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Advances in Research of Short Peptides II
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Advances in Research of Short Peptides II

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (1 December 2023) | Viewed by 69029

Special Issue Editors

Prof. Dr. Vasso Apostolopoulos

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Guest Editor
Institute for Health and Sport, Victoria University, Melbourne, VIC 3011, Australia
Interests: immunology; protein crystallography; medicinal chemistry; cellular and molecular biology; extensive translational research; clinical trials; vaccines; drugs; healthy ageing; chronic diseases; inflammation
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Dr. Joanna Bojarska

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Guest Editor
Institute of General and Ecological Chemistry, Faculty of Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland
Interests: bio-supramolecular chemistry of oligopeptides; polymorphism; biologically active substances; drug design
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Dr. Tsun-Thai Chai

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Guest Editor
Department of Chemical Science, Faculty of Science, Universiti Tunku Abdul Rahman, Kampar 31900, Malaysia
Interests: antioxidant; bioactive peptide; phytochemicals; molecular docking; antiglucosidase; Medicinal plants; in silico; virtual screening; computational screening; natural products; nutraceutical; plant stress; antioxidative enzymes; proteins
Dr. Jack Feehan

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Guest Editor
Institute for Health and Sport, Victoria University, Melbourne, VIC 3030, Australia
Interests: immunology; inflammation; vaccines; chronic diseases; autoimmune diseases; brain diseases; ageing diseases; healthy ageing; bio-actives; metabolic disorders
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Dr. Krzysztof Kaczmarek

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Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, ̇Zeromskiego 116, 90-924 Lodz, Poland
Interests: peptide chemistry; peptide synthesis; unusual amino acids; peptide bond motifs
Dr. Octavio Paredes-López

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Guest Editor
Center for Research and Advanced Studies of the National Polytechnic Institute, Irapuato, Mexico
Interests: understanding of metabolic processes and their relation to plant human nutrition; modification of metabolic processes to improve nutrition potential of plants for human beings; nutraceutical messages of plants and their fruits
Prof. Dr. Michele Saviano

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Guest Editor
Institute of Crystallography (CNR), URT Caserta, Viale A Lincoln 5, 81100 Caserta, Italy
Interests: biocrystallography, drug design; peptide chemistry
Dr. Mariusz Skwarczynski

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Guest Editor
School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072, Australia
Interests: vaccines and nanomedicine; vaccine design; nanotechnology; peptide chemistry; medicinal chemistry; vaccine/drug delivery; antimicrobial agents; macromolecules; adjuvants; immunology
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Dr. Jillian Smith-Carpenter

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Guest Editor
Department of Chemistry and Biochemistry, Fairfield University, 1073 N. Benson Rd, Fairfield, CT 06824, USA
Interests: self-assembling peptides
Dr. Mariano Venanzi

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Guest Editor
Department of Chemical Science and Technologies, University of Rome Tor Vergata, Via della Ricerca Scientifica 1, 00133 Rome, Italy
Interests: peptide and protein nanotechnology; peptide materials; spectroscopy of biomolecules; peptide self-assembly; porphyrin aggregation and nanostructures
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Prof. Dr. Wojciech M. Wolf

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Guest Editor
Institute of General and Ecological Chemistry, Faculty of Chemistry, Lodz University of Technology, ̇Zeromskiego 116, 90-924 Lodz, Poland
Interests: X-ray crystallography; supramolecular chemistry; crystal engineering; peptides; medicinal chemistry; coordination chemistry; solid-state synthesis; analytical chemistry
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Prof. Dr. Piotr Zielenkiewicz

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Guest Editor
1. Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5a, 02-106 Warsaw, Poland
2. Department of Systems Biology, Institute of Experimental Plant Biology and Biotechnology, University of Warsaw, Miecznikowa 1, 02-096 Warsaw, Poland
Interests: protein structure; bioinformatics; interaction networks; systems medicine
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Dr. Zyta M. Ziora

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Institute for Molecular Bioscience (IMB), The University of Queensland, Saint. Lucia, QLD 4072, Australia
Interests: green synthesis; metal nanoparticles; antimicrobial agents; synergism; wound healing
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Prof. Dr. John Matsoukas

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NewDrug, Patras Science Park, Patras, Greece
Interests: medicinal chemistry; autoimmunity; NMR; modelling; organic chemistry
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Special Issue Information

