A Proline-Based Tectons and Supramolecular Synthons for Drug Design 2.0: A Case Study of ACEI

Bojarska, Joanna; Remko, Milan; Breza, Martin; Madura, Izabela D.; Fruziński, Andrzej; Wolf, Wojciech M.

doi:10.3390/ph13110338

Cited by 14 publications

(14 citation statements)

References 221 publications

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“…Supramolecular chemistry (‘‘chemistry beyond the molecule’’) is a bottom-up approach to the formation of well-ordered structures in the nano- (and the micro-) scale. Their adaptable, controllable, self-healing, and bio-physico-chemical stimuli-responsive properties induced via non-covalent interactions (electrostatic, hydrogen bonding, π–π stacking, van der Waals or hydrophobic) are highly appreciated [ 123 , 127 , 128 , 129 , 130 , 131 , 132 ]. They have the dynamic nature and provide a firm basis for the structure and functioning of living systems.…”

Section: Frontiers and Prospects Of Short Peptidesmentioning

confidence: 99%

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A Global Review on Short Peptides: Frontiers and Perspectives

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Peptides are fragments of proteins that carry out biological functions. They act as signaling entities via all domains of life and interfere with protein-protein interactions, which are indispensable in bio-processes. Short peptides include fundamental molecular information for a prelude to the symphony of life. They have aroused considerable interest due to their unique features and great promise in innovative bio-therapies. This work focusing on the current state-of-the-art short peptide-based therapeutical developments is the first global review written by researchers from all continents, as a celebration of 100 years of peptide therapeutics since the commencement of insulin therapy in the 1920s. Peptide “drugs” initially played only the role of hormone analogs to balance disorders. Nowadays, they achieve numerous biomedical tasks, can cross membranes, or reach intracellular targets. The role of peptides in bio-processes can hardly be mimicked by other chemical substances. The article is divided into independent sections, which are related to either the progress in short peptide-based theranostics or the problems posing challenge to bio-medicine. In particular, the SWOT analysis of short peptides, their relevance in therapies of diverse diseases, improvements in (bio)synthesis platforms, advanced nano-supramolecular technologies, aptamers, altered peptide ligands and in silico methodologies to overcome peptide limitations, modern smart bio-functional materials, vaccines, and drug/gene-targeted delivery systems are discussed.

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Section: Frontiers and Prospects Of Short Peptidesmentioning

confidence: 99%

“…Noteworthily, they have similar pharmacological profile as corresponding drug molecules. They were found in the central nervous system, gastrointestinal tract, and blood [123]. Interestingly, they played a key role in the origin of life [112,124].…”

Section: Ultra-short Peptides: Less Is Morementioning

confidence: 99%

A Global Review on Short Peptides: Frontiers and Perspectives

et al. 2021

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“…Proline-based DKPs have a special characteristic [12]. Proline is a unique amino acid due to its specific structure.…”

Section: Dkp Scaffoldmentioning

confidence: 99%

“…Notably, proline motif introduces additional conformational and bio-functional value into the DKP-derived structures. The attractive features, such as extra rigidity, structural stability, and consequently, greater resistance to degradation by enzymes, higher bioactivity, specificity, selectivity, and efficacy, increased cell permeability, or binding affinity to specific targets, inherent biocompatibility, structural importance to biological systems [11,12] make proline-based cyclic dipeptides a promising alternative to currently used small molecule and macromolecule pharmaceuticals.…”

Section: Introductionmentioning

confidence: 99%

Cyclic Dipeptides: The Biological and Structural Landscape with Special Focus on the Anti-Cancer Proline-Based Scaffold

et al. 2021

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Cyclic dipeptides, also know as diketopiperazines (DKP), the simplest cyclic forms of peptides widespread in nature, are unsurpassed in their structural and bio-functional diversity. DKPs, especially those containing proline, due to their unique features such as, inter alia, extra-rigid conformation, high resistance to enzyme degradation, increased cell permeability, and expandable ability to bind a diverse of targets with better affinity, have emerged in the last years as biologically pre-validated platforms for the drug discovery. Recent advances have revealed their enormous potential in the development of next-generation theranostics, smart delivery systems, and biomaterials. Here, we present an updated review on the biological and structural profile of these appealing biomolecules, with a particular emphasis on those with anticancer properties, since cancers are the main cause of death all over the world. Additionally, we provide a consideration on supramolecular structuring and synthons, based on the proline-based DKP privileged scaffold, for inspiration in the design of compound libraries in search of ideal ligands, innovative self-assembled nanomaterials, and bio-functional architectures.

