
3D Structure ◽  
New Drugs ◽  
Side Chains ◽  
Pros And Cons ◽  
Endogenous Proteases ◽  
Natural Amino Acids ◽  
Poor Stability

Natural and de novo designed peptides are gaining an ever-growing interest as drugs against several diseases. Their use is however limited by the intrinsic low bioavailability and poor stability. To overcome these issues retro-inverso analogues have been investigated for decades as more stable surrogates of peptides composed of natural amino acids. Retro-inverso peptides possess reversed sequences and chirality compared to the parent molecules maintaining at the same time an identical array of side chains and in some cases similar structure. The inverted chirality renders them less prone to degradation by endogenous proteases conferring enhanced half-lives and an increased potential as new drugs. However, given their general incapability to adopt the 3D structure of the parent peptides their application should be careful evaluated and investigated case by case. Here, we review the application of retro-inverso peptides in anticancer therapies, in immunology, in neurodegenerative diseases, and as antimicrobials, analyzing pros and cons of this interesting subclass of molecules.

De Novo Design of a Bolaamphiphilic Peptide with Only Natural Amino Acids

2008 ◽  
Vol 8 (11) ◽  
pp. 1053-1059 ◽  
Author(s):  
Feng Qiu ◽  
Yongzhu Chen ◽  
Chengkang Tang ◽  
Qinghan Zhou ◽  
Chen Wang ◽  
...  
Keyword(s):  
Amino Acids ◽  
De Novo ◽  
De Novo Design ◽  
Natural Amino Acids

scholarly journals Amalgamation of 3D structure and sequence information for protein–protein interaction prediction

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Kanchan Jha ◽  
Sriparna Saha
Keyword(s):  
Amino Acids ◽  
Deep Learning ◽  
Protein Interactions ◽  
3D Structure ◽  
Protein Sequences ◽  
Building Blocks ◽  
New Drugs ◽  
Sequence Information ◽  
Protein Protein Interactions ◽  
Structure Information

Abstract Protein is the primary building block of living organisms. It interacts with other proteins and is then involved in various biological processes. Protein–protein interactions (PPIs) help in predicting and hence help in understanding the functionality of the proteins, causes and growth of diseases, and designing new drugs. However, there is a vast gap between the available protein sequences and the identification of protein–protein interactions. To bridge this gap, researchers proposed several computational methods to reveal the interactions between proteins. These methods merely depend on sequence-based information of proteins. With the advancement of technology, different types of information related to proteins are available such as 3D structure information. Nowadays, deep learning techniques are adopted successfully in various domains, including bioinformatics. So, current work focuses on the utilization of different modalities, such as 3D structures and sequence-based information of proteins, and deep learning algorithms to predict PPIs. The proposed approach is divided into several phases. We first get several illustrations of proteins using their 3D coordinates information, and three attributes, such as hydropathy index, isoelectric point, and charge of amino acids. Amino acids are the building blocks of proteins. A pre-trained ResNet50 model, a subclass of a convolutional neural network, is utilized to extract features from these representations of proteins. Autocovariance and conjoint triad are two widely used sequence-based methods to encode proteins, which are used here as another modality of protein sequences. A stacked autoencoder is utilized to get the compact form of sequence-based information. Finally, the features obtained from different modalities are concatenated in pairs and fed into the classifier to predict labels for protein pairs. We have experimented on the human PPIs dataset and Saccharomyces cerevisiae PPIs dataset and compared our results with the state-of-the-art deep-learning-based classifiers. The results achieved by the proposed method are superior to those obtained by the existing methods. Extensive experimentations on different datasets indicate that our approach to learning and combining features from two different modalities is useful in PPI prediction.

scholarly journals De Novo designed 13 mer hairpin-peptide arrests insulin and inhibits its aggregation: role of OH–π interactions between water and hydrophobic amino acids

RSC Advances ◽  
2020 ◽  
Vol 10 (25) ◽  
pp. 14991-14999
Author(s):  
Meghomukta Mukherjee ◽  
Nilanjan Banerjee ◽  
Subhrangsu Chatterjee
Keyword(s):  
Amino Acids ◽  
Neurodegenerative Diseases ◽  
Type Ii Diabetes ◽  
De Novo ◽  
Prion Diseases ◽  
Cellular Systems ◽  
Type Ii ◽  
P Protein ◽  
Hydrophobic Amino Acids

