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Pharmaceuticals
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Naturally-Occurring Peptides and Proteins as Leads for Drug Discovery and...
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Naturally-Occurring Peptides and Proteins as Leads for Drug Discovery and Development

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

Deadline for manuscript submissions: closed (1 February 2024) | Viewed by 19832

Special Issue Editor

Prof. Dr. Predrag Sikiric

E-Mail Website
Guest Editor
Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Interests: gastrointestinal tract; CNS; cytoprotection; blood vessels; stable gastric pentadecapeptide BPC 157
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The field of endocrinology first emerged with the discovery of secretin, a gut hormone. It was afternoon, 16 January 1902, at University College Hospital, London (United Kingdom). The initial breakthrough was the brisk secretion of pancreatic juice following the irrigation of a denervated loop of small bowel with dilute HCl, accompanied by claims about a chemical messenger released from the acidified intestine to mediate the response. Since this initial report of Bayliss and Starling (J. Physiol. (Lond) 28, 325-353, 1902), and subsequent discoveries (i.e., gastrin), the intention has remained the same: to illustrate the importance of the naturally occurring peptides and proteins as leads for drug discovery and development. However, thanks to these advances, long-term approaches could now be determined with precision. New vistas, new naturally occurring peptides, and new breakthroughs might provide novel insights and improve therapy with novel drug discovery and development. 

Prof. Dr. Predrag Sikiric
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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Keywords

  • naturally occurring peptides
  • drug discovery
  • drug development

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Published Papers (4 papers)

