Peptoids and Peptide Based Drugs

Topic Information

Dear Colleagues,

Over the last few decades, peptides have gained increasing interest as attractive drugs due to their unique ability to combine the advantages of antibodies and small molecules and the more favorable specificity and selectivity for their targets. Today, over 80 peptide-based therapeutic agents have been approved by the FDA, and many more are in clinical development. Therapeutic peptides have been identified from various sources, such as living organisms, synthetic chemical libraries, genetic or recombinant libraries, and bioinformatic approaches. They commonly act as hormones, growth factors, neurotransmitters, ion channel ligands, or anti-infective agents, bind to cell surface receptors, and trigger intracellular effects with high affinity and specificity. Recently, the ability of peptides to effectively and selectively inhibit PPIs has also been demonstrated, opening the doors for peptide therapeutics to reach the currently "undruggable" space. Despite these advantages, some peptides still suffer from drawbacks such as poor cellular permeability and high metabolic instability. An attractive alternative that overcomes these challenges is developing peptidomimetics-based therapeutics that are physiologically stable and have high cellular permeability. One class of peptidomimetics, which is an excellent candidate for this purpose, is peptoids, N-substituted glycine oligomers. Peptoids can be synthesized on solid support from primary amines, allowing to introduce a variety of functional groups within their sequence. They can fold into well-defined secondary structures in solution and could be employed in various biological activities, including protein–protein interactions and selective extraction of metal ions. Importantly, peptoids, which cannot form hydrogen bonding because they comprise a tertiary amide backbone, display a significantly improved stability profile in vivo, are more lipophilic than peptides, and have some intriguing pharmacological properties: they are stable against proteases and peptidases, are tolerant towards high salt concentration and various pH conditions, and have better bioavailability and better cell permeability than peptides. Due to these advantages, peptoids are becoming attractive candidates for therapeutic and diagnostic applications. To date, peptoids have demonstrated bioactivity as protein mimics and as replacements for small molecule drugs. Recent advances in research on peptoid as therapeutics in the last several years include in vitro and in vivo studies in the fields of lung surfactant therapy, antimicrobial agents, diagnostics, and anticancer agents and inhibitors. Some of these peptoids are designed de novo, while others are prepared by converting interesting peptides into peptoids. The latter, however, is associated with a reduction in the biological activity related to even minor structural changes, and the development of peptide–peptoid chimeras (peptomers) can help in creating better peptoid-based therapeutics.

Dr. Laura Zaccaro
Dr. Annarita Del Gatto
Dr. Galia Maayan
Topic Editors

Keywords

Participating Journals

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Biomedicines biomedicines	3.9	6.8	2013	21 Days	CHF 2600
Biophysica biophysica	1.4	2.3	2021	15.7 Days	CHF 1200
International Journal of Molecular Sciences ijms	4.9	9.0	2000	17.8 Days	CHF 2900
Journal of Clinical Medicine jcm	2.9	5.2	2012	18.5 Days	CHF 2600
Molecules molecules	4.6	8.6	1996	15.1 Days	CHF 2700
Pharmaceuticals pharmaceuticals	4.8	7.7	2004	16 Days	CHF 2900
Pharmaceutics pharmaceutics	5.5	10.0	2009	15.7 Days	CHF 2900
Pharmacy pharmacy	1.8	-	2013	22.9 Days	CHF 1800

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Published Papers (15 papers)

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Open AccessArticle

Selective Human-Milk-Inspired Antimicrobial Peptides for the Treatment of Bacterial Vaginosis

by Ishita M. Shah, Carlito B. Lebrilla, J. Bruce German and David A. Mills

Pharmaceutics 2026, 18(3), 371; https://doi.org/10.3390/pharmaceutics18030371 - 17 Mar 2026

Viewed by 841

Abstract

Background: Antimicrobial resistance (AMR) is a global healthcare threat. Traditional largely non-selective antibiotics produce side effects due to the natural host microbiome being modified creating a loss in homeostasis. In women, AMR is a cause of acute generational impact. For example, bacterial vaginosis [...] Read more.