Dear Colleagues,

We are releasing a second edition of the Special Issue on “Advances in Research of Short Peptides”, and will provide new studies on these amazing molecules that show outstanding structural and functional variety, from proteins to small chemical compounds. In recent years, the interest in short peptides has been remarkable, as was reflected in the first edition of this Special Issue. The first edition comprised 26 informative articles regarding peptides in health and disease. The COVID-19 pandemic has reshaped diverse fields of science and biotechnologies that will have an influence on the unlimited possibilities and applications of short peptides in the future. We are witnessing an evolving growth in biomedicine and beyond, in which short peptides are key players. In this regard, Molecules is delighted to present cutting-edge discoveries, uses and progress of short peptides in this forthcoming second edition of this Special Issue.

Researchers from different fields from all over the world are invited to submit original experimental papers; theoretical uses of peptides; as well as reviews, communications, reports, and notes on short peptide (peptidomimetic)-based research topics.

We invite you to contribute to this Issue, and look forward to your valuable contributions.

Prof. Dr. Vasso Apostolopoulos
Dr. Joanna Bojarska
Dr. Tsun-Thai Chai
Dr. Jack Feehan
Dr. Krzysztof Kaczmarek
Dr. Octavio Paredes-López
Prof. Dr. Michele Saviano
Dr. Mariusz Skwarczynski
Dr. Jillian Smith-Carpenter
Prof. Dr. Mariano Venanzi
Prof. Dr. Wojciech M. Wolf
Prof. Dr. Piotr Zielenkiewicz
Dr. Zyta M. Ziora
Prof. Dr. John Matsoukas
Guest Editors

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.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • peptides
  • oligopeptide-based therapeutic agents and functional biomaterials
  • molecular and supramolecular features
  • drug design
  • drug-receptor interactions
  • synthesis of oligopeptides and modified amino acids

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Related Special Issue

Published Papers (10 papers)

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Editorial

Jump to: Research, Review

4 pages, 198 KiB  
Editorial
New Advances in Short Peptides: Looking Forward
by Vasso Apostolopoulos, Joanna Bojarska, Tsun-Thai Chai, Jack Feehan, Krzysztof Kaczmarek, John M. Matsoukas, Octavio Paredes Lopez, Michele Saviano, Mariusz Skwarczynski, Jillian Smith-Carpenter, Mariano Venanzi, Wojciech M. Wolf, Piotr Zielenkiewicz and Zyta M. Ziora
Molecules 2022, 27(11), 3635; https://doi.org/10.3390/molecules27113635 - 6 Jun 2022
Cited by 9 | Viewed by 2540
Abstract
It is beyond doubt that short peptides hold significant promise in bio-medicine, as the most versatile molecules, both structurally and functionally [...] Full article
(This article belongs to the Special Issue Advances in Research of Short Peptides II)

