Lung cancer (LC) is the leading cause of cancer-related death globally. Comprehensive knowledge of the cellular and molecular etiology of LC is perilous for the development of active treatment approaches. Hypoxia in cancer is linked with malignancy, and its phenotype is implicated in the hypoxic reaction, which is being studied as a prospective cancer treatment target. The hypervascularization of the tumor is the main feature of human LC, and hypoxia is a major stimulator of neo-angiogenesis. It was seen that low oxygen levels in human LC are a critical aspect of this lethal illness. However, as there is a considerable body of literature espousing the presumed functional relevance of hypoxia in LC, the direct measurement of oxygen concentration in Human LC is yet to be determined. This narrative review aims to show the importance and as a future target for novel research studies that can lead to the perception of LC therapy in hypoxic malignancies.
{"title":"Hypoxia A Typical Target in Human Lung Cancer Therapy.","authors":"Asmat Ullah, Somia Shehzadi, Najeeb Ullah, Touseef Nawaz, Haroon Iqbal, Tariq Aziz","doi":"10.2174/0113892037252820231114045234","DOIUrl":"10.2174/0113892037252820231114045234","url":null,"abstract":"<p><p>Lung cancer (LC) is the leading cause of cancer-related death globally. Comprehensive knowledge of the cellular and molecular etiology of LC is perilous for the development of active treatment approaches. Hypoxia in cancer is linked with malignancy, and its phenotype is implicated in the hypoxic reaction, which is being studied as a prospective cancer treatment target. The hypervascularization of the tumor is the main feature of human LC, and hypoxia is a major stimulator of neo-angiogenesis. It was seen that low oxygen levels in human LC are a critical aspect of this lethal illness. However, as there is a considerable body of literature espousing the presumed functional relevance of hypoxia in LC, the direct measurement of oxygen concentration in Human LC is yet to be determined. This narrative review aims to show the importance and as a future target for novel research studies that can lead to the perception of LC therapy in hypoxic malignancies.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138458461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/0113892037264538231128072614
Muhammad Haris Ramzan, Mohsin Shah, Faiqah Ramzan
Background: Neurokinin B; an endogenous decapeptide, mediates its reproductive physiological actions through gonadotropin releasing hormone. Despite the potential role of Neurokinin B on seminal vesicles, its effects on seminal vesicles in adult male mammals remain elusive. We aimed to investigate the potentials of variable doses of Neurokinin B, its agonist and antagonist on histomorphology and expression of NK3R on seminal vesicles, and secretory activity of seminal vesicles in adult male rats.
Methods: Adult male Sprague Dawley rats (n=10 in each group) were administered intraperitoneally with Neurokinin B in three variable doses: 1 μg, 1 ηg and 10 ρg while, Senktide (Neurokinin B agonist) and SB222200 (Neurokinin B antagonist) in 1 μg doses consecutively for 12 days. After 12 days of peptide treatment, half of the animals (n=05) in each group were sacrificed while remaining half (n=05) were kept for another 12 days without any treatment to investigate treatment reversal. Seminal vesicles were dissected and excised tissue was processed for light microscopy, immunohistochemistry and estimation of seminal fructose levels.
Results: Treatment with Neurokinin B and Senktide significantly increased while SB222200 slightly decrease the seminal vesicles weight, epithelial height and seminal fructose levels as compared to control. Light microscopy revealed increased epithelial height and epithelial folding as compared to control in all Neurokinin B and Senktide treated groups while decreased in SB222200. Effects of various doses of Neurokinin B, Senktide and SB222200 on seminal vesicles weight, epithelial height, seminal fructose levels and histomorphology were reversed when rats were maintained without treatments. Immuno-expression of Neurokinin B shows no change in treatment and reversal groups.
Conclusion: Continuous administration of Neurokinin B and Senktide effect positively while SB222200 have detrimental effects on cellular morphology, epithelial height and seminal fructose levels in seminal vesicles. Effects of peptide treatments depicted a reversal towards control group when rats were kept without any treatment.
