Non-Natural Amino Acids in Drug Design

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Biopharmaceuticals".

Deadline for manuscript submissions: closed (29 October 2022) | Viewed by 4924

Special Issue Editor


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Guest Editor
Department of Organic Chemistry, University of Chemical Technology and Metallurgy, 1756 Sofia, Bulgaria
Interests: amino acids; peptide chemistry; organic synthesis; organic phosphorus compounds; biological active substances; endogenous peptides; pharmaceutical and medicinal chemistry
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Special Issue Information

Dear Colleagues,

Synthesis, characterization, and biological application of non-natural amino acids and their derivatives is a scientific topic related to the study and development of new therapeutic drugs for future application in medicine. The creation of drugs without toxicity and with fewer side effects is a major problem whose solution is a challenge for scientists from all over the world. This also motivates the scientists to investigate the possibilities for the synthesis or study of new unusual amino acids and their derivatives believed to possess a wide range of biological activity. It is known that the introduction of unnatural amino acids into peptides significantly improves the resistance of the peptide to enzymatic hydrolysis and biological activity. The handling of the amino acidic scaffold can be regarded as a potentially powerful tool in both pharmaceuticals and medicinal chemistry investigations and the development of new drug candidates. For example, the impact of non-natural amino acids incorporation can be highly useful in improving the stability, potency, bioavailability, and others properties of peptide-based therapies. Aminophosphonic acids are considered to be an important class of amino acid mimetics, and can also be assigned to non-natural amino acids. They have impacted a position of eminence in the field of research works aimed at discovery, understanding, and modification of physiological processes in living organisms.

This Special Issue will involve research manuscripts, reviews, as well as short commentaries on topics related to non-natural amino acids and their derivatives in drug design, both in pharmaceutical and medicinal chemistry—from synthesis and characterization to their application as potential therapeutics. It can cover reports from chemistry to biology in the field of unnatural amino acids and peptide therapeutics containing unusual amino acids as well as their medicinal application. The exact mechanism of action of non-proteinogenic amino acids and their derivatives on a number of biological processes and activities performed in living organisms has not yet been fully elucidated. This Special Issue has the aim to summarize the state-of-the-art and the latest findings published in the non-natural amino acids in the drug design field, as well as to elucidate future directions.

Dr. Petar Todorov
Guest Editor

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Keywords

  • non-natural amino acids in pharmaceutical and medicinal chemistry
  • chemical biology of unnatural amino acids
  • drug design
  • unusual amino acids
  • unnatural conformationally restricted amino acids
  • D-amino acids
  • non-proteinogenic amino acids
  • α-Aminophosphonic acids and their derivatives
  • peptide therapeutics containing non-natural amino acids

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Published Papers (2 papers)

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Research

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18 pages, 4644 KiB  
Article
Synthesis, Characterization and Biological Investigation of New N-Modified Spinorphin Analogs
by Petar Todorov, Stela Georgieva, Jana Tchekalarova, Subaer Subaer, Petia Peneva and Hartati Hartati
Pharmaceuticals 2022, 15(10), 1251; https://doi.org/10.3390/ph15101251 - 11 Oct 2022
Cited by 1 | Viewed by 1894
Abstract
The emergence of diverse peptide derivatives has been due to constant efforts to find a specific peptide with pronounced biological activity for effective application as a therapeutic. Spinorphin-peptide products have been reported to possess various applications and properties. In the present study, spinorphin [...] Read more.
The emergence of diverse peptide derivatives has been due to constant efforts to find a specific peptide with pronounced biological activity for effective application as a therapeutic. Spinorphin-peptide products have been reported to possess various applications and properties. In the present study, spinorphin peptides with a rhodamine residue and a modification in the amino acid backbone were synthesized by a solid-phase method using Fmoc chemistry. The results obtained from the spectral and electrochemical techniques used: Scanning electron microscopy (SEM), UV-vis, fluorescence, infrared spectroscopy (IR), and voltammetry were used to elucidate the structural characteristics and some physicochemical properties to gain insight into their behavior in the solid state and in aqueous solutions with different pHs. Both Rh-S5 and Rh-S6 had compound anticonvulsant effect comparable to Rh-S against psychomotor seizures at the highest dose of 20 μg. Furthermore, Rh-S6 showed a strong ability to inhibit seizure propagation and had a similar threshold to Rh-S against the intravenous pentylenetetrazol induced clonic seizure in mice; one of the three hybrid spinorphin analogs tested when screened for anticonvulsant activity. Biological tests against several bacterial pathogens such as Staphylococcus aureus, Escherichia coli, and Bacillus cereus showed similar results to negative control of the new peptide derivatives. The compounds also showed weak activity against Candida albicans fungus. The antioxidant testing results revealed more than 50% activity by reviewing the radical deterrence capabilities of 2,2-diphenyl-1-picrylhydrazyl (DPPH). The results are indicative of the ongoing search for universal antimicrobial agents with pronounced synergism when used simultaneously as anticonvulsant, antibacterial, and antifungal agents. Full article
(This article belongs to the Special Issue Non-Natural Amino Acids in Drug Design)
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Review

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24 pages, 4604 KiB  
Review
Recent Synthesis, Characterization, and Pharmacological Evaluation of Multifunctional Hemorphins Containing Non-Natural Amino Acids with Potential Biological Importance
by Petar Todorov, Stela Georgieva and Jana Tchekalarova
Pharmaceuticals 2022, 15(11), 1425; https://doi.org/10.3390/ph15111425 - 17 Nov 2022
Cited by 4 | Viewed by 1953
Abstract
The endogenous hemorphins are bioactive peptides with activity on opioid receptors. They are extensively studied and summarized in numerous reviews. During the last decade, several research teams have synthesized, characterized, and pharmacologically evaluated synthetic hemorphin analogs containing unusual amino acids, D-amino acids, α-aminophosphonic [...] Read more.
The endogenous hemorphins are bioactive peptides with activity on opioid receptors. They are extensively studied and summarized in numerous reviews. During the last decade, several research teams have synthesized, characterized, and pharmacologically evaluated synthetic hemorphin analogs containing unusual amino acids, D-amino acids, α-aminophosphonic acids, and their derivatives. The present review summarizes the current studies on short-chain synthetic hemorphin peptide derivates containing non-natural amino acids. This review focuses on the structure–activity relationship analysis, details on specific methods for their characterization, and the advantage of synthetic hemorphin analogs compared to endogenous peptides as potent biologically active compounds with a complex mechanism of action. Full article
(This article belongs to the Special Issue Non-Natural Amino Acids in Drug Design)
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