Background: Antimicrobial resistance (AMR) is a global healthcare threat. Traditional largely non-selective antibiotics produce side effects due to the natural host microbiome being modified creating a loss in homeostasis. In women, AMR is a cause of acute generational impact. For example, bacterial vaginosis (BV), the most common gynecological infection in reproductive-age women, is a serious public health concern due to its high rates of recurrence, secondary infections, and reproductive issues; and two currently prescribed antibiotics for BV do not fully resolve the symptoms. Objective: The strong need for innovative, potent, safe, and selective therapeutics has prompted a search for such bioactive molecules in milk. Resulting from 200 million years of evolutionary pressure, mammalian lactation not only nourishes infants, but it has also been under relentless Darwinian selective pressure to provide protection from a variety of infections. Methods: Computationally designed human-milk-inspired peptides (AMPs) were tested in standard microbicidal assays for activity against BV pathogens, and evaluated for stability and safety. Results: Several AMPs are bactericidal towards Gardnerella vaginalis, a major BV-associated pathogen, and other BV-associated pathogens. Some novel AMPs do not impact the viability of key lactobacilli linked to a healthy vaginal microbiome. These stable, membrane-acting cationic AMPs reduce inflammation during an infection assay and are safe in EpiVag organoid tissues. Conclusions: AMPs can address concerns like non-selectivity and antibiotic resistance—thereby addressing AMR. Lead AMPs from this study offer a promising solution for the development of novel therapeutics for the treatment of BV, which may reduce the burden of AMR. Full article

(This article belongs to the Topic Peptoids and Peptide Based Drugs)

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23 pages, 14118 KB  

Open AccessArticle

Discovery of Peptide-Based Tubulin Inhibitors Through Structure-Guided Design

by Nicolás Osses-Bagatello, Esteban Rocha-Valderrama, José Ortega-Campos, Mauricio Moncada-Basualto and Matías Zúñiga-Bustos

Pharmaceutics 2026, 18(2), 270; https://doi.org/10.3390/pharmaceutics18020270 - 22 Feb 2026

Viewed by 645

Abstract

Background: Tubulin plays a pivotal role in cell division and other essential cellular processes, making it a key pharmacological target for cancer therapy, antiparasitic treatments, and neurodegenerative diseases. Numerous compounds have been developed to regulate microtubule polymerization through tubulin binding; however, most have [...] Read more.

Background: Tubulin plays a pivotal role in cell division and other essential cellular processes, making it a key pharmacological target for cancer therapy, antiparasitic treatments, and neurodegenerative diseases. Numerous compounds have been developed to regulate microtubule polymerization through tubulin binding; however, most have shown significant limitations, including adverse side effects, poor bioavailability and limited specificity. In recent years, peptide-based therapies have gained considerable attention, particularly for their ability to modulate protein–protein interaction while offering improved selectivity and safety profiles. Methods: In this study, we employed an integrated computational–experimental approach combining molecular docking, molecular dynamics simulations, and MM-GBSA free energy calculations to design and evaluate 14 peptides derived from the αβ-tubulin dimer interface. Results: The peptide NH₂-P14-COOH emerged as the most promising candidate, displaying the stronger inhibition of tubulin polymerization activity (IC₅₀ = 11.24 ± 3.82 μM), selective cytotoxicity against NCI-H1299 lung carcinoma cells (IC₅₀ = 45.64 ± 3.20 μM), and no significant toxicity toward non-cancerous EA.hy926 endothelial cells (IC₅₀ > 100 μM). Flow cytometry analysis confirmed that NH₂-P14-COOH induces apoptosis, supporting a mechanism of action based on microtubule disruption. Conclusions: These findings highlight NH₂-P14-COOH as a selective antimitotic peptide with a favorable therapeutic index and demonstrate the potential of structure-guided peptide design for the development of novel microtubule-targeting agents with reduced off-target toxicity. Full article

(This article belongs to the Topic Peptoids and Peptide Based Drugs)

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11 pages, 879 KB  

Open AccessCommunication

Extraction of pH-Dependent DNA-Binding Anti-Tumoral Peptides from Saccharomyces cerevisiae

by Francesco Ragonese and Loretta Mancinelli

Pharmaceuticals 2026, 19(1), 184; https://doi.org/10.3390/ph19010184 - 21 Jan 2026

Viewed by 483

Abstract

Cancer remains a significant challenge in the field of medicine, primarily due to its inherent plasticity and the development of resistance to conventional therapeutic interventions. Genomic mutations and the activation of oncogenes enable cancer cells to resist senescence and apoptosis, leading to uncontrolled [...] Read more.