背景:神经激肽 B 是一种内源性十肽,通过促性腺激素释放激素介导其生殖生理作用。尽管神经激肽B对精囊具有潜在作用,但其对成年雄性哺乳动物精囊的影响仍然难以捉摸。我们旨在研究不同剂量的神经激肽B、其激动剂和拮抗剂对成年雄性大鼠精囊组织形态学、精囊上NK3R的表达以及精囊分泌活性的潜在影响:成年雄性 Sprague Dawley 大鼠(每组 10 只)腹腔注射三种不同剂量的神经激肽 B:1 μg、1 ηg和10 μg,同时连续注射1 μg剂量的Senktide(神经激肽B激动剂)和SB222200(神经激肽B拮抗剂)12天。多肽治疗 12 天后,每组一半动物(n=05)被处死,另一半动物(n=05)在没有任何治疗的情况下再保留 12 天,以研究治疗逆转。解剖精囊并对切除的组织进行光镜观察、免疫组化和精液果糖水平评估:结果:与对照组相比,神经激肽B和Senktide能明显增加精囊重量、上皮高度和精液果糖水平,而SB222200能略微降低精囊重量、上皮高度和精液果糖水平。光镜观察显示,与对照组相比,所有神经激肽 B 和参肽处理组的上皮高度和上皮褶皱均有所增加,而 SB222200 处理组则有所减少。不同剂量的神经激肽 B、Senktide 和 SB222200 对精囊重量、上皮高度、精液果糖水平和组织形态学的影响在大鼠未接受治疗的情况下被逆转。神经激肽 B 的免疫表达在治疗组和逆转组均无变化:连续给药神经激肽 B 和 SB222200 会对精囊细胞形态、上皮高度和精液果糖水平产生积极影响,而 SB222200 则会产生有害影响。当大鼠未接受任何治疗时,肽治疗的效果会向对照组逆转。
{"title":"Neurokinin B Administration Induces Dose Dependent Proliferation of Seminal Vesicles in Adult Rats.","authors":"Muhammad Haris Ramzan, Mohsin Shah, Faiqah Ramzan","doi":"10.2174/0113892037264538231128072614","DOIUrl":"10.2174/0113892037264538231128072614","url":null,"abstract":"<p><strong>Background: </strong>Neurokinin B; an endogenous decapeptide, mediates its reproductive physiological actions through gonadotropin releasing hormone. Despite the potential role of Neurokinin B on seminal vesicles, its effects on seminal vesicles in adult male mammals remain elusive. We aimed to investigate the potentials of variable doses of Neurokinin B, its agonist and antagonist on histomorphology and expression of NK3R on seminal vesicles, and secretory activity of seminal vesicles in adult male rats.</p><p><strong>Methods: </strong>Adult male Sprague Dawley rats (n=10 in each group) were administered intraperitoneally with Neurokinin B in three variable doses: 1 μg, 1 ηg and 10 ρg while, Senktide (Neurokinin B agonist) and SB222200 (Neurokinin B antagonist) in 1 μg doses consecutively for 12 days. After 12 days of peptide treatment, half of the animals (n=05) in each group were sacrificed while remaining half (n=05) were kept for another 12 days without any treatment to investigate treatment reversal. Seminal vesicles were dissected and excised tissue was processed for light microscopy, immunohistochemistry and estimation of seminal fructose levels.</p><p><strong>Results: </strong>Treatment with Neurokinin B and Senktide significantly increased while SB222200 slightly decrease the seminal vesicles weight, epithelial height and seminal fructose levels as compared to control. Light microscopy revealed increased epithelial height and epithelial folding as compared to control in all Neurokinin B and Senktide treated groups while decreased in SB222200. Effects of various doses of Neurokinin B, Senktide and SB222200 on seminal vesicles weight, epithelial height, seminal fructose levels and histomorphology were reversed when rats were maintained without treatments. Immuno-expression of Neurokinin B shows no change in treatment and reversal groups.</p><p><strong>Conclusion: </strong>Continuous administration of Neurokinin B and Senktide effect positively while SB222200 have detrimental effects on cellular morphology, epithelial height and seminal fructose levels in seminal vesicles. Effects of peptide treatments depicted a reversal towards control group when rats were kept without any treatment.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139511251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Diabetic wound healing is expected to affect 25% of all diabetics, resulting in less severe external factors, economic costs, and less trauma. Topical formulations have been continually improved to achieve a range of amazing properties and have had a significant impact on the management of diabetic wounds. Topical insulin has become one of the most attractive and convenient wound healing techniques due to its excellent biocompatibility, water retention, and therapeutic properties. Multiple versatile topical insulins have been identified and have shown promise over the past few years as they greatly facilitate the management of diabetic wounds as we understand their etiology. The physiological wound healing process repairs damaged tissue and restores skin integrity. For about a century, insulin, a powerful healing agent, and it has been utilized in several clinical and experimental researches research studies to accelerate the healing of various injuries.