Research

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17 pages, 4520 KiB  
Article
Flow-Based Fmoc-SPPS Preparation and SAR Study of Cathelicidin-PY Reveals Selective Antimicrobial Activity
by Shama Dissanayake, Junming He, Sung H. Yang, Margaret A. Brimble, Paul W. R. Harris and Alan J. Cameron
Molecules 2023, 28(4), 1993; https://doi.org/10.3390/molecules28041993 - 20 Feb 2023
Cited by 5 | Viewed by 2916
Abstract
Antimicrobial peptides (AMPs) hold promise as novel therapeutics in the fight against multi-drug-resistant pathogens. Cathelicidin-PY (NH2-RKCNFLCKLKEKLRTVITSHIDKVLRPQG-COOH) is a 29-residue disulfide-cyclised antimicrobial peptide secreted as an innate host defence mechanism by the frog Paa yunnanensis (PY) and reported to possess broad-spectrum antibacterial [...] Read more.
Antimicrobial peptides (AMPs) hold promise as novel therapeutics in the fight against multi-drug-resistant pathogens. Cathelicidin-PY (NH2-RKCNFLCKLKEKLRTVITSHIDKVLRPQG-COOH) is a 29-residue disulfide-cyclised antimicrobial peptide secreted as an innate host defence mechanism by the frog Paa yunnanensis (PY) and reported to possess broad-spectrum antibacterial and antifungal properties, exhibiting low cytotoxic and low hemolytic activity. Herein, we detail the total synthesis of cathelicidin-PY using an entirely on-resin synthesis, including assembly of the linear sequence by rapid flow Fmoc-SPPS and iodine-mediated disulfide bridge formation. By optimising a synthetic strategy to prepare cathelicidin-PY, this strategy was subsequently adapted to prepare a bicyclic head-to-tail cyclised derivative of cathelicidin-PY. The structure-activity relationship (SAR) of cathelicidin-PY with respect to the N-terminally positioned disulfide was further probed by preparing an alanine-substituted linear analogue and a series of lactam-bridged peptidomimetics implementing side chain to side chain cyclisation. The analogues were investigated for antimicrobial activity, secondary structure by circular dichroism (CD), and stability in human serum. Surprisingly, the disulfide bridge emerged as non-essential to antimicrobial activity and secondary structure but was amenable to synthetic modification. Furthermore, the synthetic AMP and multiple analogues demonstrated selective activity towards Gram-negative pathogen E. coli in physiologically relevant concentrations of divalent cations. Full article
(This article belongs to the Special Issue Advances in Research of Short Peptides II)
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20 pages, 5916 KiB  
Article
The Preventive Effect of Specific Collagen Peptides against Dexamethasone-Induced Muscle Atrophy in Mice
by Jieun Oh, Sang Hee Park, Dong Seon Kim, Wooram Choi, Jiwon Jang, Laily Rahmawati, Won Young Jang, Hyun Kyung Lim, Ji Yeon Hwang, Ga Rin Gu, Jeong-Ho Geum, Su-Young Choi, Ji Hye Kim and Jae Youl Cho
Molecules 2023, 28(4), 1950; https://doi.org/10.3390/molecules28041950 - 18 Feb 2023
Cited by 1 | Viewed by 3386
Abstract
Muscle atrophy, also known as muscle wasting, is the thinning of muscle mass due to muscle disuse, aging, or diseases such as cancer or neurological problems. Muscle atrophy is closely related to the quality of life and has high morbidity and mortality. However, [...] Read more.
Muscle atrophy, also known as muscle wasting, is the thinning of muscle mass due to muscle disuse, aging, or diseases such as cancer or neurological problems. Muscle atrophy is closely related to the quality of life and has high morbidity and mortality. However, therapeutic options for muscle atrophy are limited, so studies to develop therapeutic agents for muscle loss are always required. For this study, we investigated how orally administered specific collagen peptides (CP) affect muscle atrophy and elucidated its molecular mechanism using an in vivo model. We treated mice with dexamethasone (DEX) to induce a muscular atrophy phenotype and then administered CP (0.25 and 0.5 g/kg) for four weeks. In a microcomputed tomography analysis, CP (0.5 g/kg) intake significantly increased the volume of calf muscles in mice with DEX-induced muscle atrophy. In addition, the administration of CP (0.25 and 0.5 g/kg) restored the weight of the gluteus maximus and the fiber cross-sectional area (CSA) of the pectoralis major and calf muscles, which were reduced by DEX. CP significantly inhibited the mRNA expression of myostatin and the phosphorylation of Smad2, but it did not affect TGF-β, BDNF, or FNDC5 gene expression. In addition, AKT/mTOR, a central pathway for muscle protein synthesis and related to myostatin signaling, was enhanced in the groups that were administered CP. Finally, CP decreased serum albumin levels and increased TNF-α gene expression. Collectively, our in vivo results demonstrate that CP can alleviate muscle wasting through a multitude of mechanisms. Therefore, we propose CP as a supplement or treatment to prevent muscle atrophy. Full article
(This article belongs to the Special Issue Advances in Research of Short Peptides II)
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6 pages, 554 KiB  
Communication
Variation of Proteolytic Cleavage Sites towards the N-Terminal End of the S2 Subunit of the Novel SARS-CoV-2 Omicron Sublineage BA.2.12.1
by Nadine Anna Schilling, Hubert Kalbacher and Timo Burster
Molecules 2022, 27(18), 5817; https://doi.org/10.3390/molecules27185817 - 8 Sep 2022
Cited by 2 | Viewed by 1608
Abstract
The prevalence of novel SARS-CoV-2 variants is also accompanied by an increased turnover rate and additional cleavage sites at the positions necessary for priming the Spike (S) protein. Of these priming sites, the proteolytically sensitive polybasic sequence of the activation loop at the [...] Read more.