Cancer remains a significant challenge in the field of medicine, primarily due to its inherent plasticity and the development of resistance to conventional therapeutic interventions. Genomic mutations and the activation of oncogenes enable cancer cells to resist senescence and apoptosis, leading to uncontrolled growth with harmful consequences. Small peptides are molecules with interesting anti-tumour properties and represent a valid alternative to conventional treatments. Our group has previously identified a class of small peptides bound to the DNA that can be extracted from the chromatin of various tissues, including wheat germ and trout. These peptide pools have been shown to possess interesting antiproliferative and apoptotic properties, and they are associated with cell cycle regulation. However, given the complexity of the extraction process, it is necessary to identify a substrate that will enable a more efficient extraction of these peptides, while also ensuring a composition that is simple to investigate. The present study developed a method for the extraction of this group of peptides from yeast, and the extract was then tested on cancer cells in order to confirm its anti-tumoral properties. The peptides were obtained from chromatin extracted from Saccharomyces cerevisiae cells through alkalisation and purification by gel filtration chromatography. The extract was tested on HeLa cells to verify its effects on vitality and the cell cycle. The data demonstrate that the chromatographic profile of this peptide extract indicates a more basic composition than the pool extracted from other tissues and exhibits comparable antiproliferative properties. The ability to rapidly obtain a biologically active, analytically accessible, and adequately purified fraction from the widely available substrate Saccharomyces cerevisiae represents a significant advance in the study of these DNA-binding peptides. Full article

(This article belongs to the Topic Peptoids and Peptide Based Drugs)

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13 pages, 2858 KB  

Open AccessArticle

Dose-Dependent Cellular Phenotypic Change Induced by ¹⁷⁷Lu-Oxodotreotide Treatment in IMR-32 Cells

by Shuai Xue, Xiaobei Zheng, Bingbing Pu, Xiao Li, Jun Li, Meng Huang, Jian Yang and Jingjing Lou

Biomedicines 2025, 13(7), 1543; https://doi.org/10.3390/biomedicines13071543 - 25 Jun 2025

Viewed by 1163

Abstract

Objectives: Beta-emitting radionuclide therapy, exemplified by ¹⁷⁷Lu-Oxodotreotide (Lutathera^®), enables targeted treatment of neuroendocrine tumors by delivering β-radiation to tumor cells. However, the dose-dependent molecular mechanisms underlying cellular damage remain insufficiently characterized. This study aimed to investigate the phenotypic changes [...] Read more.

Objectives: Beta-emitting radionuclide therapy, exemplified by ¹⁷⁷Lu-Oxodotreotide (Lutathera^®), enables targeted treatment of neuroendocrine tumors by delivering β-radiation to tumor cells. However, the dose-dependent molecular mechanisms underlying cellular damage remain insufficiently characterized. This study aimed to investigate the phenotypic changes in IMR-32 human neuroblastoma cells following Lutathera exposure, with a focus on the dose-dependent relationship between radiation and cellular damage. Methods: IMR-32 cells were allocated to control, low- (0.05 MBq/mL), medium- (0.5 MBq/mL), and high-dose (5 MBq/mL) groups and treated with ¹⁷⁷Lu-Oxodotreotide for 24 h. Flow cytometry was employed to assess cell viability, apoptosis, mitochondrial membrane potential, γ-H2AX expression (a marker of DNA damage), and proliferation. Results: Lutathera induced dose-dependent cytotoxic effects. Cell viability declined linearly with increasing dose (control: 100% vs. high-dose: 13.48%; r = −0.955, p < 0.001). Apoptosis was significantly elevated (control: 35.34% vs. high-dose: 88.12%; r = 0.999), accompanied by increased γ-H2AX levels (control: 5.26 × 10⁴ vs. high-dose: 13.13 × 10⁴; r = 0.930), indicating DNA double-strand breaks. Mitochondrial membrane potential decreased (control: 6.06 × 10⁴ vs. high-dose: 46.27 × 10⁴; r = 0.999), and proliferation was suppressed (control: 91.10 × 10⁴ vs. high-dose: 103.84 × 10⁴; r = 0.954), both showing strong dose correlations (p < 0.001). Conclusions: ¹⁷⁷Lu-Oxodotreotide exerts dose-dependent cytotoxicity in IMR-32 cells via DNA damage, mitochondrial dysfunction, and apoptosis induction. These findings underscore the necessity of optimizing dosing regimens to balance therapeutic efficacy and safety in clinical settings, providing a foundation for personalized β-emitter therapies. Full article

(This article belongs to the Topic Peptoids and Peptide Based Drugs)

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16 pages, 1196 KB  

Open AccessReview

Peptide with Dual Roles in Immune and Metabolic Regulation: Liver-Expressed Antimicrobial Peptide-2 (LEAP-2)

by Yitong Li, Ying Liu and Meng Gou

Molecules 2025, 30(2), 429; https://doi.org/10.3390/molecules30020429 - 20 Jan 2025

Cited by 8 | Viewed by 4025

Abstract

Liver-expressed antimicrobial peptide 2 (LEAP-2) was originally discovered as an antimicrobial peptide that plays a vital role in the host innate immune system of various vertebrates. Recent research discovered LEAP-2 as an endogenous antagonist and inverse agonist of the GHSR1a receptor. By acting [...] Read more.