{"title":"Diabetic Wound: Pathophysiology, Complications and Treatment Strategies.","authors":"Sunita Chauhan, Monika Gulia, Rahul Pratap Singh, Vikas Jhawat","doi":"10.2174/0113892037276171231016103320","DOIUrl":"10.2174/0113892037276171231016103320","url":null,"abstract":"<p><p>Diabetic wound healing is expected to affect 25% of all diabetics, resulting in less severe external factors, economic costs, and less trauma. Topical formulations have been continually improved to achieve a range of amazing properties and have had a significant impact on the management of diabetic wounds. Topical insulin has become one of the most attractive and convenient wound healing techniques due to its excellent biocompatibility, water retention, and therapeutic properties. Multiple versatile topical insulins have been identified and have shown promise over the past few years as they greatly facilitate the management of diabetic wounds as we understand their etiology. The physiological wound healing process repairs damaged tissue and restores skin integrity. For about a century, insulin, a powerful healing agent, and it has been utilized in several clinical and experimental researches research studies to accelerate the healing of various injuries.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71421455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ARL15 is a member of the RAS superfamily of small GTPases and is associated with several metabolic traits, including increased risk of diabetes, rheumatoid arthritis and lipid metabolism disorders. The ARL15 gene encodes for an uncharacterized small GTP binding protein. Its precise role in human physiology remains unknown, but several genetic association studies have recognized different variants in this gene to be statistically associated with numerous traits and complex diseases. Here, we provided the unique features of ARL15 small G protein, its association with varied metabolic and lifestyle diseases, its function in vesicular and lipid trafficking, and its binding partners. We outlined this protein as a promising and emerging therapeutic target to combat metabolic disorders like cardiovascular diseases, diabetes and rheumatoid arthritis. The review provides a comprehensive description of the current advancements in ARL15 research with a perspective that focused research will position this small GTPase as a viable target for the treatment of rheumatoid arthritis.
{"title":"ARL15 and its Multiple Disease Association: Emerging Functions and Potential Therapeutic Application.","authors":"Manisha Saini, Varnita Anand, Aditya Sharma, Anuj Pandey, Bittianda Kuttapa Thelma, Suman Kundu","doi":"10.2174/1389203724666230915123217","DOIUrl":"10.2174/1389203724666230915123217","url":null,"abstract":"<p><p>ARL15 is a member of the RAS superfamily of small GTPases and is associated with several metabolic traits, including increased risk of diabetes, rheumatoid arthritis and lipid metabolism disorders. The ARL15 gene encodes for an uncharacterized small GTP binding protein. Its precise role in human physiology remains unknown, but several genetic association studies have recognized different variants in this gene to be statistically associated with numerous traits and complex diseases. Here, we provided the unique features of ARL15 small G protein, its association with varied metabolic and lifestyle diseases, its function in vesicular and lipid trafficking, and its binding partners. We outlined this protein as a promising and emerging therapeutic target to combat metabolic disorders like cardiovascular diseases, diabetes and rheumatoid arthritis. The review provides a comprehensive description of the current advancements in ARL15 research with a perspective that focused research will position this small GTPase as a viable target for the treatment of rheumatoid arthritis.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10286952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioconjugation techniques have emerged as powerful tools for enhancing the stability and targeting efficiency of protein and peptide therapeutics. This review provides a comprehensive analysis of the various bioconjugation strategies employed in the field. The introduction highlights the significance of bioconjugation techniques in addressing stability and targeting challenges associated with protein and peptide-based drugs. Chemical and enzymatic bioconjugation methods are discussed, along with crosslinking strategies for covalent attachment and site-specific conjugation approaches. The role of bioconjugation in improving stability profiles is explored, showcasing case studies that demonstrate successful stability enhancement. Furthermore, bioconjugation techniques for ligand attachment and targeting are presented, accompanied by examples of targeted protein and peptide therapeutics. The review also covers bioconjugation approaches for prolonging circulation and controlled release, focusing on strategies to extend half-life, reduce clearance, and design-controlled release systems. Analytical characterization techniques for bioconjugates, including the evaluation of conjugation efficiency, stability, and assessment of biological activity and targeting efficiency, are thoroughly examined. In vivo considerations and clinical applications of bioconjugated protein and peptide therapeutics, including pharmacokinetic and pharmacodynamic considerations, as well as preclinical and clinical developments, are discussed. Finally, the review concludes with an overview of future perspectives, emphasizing the potential for novel conjugation methods and advanced targeting strategies to further enhance the stability and targeting efficiency of protein and peptide therapeutics.