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“…This work is a continuation of our studies focusing on the paramount goal of supramolecular exploration of biologically active systems, especially short peptides and modified amino acids ( Główka, et al, 2004 ; Główka, et al, 2005 ; Główka, et al, 2007 ; Olczak, et al, 2007 ; Olczak, et al, 2010 ; Remko, et al, 2011 ; Bojarska et al, 2012a ; Bojarska et al, 2012b ; Remko et al, 2013 ; Bojarska et al, 2013a ; Bojarska et al, 2013b ; Bojarska et al, 2013c ; Bojarska et al, 2014 ; Bojarska et al, 2015 ; Bojarska and Maniukiewicz, 2015 ; Remko et al, 2015 ; Bojarska et al, 2016 ; Bojarska et al, 2018a ; Bojarska et al, 2018b ; Bojarska et al, 2019a ; Bojarska et al, 2019b ; Bojarska et al, 2019c ; Bojarska et al, 2019d ; Bojarska et al, 2019e ; Bojarska et al, 2020a ; Bojarska et al, 2020b ; Bojarska et al, 2020c ; Bojarska et al, 2020d ). The article is the first one, according to our knowledge, to gain deep supramolecular insight into the very popular drug DFMO ( 1 ) ( Supplementary Figure S1 ), an ornithine derivative ( Bojarska et al, 2020b ), which is still being developed as a promising broad-spectrum therapeutic agent.…”

Section: Introductionmentioning

confidence: 95%

The First Insight Into the Supramolecular System of D,L-α-Difluoromethylornithine: A New Antiviral Perspective

et al. 2021

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Targeting the polyamine biosynthetic pathway by inhibiting ornithine decarboxylase (ODC) is a powerful approach in the fight against diverse viruses, including SARS-CoV-2. Difluoromethylornithine (DFMO, eflornithine) is the best-known inhibitor of ODC and a broad-spectrum, unique therapeutical agent. Nevertheless, its pharmacokinetic profile is not perfect, especially when large doses are required in antiviral treatment. This article presents a holistic study focusing on the molecular and supramolecular structure of DFMO and the design of its analogues toward the development of safer and more effective formulations. In this context, we provide the first deep insight into the supramolecular system of DFMO supplemented by a comprehensive, qualitative and quantitative survey of non-covalent interactions via Hirshfeld surface, molecular electrostatic potential, enrichment ratio and energy frameworks analysis visualizing 3-D topology of interactions in order to understand the differences in the cooperativity of interactions involved in the formation of either basic or large synthons (Long-range Synthon Aufbau Modules, LSAM) at the subsequent levels of well-organized supramolecular self-assembly, in comparison with the ornithine structure. In the light of the drug discovery, supramolecular studies of amino acids, essential constituents of proteins, are of prime importance. In brief, the same amino-carboxy synthons are observed in the bio-system containing DFMO. DFT calculations revealed that the biological environment changes the molecular structure of DFMO only slightly. The ADMET profile of structural modifications of DFMO and optimization of its analogue as a new promising drug via molecular docking are discussed in detail.

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A Proline-Based Tectons and Supramolecular Synthons for Drug Design 2.0: A Case Study of ACEI

Cited by 14 publications

References 221 publications

A Global Review on Short Peptides: Frontiers and Perspectives

A Global Review on Short Peptides: Frontiers and Perspectives

Cyclic Dipeptides: The Biological and Structural Landscape with Special Focus on the Anti-Cancer Proline-Based Scaffold

The First Insight Into the Supramolecular System of D,L-α-Difluoromethylornithine: A New Antiviral Perspective

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