Synthesis and Applications of Peptides and Peptidomimetics in Drug Discovery

JIMMIDI, RAVIKUMAR

doi:10.1002/ejoc.202300028

Cited by 8 publications

(5 citation statements)

References 170 publications

(283 reference statements)

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“…Since proteases cleave peptide bonds, most researched protease inhibitors are peptide-based molecules, which include the use of naturally occurring amino acids, or peptidomimetics, which contain modified amino acids with enhanced molecular properties that increase their affinity towards the active site, while also improving their pharmacological properties by enhancing stability [ 22 ]. According to El-Faham et al [ 23 ], peptide-based molecules account for 5% of the total number of drugs approved by the FDA between January 2015 and May 2021, with 21 drugs being launched during the same period for many targets.…”

Section: Inhibition Of Viral Proteases By Targeting the Active Sitementioning

confidence: 99%

Recent Advances on Targeting Proteases for Antiviral Development

Borges,

Ferreira,

Silva

2024

Viruses

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Viral proteases are an important target for drug development, since they can modulate vital pathways in viral replication, maturation, assembly and cell entry. With the (re)appearance of several new viruses responsible for causing diseases in humans, like the West Nile virus (WNV) and the recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), understanding the mechanisms behind blocking viral protease’s function is pivotal for the development of new antiviral drugs and therapeutical strategies. Apart from directly inhibiting the target protease, usually by targeting its active site, several new pathways have been explored to impair its activity, such as inducing protein aggregation, targeting allosteric sites or by inducing protein degradation by cellular proteasomes, which can be extremely valuable when considering the emerging drug-resistant strains. In this review, we aim to discuss the recent advances on a broad range of viral proteases inhibitors, therapies and molecular approaches for protein inactivation or degradation, giving an insight on different possible strategies against this important class of antiviral target.

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Section: Inhibition Of Viral Proteases By Targeting the Active Sitementioning

confidence: 99%

Recent Advances on Targeting Proteases for Antiviral Development

Borges,

Ferreira,

Silva

2024

Viruses

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“…Each group of rats received ACTY116 pLAI formulated with a different PLGA type at a single SC dose of 14 mg/kg. The blood samples were collected from the retrobulbar venous plexus at hours 1, 2, and 4 and on days 1, 3,5,7,9,11,13,15,17,19,21,23,25,27,29,31,33, and 35 post subcutaneous injection; then, plasma was separated by refrigerated centrifuge, and ACTY116 was analysed with a LC-MS/MS method.…”

Section: In Vitro Release Testing For Acty116 Pgla In Situ Depot Gel ...mentioning

confidence: 99%

“…Moreover, rapid renal clearance and enzymatic degradation lead to short half-lives, requiring frequent administration and incurring compliance and cost issues. Peptides also face chemical and conformational instability, compromising their efficacy and safety [3,4]. Formulating stable and long-acting peptide dosage forms is a complex task.…”

Section: Introductionmentioning

confidence: 99%

Development and Evaluation of a Water-Free In Situ Depot Gel Formulation for Long-Acting and Stable Delivery of Peptide Drug ACTY116

Xiong,

Liu,

Wang

et al. 2024

Pharmaceutics

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In situ depot gel is a type of polymeric long-acting injectable (pLAI) drug delivery system; compared to microsphere technology, its preparation process is simpler and more conducive to industrialization. To ensure the chemical stability of peptide ACTY116, we avoided the use of harsh conditions such as high temperatures, high shear mixing, or homogenization; maintaining a water-free and oxygen-free environment was also critical to prevent hydrolysis and oxidation. Molecular dynamics (MDs) simulations were employed to assess the stability mechanism between ACTY116 and the pLAI system. The initial structure of ACTY116 with an alpha helix conformation was constructed using SYBYL-X, and the copolymer PLGA was generated by AMBER 16; results showed that PLGA-based in situ depot gel improved conformational stability of ACTY116 through hydrogen bonds formed between peptide ACTY116 and the components of the pLAI formulation, while PLGA (Poly(DL-lactide-co-glycolide)) also created steric hindrance and shielding effects to prevent conformational changes. As a result, the chemical and conformational stability and in vivo long-acting characteristics of ACTY116 ensure its enhanced efficacy. In summary, we successfully achieved our objective of developing a highly stable peptide-loaded long-acting injectable (LAI) in situ depot gel formulation that is stable for at least 3 months under harsh conditions (40 °C, above body temperature), elucidating the underlying stabilisation mechanism, and the high stability of the ACTY116 pLAI formulation creates favourable conditions for its in vivo pharmacological activity lasting for weeks or even months.

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“…Peptides are short chains with less than 50 amino acids connected by peptide bonds, encompassing a wide variety of types and mostly exhibiting favorable biological activity [144]. Among them, RGD peptide (Arg-Gly-Asp) has been extensively studied.…”

Section: Peptidesmentioning

confidence: 99%

Progress of research on the surface functionalization of tantalum and porous tantalum in bone tissue engineering

Li,

Zhu,

Che

et al. 2024

Biomed. Mater.

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Tantalum and porous tantalum are ideal materials for making orthopedic implants due to their stable chemical properties and excellent biocompatibility. However, their utilization is still affected by loosening, infection, and peripheral inflammatory reactions, which sometimes ultimately lead to implant removal. An ideal bone implant should have exceptional biological activity, which can improve the surrounding biological microenvironment to enhance bone repair. Recent advances in surface functionalization have produced various strategies for developing compatibility between either of the two materials and their respective microenvironments. This review provides a systematic overview of state-of-the-art strategies for conferring biological functions to tantalum and porous tantalum implants. Furthermore, the review describes methods for preparing active surfaces and different bioactive substances that are used, summarizing their functions. Finally, this review discusses current challenges in the development of optimal bone implant materials.

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Synthesis and Applications of Peptides and Peptidomimetics in Drug Discovery

Cited by 8 publications

References 170 publications

Recent Advances on Targeting Proteases for Antiviral Development

Recent Advances on Targeting Proteases for Antiviral Development

Development and Evaluation of a Water-Free In Situ Depot Gel Formulation for Long-Acting and Stable Delivery of Peptide Drug ACTY116

Progress of research on the surface functionalization of tantalum and porous tantalum in bone tissue engineering

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