{"title":"Bioconjugation Techniques for Enhancing Stability and Targeting Efficiency of Protein and Peptide Therapeutics.","authors":"Tanuja Bisht, Anupriya Adhikari, Shivanand Patil, Shivang Dhoundiyal","doi":"10.2174/0113892037268777231013154850","DOIUrl":"10.2174/0113892037268777231013154850","url":null,"abstract":"<p><p>Bioconjugation techniques have emerged as powerful tools for enhancing the stability and targeting efficiency of protein and peptide therapeutics. This review provides a comprehensive analysis of the various bioconjugation strategies employed in the field. The introduction highlights the significance of bioconjugation techniques in addressing stability and targeting challenges associated with protein and peptide-based drugs. Chemical and enzymatic bioconjugation methods are discussed, along with crosslinking strategies for covalent attachment and site-specific conjugation approaches. The role of bioconjugation in improving stability profiles is explored, showcasing case studies that demonstrate successful stability enhancement. Furthermore, bioconjugation techniques for ligand attachment and targeting are presented, accompanied by examples of targeted protein and peptide therapeutics. The review also covers bioconjugation approaches for prolonging circulation and controlled release, focusing on strategies to extend half-life, reduce clearance, and design-controlled release systems. Analytical characterization techniques for bioconjugates, including the evaluation of conjugation efficiency, stability, and assessment of biological activity and targeting efficiency, are thoroughly examined. <i>In vivo</i> considerations and clinical applications of bioconjugated protein and peptide therapeutics, including pharmacokinetic and pharmacodynamic considerations, as well as preclinical and clinical developments, are discussed. Finally, the review concludes with an overview of future perspectives, emphasizing the potential for novel conjugation methods and advanced targeting strategies to further enhance the stability and targeting efficiency of protein and peptide therapeutics.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71421552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Skeletal muscle tissue has the critical function of mechanical support protecting the body. In addition, its functions are strongly influenced by the balanced synthesis and degradation processes of structural and regulatory proteins. The inhibition of protein synthesis and/or the activation of catabolism generally determines a pathological state or condition called muscle atrophy, a reduction in muscle mass that results in partial or total loss of function. It has been established that many pathophysiological conditions can cause a decrease in muscle mass. Skeletal muscle innervation involves stable and functional neural interactions with muscles via neuromuscular junctions and is essential for maintaining normal muscle structure and function. Loss of motor innervation induces rapid skeletal muscle fiber degeneration with activation of atrophy-related signaling and subsequent disassembly of sarcomeres, altering normal muscle function. After denervation, an inflammation stage is characterized by the increased expression of pro-inflammatory cytokines that determine muscle atrophy. In this review, we highlighted the impact of some soluble factors on the development of muscle atrophy by denervation.