Liver-expressed antimicrobial peptide 2 (LEAP-2) was originally discovered as an antimicrobial peptide that plays a vital role in the host innate immune system of various vertebrates. Recent research discovered LEAP-2 as an endogenous antagonist and inverse agonist of the GHSR1a receptor. By acting as a competitive antagonist to ghrelin, LEAP-2 influences energy balance and metabolic processes via the ghrelin–GHSR1a signaling pathway. LEAP-2 alone or the LEAP-2/ghrelin molar ratio showed potential as therapeutic targets for obesity, diabetes, and metabolic disorders. This review explores the recent advances of LEAP-2 in immune modulation and energy regulation, highlighting its potential in treating the above diseases. Full article

(This article belongs to the Topic Peptoids and Peptide Based Drugs)

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37 pages, 67526 KB  

Open AccessArticle

Stable Gastric Pentadecapeptide BPC 157 as Therapy After Surgical Detachment of the Quadriceps Muscle from Its Attachments for Muscle-to-Bone Reattachment in Rats

by Danijel Matek, Irena Matek, Eva Staresinic, Mladen Japjec, Ivan Bojanic, Alenka Boban Blagaic, Lidija Beketic Oreskovic, Ivana Oreskovic, Tihomil Ziger, Tomislav Novinscak, Ivan Krezic, Sanja Strbe, Martin Drinkovic, Filip Brkic, Jelena Popic, Anita Skrtic, Sven Seiwerth, Mario Staresinic, Predrag Sikiric and Ivica Brizic

Pharmaceutics 2025, 17(1), 119; https://doi.org/10.3390/pharmaceutics17010119 - 16 Jan 2025

Cited by 6 | Viewed by 13172

Abstract

Background: This is a novel rat study using native peptide therapy, focused on reversing quadriceps muscle-to-bone detachment to reattachment and stable gastric pentadecapeptide BPC 157 per-oral therapy for shared muscle healing and function restoration. Methods: Pharmacotherapy recovering various muscle, tendon, ligament, and bone [...] Read more.

Background: This is a novel rat study using native peptide therapy, focused on reversing quadriceps muscle-to-bone detachment to reattachment and stable gastric pentadecapeptide BPC 157 per-oral therapy for shared muscle healing and function restoration. Methods: Pharmacotherapy recovering various muscle, tendon, ligament, and bone lesions, and severed junctions (i.e., myotendinous junction), per-oral in particular (BPC 157/kg/day 10 µg, 10 ng), provides muscle-to-bone reattachment after quadriceps muscle detachment, both complete (rectus muscle) and partial (vastus muscles). Results: Immediately post-injury, and at 1, 2, 3, 5, 7, 14, 21, 28, 60, and 90 days post-injury, quadriceps muscle-to-bone detachment showed definitive healing failure (impaired walking and permanent knee flexure). Contrarily, macro/microscopic, ultrasonic, magnetic resonance, biomechanical, and functional assessments revealed that BPC 157 therapy recovering effects for all time points were consistent. All parameters of the walking pattern fully improved, and soon after detachment and therapy application, muscle approached the bone, leaving a minimal gap (on ultrasonic assessment), and leg contracture was annihilated. The healing process occurs immediately after detachment from both sides: the muscle and the bone. The reattachment fibers from the ends of the muscle could be traced into the new bone formed at the surface (note, at day 3 post-detachment, increased mesenchymal cells occurred with periosteum reactivation). Consequently, at 3 months, the form was stable, and the balance between the muscle and bone was the following: well-organized bone, newly formed as more cortical bone providing a narrower bone marrow space, and the muscle and mature fibers were oriented parallel to the bone axis and were in close contact with bone. Conclusions: Therefore, to achieve quadriceps muscle-to-bone reattachment, the BPC 157 therapy reversing course acts from the beginning, resolving an otherwise insurmountable deleterious course. Full article