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Research

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28 pages, 15336 KiB  
Article
Immunomodulatory Peptides as Vaccine Adjuvants and Antimicrobial Agents
by Shiva Hemmati, Zahra Saeidikia, Hassan Seradj and Abdolali Mohagheghzadeh
Pharmaceuticals 2024, 17(2), 201; https://doi.org/10.3390/ph17020201 - 2 Feb 2024
Cited by 2 | Viewed by 2433
Abstract
The underdevelopment of adjuvant discovery and diversity, compared to core vaccine technology, is evident. On the other hand, antibiotic resistance is on the list of the top ten threats to global health. Immunomodulatory peptides that target a pathogen and modulate the immune system [...] Read more.
The underdevelopment of adjuvant discovery and diversity, compared to core vaccine technology, is evident. On the other hand, antibiotic resistance is on the list of the top ten threats to global health. Immunomodulatory peptides that target a pathogen and modulate the immune system simultaneously are promising for the development of preventive and therapeutic molecules. Since investigating innate immunity in insects has led to prominent achievements in human immunology, such as toll-like receptor (TLR) discovery, we used the capacity of the immunomodulatory peptides of arthropods with concomitant antimicrobial or antitumor activity. An SVM-based machine learning classifier identified short immunomodulatory sequences encrypted in 643 antimicrobial peptides from 55 foe-to-friend arthropods. The critical features involved in efficacy and safety were calculated. Finally, 76 safe immunomodulators were identified. Then, molecular docking and simulation studies defined the target of the most optimal peptide ligands among all human cell-surface TLRs. SPalf2-453 from a crab is a cell-penetrating immunoadjuvant with antiviral properties. The peptide interacts with the TLR1/2 heterodimer. SBsib-711 from a blackfly is a TLR4/MD2 ligand used as a cancer vaccine immunoadjuvant. In addition, SBsib-711 binds CD47 and PD-L1 on tumor cells, which is applicable in cancer immunotherapy as a checkpoint inhibitor. MRh4-679 from a shrimp is a broad-spectrum or universal immunoadjuvant with a putative Th1/Th2-balanced response. We also implemented a pathway enrichment analysis to define fingerprints or immunological signatures for further in vitro and in vivo immunogenicity and reactogenicity measurements. Conclusively, combinatorial machine learning, molecular docking, and simulation studies, as well as systems biology, open a new opportunity for the discovery and development of multifunctional prophylactic and therapeutic lead peptides. Full article
(This article belongs to the Special Issue Naturally-Occurring Peptides and Proteins as Leads for Drug Discovery and Development)
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41 pages, 8884 KiB  
Article
Stable Gastric Pentadecapeptide BPC 157 Therapy: Effect on Reperfusion Following Maintained Intra-Abdominal Hypertension (Grade III and IV) in Rats
by Marijan Tepes, Ivan Krezic, Hrvoje Vranes, Ivan Maria Smoday, Luka Kalogjera, Helena Zizek, Vlasta Vukovic, Katarina Oroz, Katarina Kasnik Kovac, Zrinko Madzar, Mislav Rakic, Blazenka Miskic, Suncana Sikiric, Ivan Barisic, Sanja Strbe, Marko Antunovic, Luka Novosel, Ivana Kavelj, Josipa Vlainic, Ivan Dobric, Mario Staresinic, Anita Skrtic, Sven Seiwerth, Alenka Boban Blagaic and Predrag Sikiricadd Show full author list remove Hide full author list
Pharmaceuticals 2023, 16(11), 1554; https://doi.org/10.3390/ph16111554 - 2 Nov 2023
Cited by 4 | Viewed by 1558
Abstract
Given in reperfusion, the use of stable gastric pentadecapeptide BPC 157 is an effective therapy in rats. It strongly counteracted, as a whole, decompression/reperfusion-induced occlusion/occlusion-like syndrome following the worst circumstances of acute abdominal compartment and intra-abdominal hypertension, grade III and grade IV, as [...] Read more.
Given in reperfusion, the use of stable gastric pentadecapeptide BPC 157 is an effective therapy in rats. It strongly counteracted, as a whole, decompression/reperfusion-induced occlusion/occlusion-like syndrome following the worst circumstances of acute abdominal compartment and intra-abdominal hypertension, grade III and grade IV, as well as compression/ischemia-occlusion/occlusion-like syndrome. Before decompression (calvariectomy, laparotomy), rats had long-lasting severe intra-abdominal hypertension, grade III (25 mmHg/60 min) (i) and grade IV (30 mmHg/30 min; 40 mmHg/30 min) (ii/iii), and severe occlusion/occlusion-like syndrome. Further worsening was caused by reperfusion for 60 min (i) or 30 min (ii/iii). Severe vascular and multiorgan failure (brain, heart, liver, kidney, and gastrointestinal lesions), widespread thrombosis (peripherally and centrally) severe arrhythmias, intracranial (superior sagittal sinus) hypertension, portal and caval hypertension, and aortal hypotension were aggravated. Contrarily, BPC 157 therapy (10 µg/kg, 10 ng/kg sc) given at 3 min reperfusion times eliminated/attenuated venous hypertension (intracranial (superior sagittal sinus), portal, and caval) and aortal hypotension and counteracted the increases in organ lesions and malondialdehyde values (blood ˃ heart, lungs, liver, kidney ˃ brain, gastrointestinal tract). Vascular recovery promptly occurred (i.e., congested inferior caval and superior mesenteric veins reversed to the normal vessel presentation, the collapsed azygos vein reversed to a fully functioning state, the inferior caval vein–superior caval vein shunt was recovered, and direct blood delivery returned). BPC 157 therapy almost annihilated thrombosis and hemorrhage (i.e., intracerebral hemorrhage) as proof of the counteracted general stasis and Virchow triad circumstances and reorganized blood flow. In conclusion, decompression/reperfusion-induced occlusion/occlusion-like syndrome counteracted by BPC 157 therapy in rats is likely for translation in patients. It is noteworthy that by rapidly counteracting the reperfusion course, it also reverses previous ischemia-course lesions, thus inducing complete recovery. Full article
(This article belongs to the Special Issue Naturally-Occurring Peptides and Proteins as Leads for Drug Discovery and Development)
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20 pages, 5516 KiB  
Article
Computational Discovery of Marine Molecules of the Cyclopeptide Family with Therapeutic Potential
by Norma Flores-Holguín, Joan S. Salas-Leiva and Daniel Glossman-Mitnik
Pharmaceuticals 2023, 16(10), 1377; https://doi.org/10.3390/ph16101377 - 28 Sep 2023
Cited by 1 | Viewed by 902
Abstract
Stellatolides are natural compounds that have shown promising biological activities, including antitumor, antimicrobial, and anti-inflammatory properties, making them potential candidates for drug development. Chemical Reactivity Theory (CRT) is a branch of chemistry that explains and predicts the behavior of chemical reactions based on [...] Read more.
Stellatolides are natural compounds that have shown promising biological activities, including antitumor, antimicrobial, and anti-inflammatory properties, making them potential candidates for drug development. Chemical Reactivity Theory (CRT) is a branch of chemistry that explains and predicts the behavior of chemical reactions based on the electronic structure of molecules. Conceptual Density Functional Theory (CDFT) and Computational Peptidology (CP) are computational approaches used to study the behavior of atoms, molecules, and peptides. In this study, we present the results of our investigation of the chemical reactivity and ADMET properties of Stellatolides A-H using a novel computational approach called Conceptual DFT-based Computational Peptidology (CDFT-CP). Our study uses CDFT and CP to predict the reactivity and stability of molecules and to understand the behavior of peptides at the molecular level. We also predict the ADMET properties of the Stellatolides A–H to provide insight into their effectiveness, potential side effects, and optimal dosage and route of administration, as well as their biological targets. This study sheds light on the potential of Stellatolides A–H as promising candidates for drug development and highlights the potential of CDFT-CP for the study of other natural compounds and peptides. Full article
(This article belongs to the Special Issue Naturally-Occurring Peptides and Proteins as Leads for Drug Discovery and Development)
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Review