{"title":"Soluble Factors Associated with Denervation-induced Skeletal Muscle Atrophy.","authors":"Marianny Portal Rodríguez, Claudio Cabello-Verrugio","doi":"10.2174/0113892037189827231018092036","DOIUrl":"10.2174/0113892037189827231018092036","url":null,"abstract":"<p><p>Skeletal muscle tissue has the critical function of mechanical support protecting the body. In addition, its functions are strongly influenced by the balanced synthesis and degradation processes of structural and regulatory proteins. The inhibition of protein synthesis and/or the activation of catabolism generally determines a pathological state or condition called muscle atrophy, a reduction in muscle mass that results in partial or total loss of function. It has been established that many pathophysiological conditions can cause a decrease in muscle mass. Skeletal muscle innervation involves stable and functional neural interactions with muscles <i>via</i> neuromuscular junctions and is essential for maintaining normal muscle structure and function. Loss of motor innervation induces rapid skeletal muscle fiber degeneration with activation of atrophy-related signaling and subsequent disassembly of sarcomeres, altering normal muscle function. After denervation, an inflammation stage is characterized by the increased expression of pro-inflammatory cytokines that determine muscle atrophy. In this review, we highlighted the impact of some soluble factors on the development of muscle atrophy by denervation.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138451166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/0113892037277894231208065403
Jing Zhang, Shujie Yuan, Shujuan Beng, Wenhui Luo, Xiaoqun Wang, Lei Wang, Can Peng
The separation of proteins in biological samples plays an essential role in the development of disease detection, drug discovery, and biological analysis. Protein imprinted polymers (PIPs) serve as a tool to capture target proteins specifically and selectively from complex media for separation purposes. Whereas conventional molecularly imprinted polymer is time-consuming in terms of incubation studies and solvent removal, magnetic particles are introduced using their magnetic properties for sedimentation and separation, resulting in saving extraction and centrifugation steps. Magnetic protein imprinted polymers (MPIPs), which combine molecularly imprinting materials with magnetic properties, have emerged as a new area of research hotspot. This review provides an overview of MPIPs for proteins, including synthesis, preparation strategies, and applications. Moreover, it also looks forward to the future directions for research in this emerging field.
{"title":"Recent Advances in Molecular Imprinting for Proteins on Magnetic Microspheres.","authors":"Jing Zhang, Shujie Yuan, Shujuan Beng, Wenhui Luo, Xiaoqun Wang, Lei Wang, Can Peng","doi":"10.2174/0113892037277894231208065403","DOIUrl":"10.2174/0113892037277894231208065403","url":null,"abstract":"<p><p>The separation of proteins in biological samples plays an essential role in the development of disease detection, drug discovery, and biological analysis. Protein imprinted polymers (PIPs) serve as a tool to capture target proteins specifically and selectively from complex media for separation purposes. Whereas conventional molecularly imprinted polymer is time-consuming in terms of incubation studies and solvent removal, magnetic particles are introduced using their magnetic properties for sedimentation and separation, resulting in saving extraction and centrifugation steps. Magnetic protein imprinted polymers (MPIPs), which combine molecularly imprinting materials with magnetic properties, have emerged as a new area of research hotspot. This review provides an overview of MPIPs for proteins, including synthesis, preparation strategies, and applications. Moreover, it also looks forward to the future directions for research in this emerging field.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139097535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/0113892037272528231030074158
Xianqiong Jiang, Li Gao, Zhilong Li, Yan Shen, Zhi-Hua Lin
Cyclic peptides are polypeptide chains formed by cyclic sequences of amide bonds between protein-derived or non-protein-derived amino acids. Compared to linear peptides, cyclic peptides offer several unique advantages, such as increased stability, stronger affinity, improved selectivity, and reduced toxicity. Cyclic peptide has been proved to have a promising application prospect in the medical field. In addition, this paper mainly describes that cyclic peptides play an important role in anti-cancer, anti-inflammatory, anti-virus, treatment of multiple sclerosis and membranous nephropathy through immunomodulation. In order to know more useful information about cyclic peptides in clinical research and drug application, this paper also summarizes cyclic peptides currently in the clinical trial stage and cyclic peptide drugs approved for marketing in the recent five years. Cyclic peptides have many advantages and great potential in treating various diseases, but there are still many challenges to be solved in the development process of cyclic peptides.