The prevalence of novel SARS-CoV-2 variants is also accompanied by an increased turnover rate and additional cleavage sites at the positions necessary for priming the Spike (S) protein. Of these priming sites, the proteolytically sensitive polybasic sequence of the activation loop at the S1/S2 interface and the S2′ location within the S2 subunit of the S protein are cleaved by furin and TMPRSS2, which are important for the infection of the target cell. Neutrophils, migrating to the site of infection, secrete serine proteases to fight against pathogens. The serine proteases encompass neutrophil elastase (NE), proteinase 3 (PR3), and cathepsin G (CatG), which can hydrolyze the peptide bond adjacent to the S1/S2 interface. SARS-CoV-2 might take the opportunity to hijack proteases from an immune response to support viral entry to the cell. The region near S704L within the S2 subunit, a novel amino acid substitution of SARS-CoV-2 Omicron sublineage BA.2.12.1, is located close to the S1/S2 interface. We found that NE, PR3, and CatG digested the peptide within this region; however, the S704L amino acid substitution altered cleavage sites for PR3. In conclusion, such an amino acid substitution modifies S2 antigen processing and might further impact the major histocompatibility complex (MHC) binding and T cell activation. Full article
(This article belongs to the Special Issue Advances in Research of Short Peptides II)
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14 pages, 3048 KiB  
Article
5-Amino-3-methyl-Isoxazole-4-carboxylic Acid as a Novel Unnatural Amino Acid in the Solid Phase Synthesis of α/β-Mixed Peptides
by Urszula Bąchor, Agnieszka Lizak, Remigiusz Bąchor and Marcin Mączyński
Molecules 2022, 27(17), 5612; https://doi.org/10.3390/molecules27175612 - 31 Aug 2022
Cited by 3 | Viewed by 2407
Abstract
The hybrid peptides consisting of α and β-amino acids show great promise as peptidomimetics that can be used as therapeutic agents. Therefore, the development of new unnatural amino acids and the methods of their incorporation into the peptide chain is an important task. [...] Read more.
The hybrid peptides consisting of α and β-amino acids show great promise as peptidomimetics that can be used as therapeutic agents. Therefore, the development of new unnatural amino acids and the methods of their incorporation into the peptide chain is an important task. Here, we described our investigation of the possibility of 5-amino-3-methyl-isoxazole-4-carboxylic acid (AMIA) application in the solid phase peptide synthesis. This new unnatural β-amino acid, presenting various biological activities, was successfully coupled to a resin-bound peptide using different reaction conditions, including classical and ultrasonic agitated solid-phase synthesis. All the synthesized compounds were characterized by tandem mass spectrometry. The obtained results present the possibility of the application of this β-amino acid in the synthesis of a new class of bioactive peptides. Full article
(This article belongs to the Special Issue Advances in Research of Short Peptides II)
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20 pages, 3839 KiB  
Article
Actions of Novel Angiotensin Receptor Blocking Drugs, Bisartans, Relevant for COVID-19 Therapy: Biased Agonism at Angiotensin Receptors and the Beneficial Effects of Neprilysin in the Renin Angiotensin System
by Graham J. Moore, Harry Ridgway, Konstantinos Kelaidonis, Christos T. Chasapis, Irene Ligielli, Thomas Mavromoustakos, Joanna Bojarska and John M. Matsoukas
Molecules 2022, 27(15), 4854; https://doi.org/10.3390/molecules27154854 - 29 Jul 2022
Cited by 7 | Viewed by 2551
Abstract
Angiotensin receptor blockers (ARBs) used in the treatment of hypertension and potentially in SARS-CoV-2 infection exhibit inverse agonist effects at angiotensin AR1 receptors, suggesting the receptor may have evolved to accommodate naturally occurring angiotensin ‘antipeptides’. Screening of the human genome has identified a [...] Read more.
Angiotensin receptor blockers (ARBs) used in the treatment of hypertension and potentially in SARS-CoV-2 infection exhibit inverse agonist effects at angiotensin AR1 receptors, suggesting the receptor may have evolved to accommodate naturally occurring angiotensin ‘antipeptides’. Screening of the human genome has identified a peptide (EGVYVHPV) encoded by mRNA, complementary to that encoding ANG II itself, which is an inverse agonist. Thus, opposite strands of DNA encode peptides with opposite effects at AR1 receptors. Agonism and inverse agonism at AR1 receptors can be explained by a receptor ‘switching’ between an activated state invoking receptor dimerization/G protein coupling and an inverse agonist state mediated by an alternative/second messenger that is slow to reverse. Both receptor states appear to be driven by the formation of the ANG II charge-relay system involving TyrOH-His/imidazole-Carboxylate (analogous to serine proteases). In this system, tyrosinate species formed are essential for activating AT1 and AT2 receptors. ANGII is also known to bind to the zinc-coordinated metalloprotease angiotensin converting enzyme 2 (ACE2) used by the COVID-19 virus to enter cells. Here we report in silico results demonstrating the binding of a new class of anionic biphenyl-tetrazole sartans (‘Bisartans’) to the active site zinc atom of the endopeptidase Neprilysin (NEP) involved in regulating hypertension, by modulating humoral levels of beneficial vasoactive peptides in the RAS such as vasodilator angiotensin (1–7). In vivo and modeling evidence further suggest Bisartans can inhibit ANG II-induced pulmonary edema and may be useful in combatting SARS-CoV-2 infection by inhibiting ACE2-mediated viral entry to cells. Full article
(This article belongs to the Special Issue Advances in Research of Short Peptides II)
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Review