(This article belongs to the Topic Peptoids and Peptide Based Drugs)

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17 pages, 1650 KB  

Open AccessReview

Marine Peptides: Potential Basic Structures for the Development of Hybrid Compounds as Multitarget Therapeutics for the Treatment of Multifactorial Diseases

by Marta Bauer, Magdalena Glowacka, Wojciech Kamysz and Patrycja Kleczkowska

Int. J. Mol. Sci. 2024, 25(23), 12601; https://doi.org/10.3390/ijms252312601 - 23 Nov 2024

Cited by 7 | Viewed by 3392

Abstract

Marine-derived peptides display potent antihypertensive, antioxidant, analgesic and antimicrobial biological effects. Some of them have also been found to have anticancer activity via various mechanisms differing from those of continental organisms. This diversity of properties—together with the peptides’ efficacy, which has been confirmed [...] Read more.

Marine-derived peptides display potent antihypertensive, antioxidant, analgesic and antimicrobial biological effects. Some of them have also been found to have anticancer activity via various mechanisms differing from those of continental organisms. This diversity of properties—together with the peptides’ efficacy, which has been confirmed in several in vitro and in vivo studies—make these compounds attractive as functional ingredients in pharmacy, especially in regard to multitarget drugs known as hybrids. Given the possibilities offered by chimeric structures, it is expected that a hybridization strategy based on a marine-derived compound could result in a long-awaited success in the development of new effective compounds to combat a range of complex diseases. However, despite the fact that the biological activity of such new hybrids may exceed that of their parent compounds, there is still an urgent need to carefully determine their potential off-targets and thus possible clinically important side effects. Given the above, the aim of this paper is to provide information on compounds of marine origin with peptide structures and to verify the occurrence and usage of hybrid compounds built from these structures. Furthermore, the authors believe that information presented here will serve to increase public awareness of the new opportunities arising from the combination of hybridization strategies with marine molecules with known structures and biological properties, thereby accelerating the development of effective drug candidates. Full article

(This article belongs to the Topic Peptoids and Peptide Based Drugs)

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13 pages, 3205 KB  

Open AccessArticle

From In Vitro Promise to In Vivo Reality: An Instructive Account of Infection Model Evaluation of Antimicrobial Peptides

by Adam Carrera-Aubesart, Jiarui Li, Estefanía Contreras, Roberto Bello-Madruga, Marc Torrent and David Andreu

Int. J. Mol. Sci. 2024, 25(18), 9773; https://doi.org/10.3390/ijms25189773 - 10 Sep 2024

Cited by 2 | Viewed by 2614

Abstract

Antimicrobial peptides (AMPs) are regarded as a promising alternative to traditional antibiotics in the face of ever-increasing resistance. However, many AMPs fail to progress into clinics due to unexpected difficulties found in preclinical in vivo phases. Our research has focused on crotalicidin (Ctn), [...] Read more.

Antimicrobial peptides (AMPs) are regarded as a promising alternative to traditional antibiotics in the face of ever-increasing resistance. However, many AMPs fail to progress into clinics due to unexpected difficulties found in preclinical in vivo phases. Our research has focused on crotalicidin (Ctn), an AMP from snake venom, and a fragment thereof, Ctn[15-34], with improved in vitro antimicrobial and anticancer activities and remarkable serum stability. As the retroenantio versions of both AMPs maintained favorable profiles, in this work, we evaluate the in vivo efficacy of both the native-sequence AMPs and their retroenantio counterparts in a murine infection model with Acinetobacter baumannii. A significant reduction in bacterial levels is found in the mice treated with Ctn[15-34]. However, contrary to expectations, the retroenantio analogs either exhibit toxicity or lack efficacy when administered to mice. Our findings underscore the critical importance of in vivo infection model evaluation to fully calibrate the therapeutic potential of AMPs. Full article

(This article belongs to the Topic Peptoids and Peptide Based Drugs)

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17 pages, 3486 KB  

Open AccessArticle

Opioid/Dopamine Receptor Binding Studies, NMR and Molecular Dynamics Simulation of LENART01 Chimera, an Opioid-Bombesin-like Peptide

by Pawel Serafin, Łukasz Szeleszczuk, Igor Zhukov, Edina Szűcs, Dávid Gombos, Azzurra Stefanucci, Adriano Mollica, Dariusz Maciej Pisklak and Patrycja Kleczkowska

Molecules 2024, 29(1), 272; https://doi.org/10.3390/molecules29010272 - 4 Jan 2024

Cited by 6 | Viewed by 4001

Abstract

The design and development of hybrid compounds as a new class of drug candidates remains an excellent opportunity to improve the pharmacological properties of drugs (including enzymatic stability, efficacy and pharmacokinetic and pharmacodynamic profiles). In addition, considering various complex diseases and/or disorders, the [...] Read more.