Protein aggregation in the cellular systems can be highly fatal causing a series of diseases including neurodegenerative diseases like ALS, Alzheimer, Prion Diseases, Parkinson's and other diseases like type II diabetes.

scholarly journals Modification and de novo design of non-ribosomal peptide synthetases (NRPS) using specific assembly points within condensation domains

2018 ◽  
Author(s):  
Kenan A. J. Bozhüyük ◽  
Annabell Linck ◽  
Andreas Tietze ◽  
Frank Wesche ◽  
Sarah Nowak ◽  
...  
Keyword(s):  
Amino Acids ◽  
De Novo ◽  
Covalent Binding ◽  
Efficient Production ◽  
Diverse Range ◽  
Peptide Synthetases ◽  
Catalytically Active ◽  
Peptide Derivatives ◽  
Natural Amino Acids ◽  
Exchange Unit

AbstractMany important natural products are produced by non-ribosomal peptide synthetases (NRPSs) 1.These giant enzyme machines activate amino acids in an assembly line fashion in which a set of catalytically active domains is responsible for the section, activation, covalent binding and connection of a specific amino acid to the growing peptide chain 1,2. Since NRPS are not restricted to the incorporation of the 20 proteinogenic amino acids, their efficient manipulation would give access to a diverse range of peptides available biotechnologically. Here we describe a new fusion point inside condensation (C) domains of NRPSs that enables the efficient production of peptides, even containing non-natural amino acids, in yields higher than 280 mg/L. The technology called eXchange Unit 2.0 (XU2.0) also allows the generation of targeted peptide libraries and therefore might be suitable for the future identification of bioactive peptide derivatives for pharmaceutical and other applications.

d-Amino acids in antimicrobial peptides: a potential approach to treat and combat antimicrobial resistance

2020 ◽  
pp. 1-19
Author(s):  
Shikha Kapil ◽  
Vipasha Sharma
Keyword(s):  
Amino Acids ◽  
Antimicrobial Resistance ◽  
Antimicrobial Peptides ◽  
De Novo ◽  
Wide Spectrum ◽  
New Drugs ◽  
Novel Treatments ◽  
Gram Positive Bacteria ◽  
Increasing Demand ◽  
Bacteria And Fungi

Antimicrobial resistance is one of the leading challenges in the human healthcare segment. Advances in antimicrobial resistance have triggered exploration of natural alternatives to stabilize its seriousness. Antimicrobial peptides are small, positively charged oligopeptides that are as potent as commercially available antibiotics against a wide spectrum of organisms, such as Gram-positive bacteria, Gram-negative bacteria, viruses, and fungal strains. In addition to their antibiotic capabilities, these peptides possess anticancer activity, activate the immune response, and regulate inflammation. Peptides have distinct modes of action and fall into various categories due to their amino acid composition. Although antimicrobial peptides specifically target the bacterial cytoplasmic membrane, they can also target the cell nucleus and protein synthesis. Owing to the increasing demand for novel treatments against the threat of antimicrobial resistance, naturally synthesized peptides are a beneficial development concept. Antimicrobial peptides are pervasive and can easily be modified using de-novo synthesis technology. Antimicrobial peptides can be isolated from natural resources such as humans, plants, bacteria, and fungi. This review gives a brief overview of antimicrobial peptides and their diastereomeric composition. Other current trends, the future scope of antimicrobial peptides, and the role of d-amino acids are also discussed, with a specific emphasis on the design and development of new drugs.

scholarly journals Dehydropeptide Supramolecular Hydrogels and Nanostructures as Potential Peptidomimetic Biomedical Materials

2021 ◽  
Vol 22 (5) ◽  
pp. 2528
Author(s):  
Peter J. Jervis ◽  
Carolina Amorim ◽  
Teresa Pereira ◽  
José A. Martins ◽  
Paula M. T. Ferreira
Keyword(s):  
Amino Acids ◽  
Biomedical Applications ◽  
Research Area ◽  
Peptide Backbone ◽  
Peptide Conjugates ◽  
Dehydroamino Acids ◽  
Endogenous Proteases ◽  
Future Direction ◽  
Natural Amino Acids ◽  
Peptide Hydrogels