{"title":"Development and Challenges of Cyclic Peptides for Immunomodulation.","authors":"Xianqiong Jiang, Li Gao, Zhilong Li, Yan Shen, Zhi-Hua Lin","doi":"10.2174/0113892037272528231030074158","DOIUrl":"10.2174/0113892037272528231030074158","url":null,"abstract":"<p><p>Cyclic peptides are polypeptide chains formed by cyclic sequences of amide bonds between protein-derived or non-protein-derived amino acids. Compared to linear peptides, cyclic peptides offer several unique advantages, such as increased stability, stronger affinity, improved selectivity, and reduced toxicity. Cyclic peptide has been proved to have a promising application prospect in the medical field. In addition, this paper mainly describes that cyclic peptides play an important role in anti-cancer, anti-inflammatory, anti-virus, treatment of multiple sclerosis and membranous nephropathy through immunomodulation. In order to know more useful information about cyclic peptides in clinical research and drug application, this paper also summarizes cyclic peptides currently in the clinical trial stage and cyclic peptide drugs approved for marketing in the recent five years. Cyclic peptides have many advantages and great potential in treating various diseases, but there are still many challenges to be solved in the development process of cyclic peptides.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138290594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/0113892037287189240122110819
Meixin Li, Yaqi Xue, Lianli Chi, Lan Jin
Background: It has been proven that vasoactive intestinal peptide (VIP) was involved in the pathogenesis of prostate cancer. Cardin et al. found that by an alanine scan, the heparin- binding site on VIP was exactly the same sequence in VIP and its receptor. Therefore, heparin could competitively block the binding of VIP and its receptor. However, the structure-activity relationship between heparin and VIP has not been reported, especially in terms of the sequence and sulfation patterns of heparin oligosaccharides upon binding to VIP.
Objective: A variety of experiments were designed to study the binding process and structure-activity relationship between heparin oligosaccharides and VIP.
Methods: Heparin was enzymatically digested and purified to produce heparin oligosaccharides, and the structures were characterized by NMR. The binding capacity between heparin oligosaccharides and VIP was analyzed by GMSA and ITC experiments. The binding between heparin oligosaccharides and VIP was simulated using a molecular docking program to show the complex. ELISA assay was used to investigate the effect of non-anticoagulant heparin oligosaccharides on the VIP-mediated cAMP/PKA signaling pathway in vitro.
Results: The results indicated that both the length and the sulfation pattern of heparin oligosaccharides affected its binding to VIP. VIP could induce the expression of cAMP at a higher level in PC3 cells, which could be regulated by the interaction of heparin oligosaccharides and VIP.
Conclusion: The binding between heparin oligosaccharides and VIP could block the binding between VIP and its receptor on tumor cells. Downloading the regulation of the expression level of cAMP could possibly further affect the subsequent activation of PKA. These non-anticoagulant heparin oligosaccharides may block the VIP-mediated cAMP/PKA signaling pathway and thus exert their antitumor activity.
{"title":"Heparin Oligosaccharides as Vasoactive Intestinal Peptide Inhibitors via their Binding Process Characterization.","authors":"Meixin Li, Yaqi Xue, Lianli Chi, Lan Jin","doi":"10.2174/0113892037287189240122110819","DOIUrl":"10.2174/0113892037287189240122110819","url":null,"abstract":"<p><strong>Background: </strong>It has been proven that vasoactive intestinal peptide (VIP) was involved in the pathogenesis of prostate cancer. Cardin <i>et al</i>. found that by an alanine scan, the heparin- binding site on VIP was exactly the same sequence in VIP and its receptor. Therefore, heparin could competitively block the binding of VIP and its receptor. However, the structure-activity relationship between heparin and VIP has not been reported, especially in terms of the sequence and sulfation patterns of heparin oligosaccharides upon binding to VIP.