The design and development of hybrid compounds as a new class of drug candidates remains an excellent opportunity to improve the pharmacological properties of drugs (including enzymatic stability, efficacy and pharmacokinetic and pharmacodynamic profiles). In addition, considering various complex diseases and/or disorders, the conjugate chemistry approach is highly acceptable and justified. Opioids have long been recognized as the most potent analgesics and serve as the basic pharmacophore for potent hybrid compounds that may be useful in pain management. However, a risk of tolerance and physical dependence exists. Since dopamine receptors have been implicated in the aforementioned adverse effects of opioids, the construction of a hybrid with dual action at opioid and dopamine receptors is of interest. Herein, we present nuclear magnetic resonance (NMR) spectroscopy and molecular dynamics simulation results for LENART01, an opioid–ranatensin hybrid peptide. Apart from molecular docking, protein–ligand interactions were also assessed in vitro using a receptor binding assay, which proved LENART01 to be bound to mu-opioid and dopamine receptors, respectively. Full article

(This article belongs to the Topic Peptoids and Peptide Based Drugs)

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15 pages, 1908 KB  

Open AccessReview

Peptoids: Smart and Emerging Candidates for the Diagnosis of Cancer, Neurological and Autoimmune Disorders

by Anna Giorgio, Annarita Del Gatto, Simone Pennacchio, Michele Saviano and Laura Zaccaro

Int. J. Mol. Sci. 2023, 24(22), 16333; https://doi.org/10.3390/ijms242216333 - 15 Nov 2023

Cited by 8 | Viewed by 3061

Abstract

Early detection of fatal and disabling diseases such as cancer, neurological and autoimmune dysfunctions is still desirable yet challenging to improve quality of life and longevity. Peptoids (N-substituted glycine oligomers) are a relatively new class of peptidomimetics, being highly versatile and capable of [...] Read more.

Early detection of fatal and disabling diseases such as cancer, neurological and autoimmune dysfunctions is still desirable yet challenging to improve quality of life and longevity. Peptoids (N-substituted glycine oligomers) are a relatively new class of peptidomimetics, being highly versatile and capable of mimicking the architectures and the activities of the peptides but with a marked resistance to proteases and a propensity to cross the cellular membranes over the peptides themselves. For these properties, they have gained an ever greater interest in applications in bioengineering and biomedical fields. In particular, the present manuscript is to our knowledge the only review focused on peptoids for diagnostic applications and covers the last decade’s literature regarding peptoids as tools for early diagnosis of pathologies with a great impact on human health and social behavior. The review indeed provides insights into the peptoid employment in targeted cancer imaging and blood-based screening of neurological and autoimmune diseases, and it aims to attract the scientific community’s attention to continuing and sustaining the investigation of these peptidomimetics in the diagnosis field considering their promising peculiarities. Full article

(This article belongs to the Topic Peptoids and Peptide Based Drugs)

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18 pages, 2712 KB  

Open AccessReview

Bombesins: A New Frontier in Hybrid Compound Development

by Pawel Serafin and Patrycja Kleczkowska

Pharmaceutics 2023, 15(11), 2597; https://doi.org/10.3390/pharmaceutics15112597 - 7 Nov 2023

Cited by 5 | Viewed by 3326

Abstract

Recently, bombesin (BN) and its analogs have attracted much attention as excellent anticancer agents because they interact with specific receptors widely distributed on the surface of various cancer cells. However, their biological properties proceed far beyond this, given a broad spectrum of activity. [...] Read more.