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9 pages, 816 KiB  
Review
Antibody–Biopolymer Conjugates in Oncology: A Review
by Vivek P. Chavda, Pankti C. Balar, Divya Teli, Majid Davidson, Joanna Bojarska and Vasso Apostolopoulos
Molecules 2023, 28(6), 2605; https://doi.org/10.3390/molecules28062605 - 13 Mar 2023
Cited by 14 | Viewed by 2858
Abstract
Cancer is one of the most prevalent diseases and affects a large proportion of the population worldwide. Conventional treatments in the management include chemotherapy, radiotherapy, and surgery. Although being well-accepted, they have many lacunas in the form of severe side effect resulting from [...] Read more.
Cancer is one of the most prevalent diseases and affects a large proportion of the population worldwide. Conventional treatments in the management include chemotherapy, radiotherapy, and surgery. Although being well-accepted, they have many lacunas in the form of severe side effect resulting from lack of targeted delivery. Antibody biopolymer conjugates are a novel method which is an add-on to older methods of immunization. It is used in various diseases and disorders. It ensures the targeted delivery of molecules to increase its efficacy and reduce unwanted effects of the molecule/drug to normal cells. It shows miraculous results in the treatment and management of several cancers even in advanced stages. Herein, we present the chemistry between biopolymer and antibody, their effects on cancer as well as the basic differences between antibody–drug conjugates and antibody–biopolymer conjugates. Full article
(This article belongs to the Special Issue Advances in Research of Short Peptides II)
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23 pages, 1944 KiB  
Review
Bioactive Peptide Discovery from Edible Insects for Potential Applications in Human Health and Agriculture
by Yixian Quah, Shi-Ruo Tong, Joanna Bojarska, Katrin Giller, Sheri-Ann Tan, Zyta Maria Ziora, Tuba Esatbeyoglu and Tsun-Thai Chai
Molecules 2023, 28(3), 1233; https://doi.org/10.3390/molecules28031233 - 27 Jan 2023
Cited by 22 | Viewed by 5133
Abstract
In the past decade, there has been fast-growing interest among researchers to discover bioactive peptides from edible insects and to evaluate their potential applications in the management of human, livestock, and plant health. This review summarizes current knowledge of insect-derived peptides and their [...] Read more.
In the past decade, there has been fast-growing interest among researchers to discover bioactive peptides from edible insects and to evaluate their potential applications in the management of human, livestock, and plant health. This review summarizes current knowledge of insect-derived peptides and their potential role in tackling human health issues and solving agriculture problems by protecting crops and livestock against their pathogens. Numerous bioactive peptides have been identified from edible insect species, including peptides that were enzymatically liberated from insect proteins and endogenous peptides that occur naturally in insects. The peptides exhibited diverse bioactivities, encompassing antioxidant, anti-angiotensin-converting enzyme, anti-dipeptidyl peptidase-IV, anti-glucosidase, anti-lipase, anti-lipoxygenase, anti-cyclooxygenase, anti-obesity, and hepatoprotective activities. Such findings point to their potential contribution to solving human health problems related to inflammation, free radical damage, diabetes, hypertension, and liver damage, among others. Although most of the experiments were performed in vitro, evidence for the in vivo efficacy of some peptides is emerging. Evidence of the protective effects of insect-derived endogenous antimicrobial peptides in combating farm animal and plant pathogens is available. The ability of insect-derived endogenous neuropeptides to protect plants against herbivorous insects has been demonstrated as well. Nevertheless, the potency of peptides identified from insect protein hydrolysates in modulating livestock and plant health remains a knowledge gap to be filled. Full article
(This article belongs to the Special Issue Advances in Research of Short Peptides II)