Supramolecular peptide hydrogels are gaining increased attention, owing to their potential in a variety of biomedical applications. Their physical properties are similar to those of the extracellular matrix (ECM), which is key to their applications in the cell culture of specialized cells, tissue engineering, skin regeneration, and wound healing. The structure of these hydrogels usually consists of a di- or tripeptide capped on the N-terminus with a hydrophobic aromatic group, such as Fmoc or naphthalene. Although these peptide conjugates can offer advantages over other types of gelators such as cross-linked polymers, they usually possess the limitation of being particularly sensitive to proteolysis by endogenous proteases. One of the strategies reported that can overcome this barrier is to use a peptidomimetic strategy, in which natural amino acids are switched for non-proteinogenic analogues, such as D-amino acids, β-amino acids, or dehydroamino acids. Such peptides usually possess much greater resistance to enzymatic hydrolysis. Peptides containing dehydroamino acids, i.e., dehydropeptides, are particularly interesting, as the presence of the double bond also introduces a conformational restraint to the peptide backbone, resulting in (often predictable) changes to the secondary structure of the peptide. This review focuses on peptide hydrogels and related nanostructures, where α,β-didehydro-α-amino acids have been successfully incorporated into the structure of peptide hydrogelators, and the resulting properties are discussed in terms of their potential biomedical applications. Where appropriate, their properties are compared with those of the corresponding peptide hydrogelator composed of canonical amino acids. In a wider context, we consider the presence of dehydroamino acids in natural compounds and medicinally important compounds as well as their limitations, and we consider some of the synthetic strategies for obtaining dehydropeptides. Finally, we consider the future direction for this research area.

Recent Advances in Drug Repurposing for Parkinson’s Disease

2019 ◽  
Vol 26 (28) ◽  
pp. 5340-5362 ◽  
Author(s):  
Xin Chen ◽  
Giuseppe Gumina ◽  
Kristopher G. Virga
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Drug Discovery ◽  
De Novo ◽  
Drug Repositioning ◽  
Drug Repurposing ◽  
Cost Effective ◽  
New Drugs ◽  
Recent Advances ◽  
Clinical Drugs

:As a long-term degenerative disorder of the central nervous system that mostly affects older people, Parkinson’s disease is a growing health threat to our ever-aging population. Despite remarkable advances in our understanding of this disease, all therapeutics currently available only act to improve symptoms but cannot stop the disease progression. Therefore, it is essential that more effective drug discovery methods and approaches are developed, validated, and used for the discovery of disease-modifying treatments for Parkinson’s disease. Drug repurposing, also known as drug repositioning, or the process of finding new uses for existing or abandoned pharmaceuticals, has been recognized as a cost-effective and timeefficient way to develop new drugs, being equally promising as de novo drug discovery in the field of neurodegeneration and, more specifically for Parkinson’s disease. The availability of several established libraries of clinical drugs and fast evolvement in disease biology, genomics and bioinformatics has stimulated the momentums of both in silico and activity-based drug repurposing. With the successful clinical introduction of several repurposed drugs for Parkinson’s disease, drug repurposing has now become a robust alternative approach to the discovery and development of novel drugs for this disease. In this review, recent advances in drug repurposing for Parkinson’s disease will be discussed.

Natural Products for the Treatment of Neurodegenerative Diseases

2020 ◽  
Vol 27 (34) ◽  
pp. 5790-5828 ◽  
Author(s):  
Ze Wang ◽  
Chunyang He ◽  
Jing-Shan Shi
Keyword(s):  
Nervous System ◽  
Natural Products ◽  
Neurodegenerative Diseases ◽  
Neuroprotective Effect ◽  
Rapid Development ◽  
New Drugs ◽  
Progressive Degeneration ◽  
Cord Injury ◽  
The Central Nervous System ◽  
And Function

Neurodegenerative diseases are a heterogeneous group of disorders characterized by the progressive degeneration of the structure and function of the central nervous system or peripheral nervous system. Alzheimer's Disease (AD), Parkinson's Disease (PD) and Spinal Cord Injury (SCI) are the common neurodegenerative diseases, which typically occur in people over the age of 60. With the rapid development of an aged society, over 60 million people worldwide are suffering from these uncurable diseases. Therefore, the search for new drugs and therapeutic methods has become an increasingly important research topic. Natural products especially those from the Traditional Chinese Medicines (TCMs), are the most important sources of drugs, and have received extensive interest among pharmacist. In this review, in order to facilitate further chemical modification of those useful natural products by pharmacists, we will bring together recent studies in single natural compound from TCMs with neuroprotective effect.

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