</p><p><strong>Objective: </strong>A variety of experiments were designed to study the binding process and structure-activity relationship between heparin oligosaccharides and VIP.</p><p><strong>Methods: </strong>Heparin was enzymatically digested and purified to produce heparin oligosaccharides, and the structures were characterized by NMR. The binding capacity between heparin oligosaccharides and VIP was analyzed by GMSA and ITC experiments. The binding between heparin oligosaccharides and VIP was simulated using a molecular docking program to show the complex. ELISA assay was used to investigate the effect of non-anticoagulant heparin oligosaccharides on the VIP-mediated cAMP/PKA signaling pathway <i>in vitro</i>.</p><p><strong>Results: </strong>The results indicated that both the length and the sulfation pattern of heparin oligosaccharides affected its binding to VIP. VIP could induce the expression of cAMP at a higher level in PC3 cells, which could be regulated by the interaction of heparin oligosaccharides and VIP.</p><p><strong>Conclusion: </strong>The binding between heparin oligosaccharides and VIP could block the binding between VIP and its receptor on tumor cells. Downloading the regulation of the expression level of cAMP could possibly further affect the subsequent activation of PKA. These non-anticoagulant heparin oligosaccharides may block the VIP-mediated cAMP/PKA signaling pathway and thus exert their antitumor activity.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139570050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/0113892037275221240327042353
Kuldeep Singh, Jeetendra Kumar Gupta, Shivendra Kumar, Urvashi Soni
Neurodegenerative disorders, which include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), represent a significant and growing global health challenge. Current therapies predominantly focus on symptom management rather than altering disease progression. In this review, we discuss the major therapeutic strategies in practice for these disorders, highlighting their limitations. For AD, the mainstay treatments are cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists. For PD, dopamine replacement therapies, including levodopa, are commonly used. HD is managed primarily with symptomatic treatments, and reusable extends survival in ALS. However, none of these therapies halts or substantially slows the neurodegenerative process. In contrast, this review highlights emerging research into bioactive peptides as potential therapeutic agents. These naturally occurring or synthetically designed molecules can interact with specific cellular targets, potentially modulating disease processes. Preclinical studies suggest that bioactive peptides may mitigate oxidative stress, inflammation, and protein misfolding, which are common pathological features in neurodegenerative diseases. Clinical trials using bioactive peptides for neurodegeneration are limited but show promising initial results. For instance, hemiacetal, a γ-secretase inhibitor peptide, has shown potential in AD by reducing amyloid-beta production, though its development was discontinued due to side effects. Despite these advancements, many challenges remain, including identifying optimal peptides, confirming their mechanisms of action, and overcoming obstacles related to their delivery to the brain. Future research should prioritize the discovery and development of novel bioactive peptides and improve our understanding of their pharmacokinetics and pharmacodynamics. Ultimately, this approach may lead to more effective therapies for neurodegenerative disorders, moving beyond symptom management to potentially modify the course of these devastating diseases.
神经退行性疾病包括阿尔茨海默病(AD)、帕金森病(PD)、亨廷顿病(HD)和肌萎缩性脊髓侧索硬化症(ALS),是一项日益严峻的全球性健康挑战。目前的疗法主要侧重于症状控制,而不是改变疾病的进展。在这篇综述中,我们将讨论这些疾病的主要治疗策略,并强调其局限性。对于注意力缺失症,主要治疗手段是胆碱酯酶抑制剂和N-甲基-D-天冬氨酸(NMDA)受体拮抗剂。对于帕金森病,常用的是多巴胺替代疗法,包括左旋多巴。HD 主要采用对症治疗,可重复使用的疗法可延长 ALS 患者的生存期。然而,这些疗法都不能阻止或大大减缓神经退行性过程。与此相反,本综述重点介绍作为潜在治疗药物的生物活性肽的新兴研究。这些天然存在或人工合成的分子可与特定的细胞靶点相互作用,潜在地调节疾病进程。临床前研究表明,生物活性肽可减轻氧化应激、炎症和蛋白质错误折叠,这些都是神经退行性疾病的常见病理特征。使用生物活性肽治疗神经退行性疾病的临床试验还很有限,但初步结果很有希望。例如,γ-分泌酶抑制剂肽半乙缩醛通过减少淀粉样蛋白-β的产生,显示出治疗注意力缺失症的潜力,但由于副作用,其开发工作已经中止。尽管取得了这些进展,但仍存在许多挑战,包括确定最佳多肽、确认其作用机制以及克服与将其输送到大脑有关的障碍。未来的研究应优先考虑新型生物活性肽的发现和开发,并提高我们对其药代动力学和药效学的认识。最终,这种方法可能会为神经退行性疾病带来更有效的疗法,超越症状管理的范畴,有可能改变这些毁灭性疾病的病程。
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