Recently, bombesin (BN) and its analogs have attracted much attention as excellent anticancer agents because they interact with specific receptors widely distributed on the surface of various cancer cells. However, their biological properties proceed far beyond this, given a broad spectrum of activity. Bombesin receptor ligands are effective drugs for the treatment of rheumatoid arthritis or gastrointestinal diseases. However, most diseases are complex, and the use of polytherapy may lead to pharmacokinetic and pharmacodynamic drug–drug interactions, resulting in side effects. Therefore, there is a need to develop effective compounds that also contain BN or its analogs, which are combined with other structural entities, thus generating a so-called hybrid drug. Hybrid drugs that contain bombesin pharmacophore(s) may be proposed as a solution to the problem of polytherapy or the lack of an effective cure. Such structures have now demonstrated the desired efficacy, though information on these aforementioned compounds is relatively scarce. Therefore, our paper aims to encourage researchers to focus on bombesins. Herein, we indicate that the hybrid approach should also be firmly applied to bombesins and the BN receptor family. This paper’s structure is divided into two main sections demonstrating bombesins and their properties, as well as recent data on bombesin-based hybrid compounds and their potential usefulness in medicine. Overall, it refers to the discovery and synthesis of modified bombesin-based hybrid compounds. Full article

(This article belongs to the Topic Peptoids and Peptide Based Drugs)

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17 pages, 3574 KB  

Open AccessArticle

The Synthetic Peptide GA-Hecate and Its Analogs Inhibit Multiple Steps of the Chikungunya Virus Infection Cycle In Vitro

by Gabriela Miranda Ayusso, Paulo Ricardo da Silva Sanches, Tamara Carvalho, Igor Andrade Santos, Daniel Oliveira Silva Martins, Maria Letícia Duarte Lima, Pâmela Jóyce Previdelli da Conceição, Cíntia Bittar, Andres Merits, Eduardo Maffud Cilli, Ana Carolina Gomes Jardim, Paula Rahal and Marilia Freitas Calmon

Pharmaceuticals 2023, 16(10), 1389; https://doi.org/10.3390/ph16101389 - 30 Sep 2023

Cited by 9 | Viewed by 2838

Abstract

Chikungunya virus (CHIKV) belongs to the Alphavirus genus and is responsible for significant outbreaks worldwide. Currently, there is no approved antiviral therapy against CHIKV. Bioactive peptides have great potential for new drug development. Here, we evaluated the antiviral activity of the synthetic peptide [...] Read more.

Chikungunya virus (CHIKV) belongs to the Alphavirus genus and is responsible for significant outbreaks worldwide. Currently, there is no approved antiviral therapy against CHIKV. Bioactive peptides have great potential for new drug development. Here, we evaluated the antiviral activity of the synthetic peptide GA-Hecate and its analogs PSSct1905 and PSSct1910 against CHIKV infection. Initial screening showed that all three peptides inhibited the CHIKV replication cycle in baby hamster kidney fibroblast cells (BHK-21) and human hepatocarcinoma epithelial cells (Huh-7). GA-Hecate and its analog PSSct1905 were the most active, demonstrating suppression of viral infection by more than 91%. The analog PSSct1905 exhibited a protective effect in cells against CHIKV infection. We also observed that the analogs PSSct1905 and PSSct1910 affected CHIKV entry into both cell lines, inhibiting viral attachment and internalization. Finally, all tested compounds presented antiviral activity on the post-entry steps of CHIKV infection in all cells evaluated. In conclusion, this study highlights the potential of the peptide GA-Hecate and its analogs as novel anti-CHIKV compounds targeting different stages of the viral replication cycle, warranting the development of GA-Hecate-based compounds with broad antiviral activity. Full article

(This article belongs to the Topic Peptoids and Peptide Based Drugs)

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32 pages, 2470 KB  

Open AccessReview

Peptide Vaccines as Therapeutic and Prophylactic Agents for Female-Specific Cancers: The Current Landscape

by Manju Lekshmy, Chandrasekharan Rajalekshmi Dhanya, Jayashree SatheeshKumar Smrithi, Janaki Anandavallyamma Sindhurani, Jiji Joseph Vandanamthadathil, Jayakrishnan Therthala Veettil, Leelamma Anila, Vishnu Sasidharan Lathakumari, Adhira M. Nayar and Maya Madhavan

Pharmaceuticals 2023, 16(7), 1054; https://doi.org/10.3390/ph16071054 - 24 Jul 2023

Cited by 7 | Viewed by 9263

Abstract

Breast and gynecologic cancers are significant global threats to women’s health and those living with the disease require lifelong physical, financial, and social support from their families, healthcare providers, and society as a whole. Cancer vaccines offer a promising means of inducing long-lasting [...] Read more.