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28 pages, 1454 KiB  
Review
Peptide-Drug Conjugates: A New Hope for Cancer Management
by Vivek P. Chavda, Hetvi K. Solanki, Majid Davidson, Vasso Apostolopoulos and Joanna Bojarska
Molecules 2022, 27(21), 7232; https://doi.org/10.3390/molecules27217232 - 25 Oct 2022
Cited by 45 | Viewed by 7933
Abstract
Cancer remains the leading cause of death worldwide despite advances in treatment options for patients. As such, safe and effective therapeutics are required. Short peptides provide advantages to be used in cancer management due to their unique properties, amazing versatility, and progress in [...] Read more.
Cancer remains the leading cause of death worldwide despite advances in treatment options for patients. As such, safe and effective therapeutics are required. Short peptides provide advantages to be used in cancer management due to their unique properties, amazing versatility, and progress in biotechnology to overcome peptide limitations. Several appealing peptide-based therapeutic strategies have been developed. Here, we provide an overview of peptide conjugates, the better equivalents of antibody-drug conjugates, as the next generation of drugs for required precise targeting, enhanced cellular permeability, improved drug selectivity, and reduced toxicity for the efficient treatment of cancers. We discuss the basic components of drug conjugates and their release action, including the release of cytotoxins from the linker. We also present peptide-drug conjugates under different stages of clinical development as well as regulatory and other challenges. Full article
(This article belongs to the Special Issue Advances in Research of Short Peptides II)
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10 pages, 1270 KiB  
Review
Tirzepatide, a New Era of Dual-Targeted Treatment for Diabetes and Obesity: A Mini-Review
by Vivek P. Chavda, Jinal Ajabiya, Divya Teli, Joanna Bojarska and Vasso Apostolopoulos
Molecules 2022, 27(13), 4315; https://doi.org/10.3390/molecules27134315 - 5 Jul 2022
Cited by 81 | Viewed by 35747
Abstract
The prevalence of obesity and diabetes is an increasing global problem, especially in developed countries, and is referred to as the twin epidemics. As such, advanced treatment approaches are needed. Tirzepatide, known as a ‘twincretin’, is a ‘first-in-class’ and the only dual glucagon-like [...] Read more.
The prevalence of obesity and diabetes is an increasing global problem, especially in developed countries, and is referred to as the twin epidemics. As such, advanced treatment approaches are needed. Tirzepatide, known as a ‘twincretin’, is a ‘first-in-class’ and the only dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) receptor agonist, that can significantly reduce glycemic levels and improve insulin sensitivity, as well as reducing body weight by more than 20% and improving lipid metabolism. This novel anti-diabetic drug is a synthetic peptide analog of the human GIP hormone with a C20 fatty-diacid portion attached which, via acylation technology, can bind to albumin in order to provide a dose of the drug, by means of subcutaneous injection, once a week, which is appropriate to its a half-life of about five days. Tirzepatide, developed by Eli Lilly, was approved, under the brand name Mounjaro, by the United States Food and Drug Administration in May 2022. This started the ‘twincretin’ era of enormously important and appealing dual therapeutic options for diabetes and obesity, as well as advanced management of closely related cardiometabolic settings, which constitute the leading cause of morbidity, disability, and mortality worldwide. Herein, we present the key characteristics of tirzepatide in terms of synthesis, structure, and activity, bearing in mind its advantages and shortcomings. Furthermore, we briefly trace the evolution of this kind of medical agent and discuss the development of clinical studies. Full article
(This article belongs to the Special Issue Advances in Research of Short Peptides II)
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