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30 pages, 616 KiB  
Review
Stable Gastric Pentadecapeptide BPC 157 May Recover Brain–Gut Axis and Gut–Brain Axis Function
by Predrag Sikiric, Slaven Gojkovic, Ivan Krezic, Ivan Maria Smoday, Luka Kalogjera, Helena Zizek, Katarina Oroz, Hrvoje Vranes, Vlasta Vukovic, May Labidi, Sanja Strbe, Lidija Baketic Oreskovic, Marko Sever, Marijan Tepes, Mario Knezevic, Ivan Barisic, Vladimir Blagaic, Josipa Vlainic, Ivan Dobric, Mario Staresinic, Anita Skrtic, Ivana Jurjevic, Alenka Boban Blagaic and Sven Seiwerthadd Show full author list remove Hide full author list
Pharmaceuticals 2023, 16(5), 676; https://doi.org/10.3390/ph16050676 - 30 Apr 2023
Cited by 9 | Viewed by 14400
Abstract
Conceptually, a wide beneficial effect, both peripherally and centrally, might have been essential for the harmony of brain–gut and gut–brain axes’ function. Seen from the original viewpoint of the gut peptides’ significance and brain relation, the favorable stable gastric pentadecapeptide BPC 157 evidence [...] Read more.
Conceptually, a wide beneficial effect, both peripherally and centrally, might have been essential for the harmony of brain–gut and gut–brain axes’ function. Seen from the original viewpoint of the gut peptides’ significance and brain relation, the favorable stable gastric pentadecapeptide BPC 157 evidence in the brain–gut and gut–brain axes’ function might have been presented as a particular interconnected network. These were the behavioral findings (interaction with main systems, anxiolytic, anticonvulsive, antidepressant effect, counteracted catalepsy, and positive and negative schizophrenia symptoms models). Muscle healing and function recovery appeared as the therapeutic effects of BPC 157 on the various muscle disabilities of a multitude of causes, both peripheral and central. Heart failure was counteracted (including arrhythmias and thrombosis), and smooth muscle function recovered. These existed as a multimodal muscle axis impact on muscle function and healing as a function of the brain–gut axis and gut–brain axis as whole. Finally, encephalopathies, acting simultaneously in both the periphery and central nervous system, BPC 157 counteracted stomach and liver lesions and various encephalopathies in NSAIDs and insulin rats. BPC 157 therapy by rapidly activated collateral pathways counteracted the vascular and multiorgan failure concomitant to major vessel occlusion and, similar to noxious procedures, reversed initiated multicausal noxious circuit of the occlusion/occlusion-like syndrome. Severe intracranial (superior sagittal sinus) hypertension, portal and caval hypertensions, and aortal hypotension were attenuated/eliminated. Counteracted were the severe lesions in the brain, lungs, liver, kidney, and gastrointestinal tract. In particular, progressing thrombosis, both peripherally and centrally, and heart arrhythmias and infarction that would consistently occur were fully counteracted and/or almost annihilated. To conclude, we suggest further BPC 157 therapy applications. Full article
(This article belongs to the Special Issue Naturally-Occurring Peptides and Proteins as Leads for Drug Discovery and Development)
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