Breast and gynecologic cancers are significant global threats to women’s health and those living with the disease require lifelong physical, financial, and social support from their families, healthcare providers, and society as a whole. Cancer vaccines offer a promising means of inducing long-lasting immune response against the disease. Among various types of cancer vaccines available, peptide vaccines offer an effective strategy to elicit specific anti-tumor immune responses. Peptide vaccines have been developed based on tumor associated antigens (TAAs) and tumor specific neoantigens which can also be of viral origin. Molecular alterations in HER2 and non-HER2 genes are established to be involved in the pathogenesis of female-specific cancers and hence were exploited for the development of peptide vaccines against these diseases, most of which are in the latter stages of clinical trials. However, prophylactic vaccines for viral induced cancers, especially those against Human Papillomavirus (HPV) infection are well established. This review discusses therapeutic and prophylactic approaches for various types of female-specific cancers such as breast cancer and gynecologic cancers with special emphasis on peptide vaccines. We also present a pipeline for the design and evaluation of a multiepitope peptide vaccine that can be active against female-specific cancers. Full article

(This article belongs to the Topic Peptoids and Peptide Based Drugs)

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25 pages, 6578 KB  

Open AccessReview

Review: Structure-Activity Relationship of Antimicrobial Peptoids

by Priscilla L. Nyembe, Thandokuhle Ntombela and Maya M. Makatini

Pharmaceutics 2023, 15(5), 1506; https://doi.org/10.3390/pharmaceutics15051506 - 15 May 2023

Cited by 34 | Viewed by 5513

Abstract

Due to their broad-spectrum activity against Gram-negative and Gram-positive bacteria, natural antimicrobial peptides (AMPs) and their synthetic analogs have emerged as prospective therapies for treating illnesses brought on by multi-drug resistant pathogens. To overcome the limitations of AMPs, such as protease degradation, oligo-N-substituted [...] Read more.

Due to their broad-spectrum activity against Gram-negative and Gram-positive bacteria, natural antimicrobial peptides (AMPs) and their synthetic analogs have emerged as prospective therapies for treating illnesses brought on by multi-drug resistant pathogens. To overcome the limitations of AMPs, such as protease degradation, oligo-N-substituted glycines (peptoids) are a promising alternative. Despite having the same backbone atom sequence as natural peptides, peptoid structures are more stable because, unlike AMP, their functional side chains are attached to the backbone nitrogen (N)-atom rather than the alpha carbon atom. As a result, peptoid structures are less susceptible to proteolysis and enzymatic degradation. The advantages of AMPs, such as hydrophobicity, cationic character, and amphipathicity, are mimicked by peptoids. Furthermore, structure-activity relationship studies (SAR) have shown that tuning the structure of peptoids is a crucial step in developing effective antimicrobials. Full article

(This article belongs to the Topic Peptoids and Peptide Based Drugs)

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24 pages, 1597 KB  

Open AccessReview

Designing Formulation Strategies for Enhanced Stability of Therapeutic Peptides in Aqueous Solutions: A Review

by Primawan Putra Nugrahadi, Wouter L. J. Hinrichs, Henderik W. Frijlink, Christian Schöneich and Christina Avanti

Pharmaceutics 2023, 15(3), 935; https://doi.org/10.3390/pharmaceutics15030935 - 14 Mar 2023

Cited by 66 | Viewed by 17431

Abstract

Over the past few decades, there has been a tremendous increase in the utilization of therapeutic peptides. Therapeutic peptides are usually administered via the parenteral route, requiring an aqueous formulation. Unfortunately, peptides are often unstable in aqueous solutions, affecting stability and bioactivity. Although [...] Read more.

Over the past few decades, there has been a tremendous increase in the utilization of therapeutic peptides. Therapeutic peptides are usually administered via the parenteral route, requiring an aqueous formulation. Unfortunately, peptides are often unstable in aqueous solutions, affecting stability and bioactivity. Although a stable and dry formulation for reconstitution might be designed, from a pharmaco-economic and practical convenience point of view, a peptide formulation in an aqueous liquid form is preferred. Designing formulation strategies that optimize peptide stability may improve bioavailability and increase therapeutic efficacy. This literature review provides an overview of various degradation pathways and formulation strategies to stabilize therapeutic peptides in aqueous solutions. First, we introduce the major peptide stability issues in liquid formulations and the degradation mechanisms. Then, we present a variety of known strategies to inhibit or slow down peptide degradation. Overall, the most practical approaches to peptide stabilization are pH optimization and selecting the appropriate type of buffer. Other practical strategies to reduce peptide degradation rates in solution are the application of co-solvency, air exclusion, viscosity enhancement, PEGylation, and using polyol excipients. Full article

(This article belongs to the Topic Peptoids and Peptide Based Drugs)

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